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Sickle Cell News for September

Landmark Article in New England Journal of Medicine

Health experts have long believed that sickle cell gene variants, which occur in about 1 in 13 African-Americans, increase the risk of premature death, even when people carry only a single copy of the variant. But health records of nearly 50,000 active-duty U.S. Army soldiers between 2011 and 2014 shows that's not the case, according to a study led by researchers at the Stanford University School of Medicine. People who carry two copies of the sickle cell gene variant have sickle cell disease, which brings a drastically shortened life span of only 40 to 60 years, as well as lifelong bouts of intense pain

In contrast, those carrying just one copy of the gene variant have what's called sickle cell trait. Earlier studies have suggested that the health consequences of sickle cell trait might be dire, including higher mortality from a potentially fatal condition called exertional rhabdomyolysis. ER, which occurs when molecules from the breakdown of muscles end up in the kidneys, has been known to fell football players, often when they are practicing too hard in the hot sun without drinking enough water. (ER is distinct from heat exhaustion, however.) Likewise, ER is a risk for soldiers on active duty.

Yet, in the first-ever longitudinal cohort study of sickle cell trait -- which included African-American soldiers of all ages -- researchers have found they suffered no increase in mortality. Lianne Kurina, PhD, an associate professor of medicine at Stanford, and a team of medical researchers found that having sickle cell trait does not increase the risk of death. A paper describing their findings will be published Aug. 3 in The New England Journal of Medicine. Kurina is senior author. D. Alan Nelson, PhD, PA-C, a postdoctoral scholar at Stanford and former Army medical officer, is the lead author.

Inconclusive studies

Case reports suggesting a connection between sickle cell trait and deaths of individual patients have dominated the medical literature, according to the new study. A paper published in 1987 reported a 2,800 percent increase in the risk of exertion-induced sudden deaths among African-American military recruits thought to have sickle cell trait. But the actual sickle cell status of every individual was not known.

Despite relatively weak evidence, Kurina said, it's been assumed that sickle cell trait increases the risk of death, of exertional rhabdomyolysis and of heat stroke. This assumption has led to mandated screening by organizations such as the Air Force, the Navy and the NCAA. But the American Society for Hematology and other organizations have argued that screening programs raise questions about job discrimination. The Army typically screens only before combat deployment and high-altitude activities, the study said.

For the study, the researchers reviewed the health records of 47,944 African-American soldiers who served on active duty between 2011 and 2014 and for whom sickle cell status was known. The researchers got the health records from the Stanford Military Data Repository data set, which Nelson and Kurina created. The repository includes all digitally recorded health encounters at military medical facilities or civilian institutions, general health information and official records of physical performance and mortality of all active-duty U.S. Army soldiers. The data in the repository are de-identified to protect privacy.

Kurina and her colleagues found that the risk of exertional rhabdomyolysis was only 54 percent higher among African-American soldiers with sickle cell trait than among those without it. A 54 percent increase might sound like a lot, but it's far less than the 300 percent increase caused by some ordinary prescription drugs. And smoking, obesity and increasing age each incur a heightened risk of ER that is about the same as sickle cell trait, the study showed.

Why the difference?

A major reason for the difference between the current study and previous ones, Kurina said, may be better safety for active-duty soldiers. As of 2003, soldiers who are engaged in strenuous exercise are required to drink plenty of fluids, build up to strenuous exercise gradually and take regular rests when it's hot. All of these measures are known to reduce exercise-related fatality rates, regardless of whether individuals have sickle cell trait, the study said.

"Another critical difference between our study and the earlier, population-based studies is that in our study, we knew the sickle cell status of everyone in the population," said Kurina. She and her team looked only at soldiers whose sickle cell status was confirmed by blood tests taken during their years of service, instead of from self-reported sickle cell status or past medical history, as had been done in the other studies.

"The most important thing to come out of this study is the really reassuring news that under conditions of universal precautions against dehydration and overheating, we don't see an elevation in the risk of mortality in people with sickle cell trait," said Kurina. It happens, she noted, that the lead author of the 1987 paper went on to propose and validate the measures adopted by the Army to mitigate dehydration and overheating.

The study's results call into question the need to screen service members with sickle cell trait, especially with better safety precautions during intense exertion, Kurina said.

Sickle Cell Trait, Rhabdomyolysis, and Mortality among U.S. Army Soldiers

D. Alan Nelson, Ph.D., Patricia A. Deuster, Ph.D., Robert Carter, III, Ph.D., Owen T. Hill, Ph.D., Vickee L. Wolcott, Ph.D., and Lianne M. Kurina, Ph.D.
N Engl J Med 2016; 375:435-442 August 4, 2016 DOI: 10.1056/NEJMoa1516257
Studies have suggested that sickle cell trait elevates the risks of exertional rhabdomyolysis and death. We conducted a study of sickle cell trait in relation to these outcomes, controlling for known risk factors for exertional rhabdomyolysis, in a large population of active persons who had undergone laboratory tests for hemoglobin AS (HbAS) and who were subject to exertional-injury precautions.
We used Cox proportional-hazards models to test whether the risks of exertional rhabdomyolysis and death varied according to sickle cell trait status among 47,944 black soldiers who had undergone testing for HbAS and who were on active duty in the U.S. Army between January 2011 and December 2014. We used the Stanford Military Data Repository, which contains comprehensive medical and administrative data on all active-duty soldiers.
There was no significant difference in the risk of death among soldiers with sickle cell trait, as compared with those without the trait (hazard ratio, 0.99; 95% confidence interval [CI], 0.46 to 2.13; P=0.97), but the trait was associated with a significantly higher adjusted risk of exertional rhabdomyolysis (hazard ratio, 1.54; 95% CI, 1.12 to 2.12; P=0.008). This effect was similar in magnitude to that associated with tobacco use, as compared with no use (hazard ratio, 1.54; 95% CI, 1.23 to 1.94; P<0.001), and to that associated with having a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30.0 or more, as compared with a BMI of less than 25.0 (hazard ratio, 1.39; 95% CI, 1.04 to 1.86; P=0.03). The effect was less than that associated with recent use of a statin, as compared with no use (hazard ratio, 2.89; 95% CI, 1.51 to 5.55; P=0.001), or an antipsychotic agent (hazard ratio, 3.02; 95% CI, 1.34 to 6.82; P=0.008).
Sickle cell trait was not associated with a higher risk of death than absence of the trait, but it was associated with a significantly higher risk of exertional rhabdomyolysis. (Funded by the National Heart, Lung, and Blood Institute and the Uniformed Services University of the Health Sciences.)

ATLANTA - A pair of Georgia twins took center stage at the Rio Summer Olympics

They were part of a select group chosen to perform in the opening ceremony. J'son and Ja'kerria Walker are two of only eight American children chosen to stand on the worldwide stage when another Olympic torch was lit in Rio de Janeiro in front of 80,000 spectators and millions more watching around the world.

It's been an emotional journey for J'son Walker. The 12-year-old was diagnosed with a serious form of sickle cell disease in 2005.

Ever since, he's had to travel from Sylvester, Georgia, to Children's Healthcare of Atlanta.

But his family always had the Ronald McDonald House.

Biogen Joins Partnership With CDC Foundation to Develop Longitudinal Data Collection System for Sickle Cell Disease
Effort With CDC to Collect, Analyze and Share Much-needed Sickle Cell Information

ATLANTA, GA--(Marketwired - July 20, 2016) - Sickle cell disease, estimated to affect nearly 100,000 Americans, is the most common inherited blood disorder in the United States. The estimated cost of care for people with sickle cell disease is approximately $1.1 billion dollars annually. The CDC Foundation announced a new partnership in 2015 with the U.S. Centers for Disease Control and Prevention's (CDC) Division of Blood Disorders within the National Center on Birth Defects and Developmental Disabilities and other partners to support the development and operation of a longitudinal data collection system for Americans with sickle cell disease. Biogen is joining this partnership to help address this health problem. Data from the system will provide states, healthcare provider networks and pharmaceutical and insurance companies with the information needed to establish cost-effective practices to help improve and potentially extend the lives of people with sickle cell disease.
"Understanding the clinical history of individuals living with sickle cell disease continues to be of great importance," said Coleen Boyle, Ph.D., M.S.Hyg., director of CDC's National Center on Birth Defects and Developmental Disabilities. "The recent partnership fostered between Biogen and the CDC Foundation will further enable critical support for the collection and study of information leading to advances in sickle cell disease treatment."
Other organizations participating in the partnership include the California Rare Disease Surveillance Program and Pfizer Inc. Although this initial stage of the project will be developed in California, the system will have the capacity to include information on every individual diagnosed with sickle cell disease in the United States.
Data will come from a combination of sources including newborn screening, administrative data sets (for example, hospital discharge, emergency department, and state Medicaid data), medical charts, and may include personal interviews. The information gathered through this system will allow for a better understanding of medical and educational interventions for sickle cell disease, as well as improved patient outcomes over time. The goals of the program are to ensure better care for individuals with sickle cell disease and better data for healthcare providers.
"We are grateful to Biogen for joining this important partnership," said Dr. Judith Monroe, president and CEO of the CDC Foundation. "This longitudinal data collection system will be the first system of its kind for sickle cell disease in the United States."
To learn more about how to support this effort, please contact Laura Angel at the CDC Foundation (

The Haemo-Globe Inn- A Sickle Cell Exhibition at Tanzanian’s largest national exhibition
Sabasaba Fair is the most popular national exhibition in Tanzania. Annually it attracts over 1,000,000 people that visit the 30+ manufacturer’s booth, government departments, and research and higher education institutions.
To tie in with this year’s theme of ‘linking production to the market’, the Sickle Cell Exhibition aimed at engaging with the public more closely by finding practical and hands on activities that would demonstrate Sickle Cells and Haematology as a whole. The exhibition was as well for the Department of Haematology and Blood Transfusion at MUHAS.
As a result, the exhibition featured 3 hands- on activities for the public to be engaged in. These were:-
* Cell morphology: to demonstrate the structures of the difference cells in the body, the public got to see blood slide preparations and then witness first hand on the microscope the different cells including a sickled cell. The aim of this activity was to make the disease ‘real’. That it was not just abstract cells that were being talked about but rather in real sense as part of one’s body.
* Haemocue: the attending public got to have their haemoglobin levels checked. This was especially important for the Sickle Cell individuals that attended the exhibition. It also raised awareness on the importance of blood donation, which is crucial in the management of Sickle Cell Disease.
* Blood Group Testing: in the last 4 days of the exhibition, 76 members of the public had known their blood group. Testing for one’s blood group is not a common practice in Tanzania; in fact it can lead to delays when one needs blood transfusion. On top of trying to help with this problem and linking it again to blood transfusion, blood group testing was essential in highlighting the fact that blood group is an inherited factor just as Sickle Cell Disease is purely an inherited blood disorder.
Together with the hands-on activities, a nurse was handy to give public education and engage on Sickle Cell Disease. This opened a dialogue with the public with regards to Sickle Cell Disease. They got to ask questions about the disease, while we got audience to clear up common myths on SCD.
All in all, the exhibition was a huge success with the people that visited. It was also evident from the exhibition of the need to have a rapid Sickle Cell test as over half of the people that visited the booth asked to know about their sickle cell status.

New websites

Sickle Cell Partners of the Carolinas has launched its new website! Please take a look at []

Take a look around and tell us what you think. We are also beginning a daily blog so look for that and while you’re on the site, register for “Sickle Cell Disease… Let’s Talk About It.” The day conference will be held during Sickle Cell Awareness month. Join us Saturday, September 10, 2016 from 8am to 1pm at Friendship Missionary Baptist Church.


Articles in the medical literature

1. Anal Chem. 2016 Jul 21. [Epub ahead of print]
A Quantitative, Point-of-Care Immunoassay Platform to Guide and Monitor Sickle Cell Disease Therapy.
Yang X, Reavis HD, Roberts CL, Kim JS.
Sickle cell patients often require monthly healthy blood transfusions to treat the many complications of the disease. In this therapy, the clinician lowers the amount of hemoglobin S (HbS) containing red blood cells (RBCs) with healthy normal (hemoglobin A, HbA) blood units. We have developed a point-of-care (POC) quantitative immunoassay for HbS to serve as a diagnostic aid for clinicians providing this life-saving treatment. The test consists of a small-footprint reader and cartridges that quantify the percentage of HbS in a small volume of patient blood. The test reports %HbS values in the range from 0 to 90% that highly correlate (slope 1.03, R2 = 0.97) with currently used central laboratory HPLC systems. The test also shows a 1% limit of blank, 2% limit of detection, and 5% limit of quantitation. The test was also shown to encounter minimal effects from potential interferents. This cost-effective, POC HbS quantitative approach will allow for real-time transfusion monitoring in sickle cell treatment settings, and therefore improve workflow and allow clinicians to quickly make informed therapeutic decisions.
PMID: 27442043 [PubMed - as supplied by publisher]
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3. Child Neuropsychol. 2016 Jul 21:1-18. [Epub ahead of print]
Executive functioning and health-related quality of life in pediatric sickle cell disease.
Allen TM1, Anderson LM1, Rothman JA2, Bonner MJ1,3.
Research consistently indicates that children with sickle cell disease (SCD) face multiple risk factors for neurocognitive impairment. Despite this, no empirical research to date has examined the impact of neurocognitive functioning on quality of life for this pediatric group. Thus, the current study aims to examine the relationship between executive functioning and quality of life in a sample of children with SCD and further explore psychosocial and family/caregiver resources as moderators of this relationship. A total of 45 children with SCD aged 8 to 16 years and their caregivers completed measures of quality of life, behavioral ratings of executive functioning, and psychosocial functioning. Hierarchical linear regression models were utilized to determine the impact of executive functioning on quality of life and further test the interaction effects of proposed moderating variables. Controlling for age, pain, and socioeconomic status (SES), executive functioning was found to significantly predict child- and parent-reported quality of life among youth with SCD. Psychosocial resources of the primary caregiver or family was not found to moderate the relationship between executive functioning and quality of life. These results provide the first empirical evidence that lower executive skills negatively predict quality of life for children with SCD, supporting clinical and research efforts which aim to establish efficacious interventions that target cognitive decrements within this pediatric population.
PMID: 27439898 [PubMed - as supplied by publisher]
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4. J Thromb Haemost. 2016 Jul 19. doi: 10.1111/jth.13416. [Epub ahead of print]
Thrombin generation and cell-dependent hypercoagulability in sickle cell disease.
Whelihan MF1, Lim MY1, Mooberry MJ1, Piegore MG1, Ilich A1, Wogu A2, Cai J2, Monroe DM1,Ataga KI1, Mann KG3, Key NS1,4.

Sickle cell disease (SCD) is a hypercoagulable state with chronic activation of coagulation and an increased incidence of thromboembolic events. However, while plasma pre-thrombotic markers such as TAT and D-dimer are elevated, there is no consensus on whether global assays of thrombin generation in plasma are abnormal in patients with SCD. Based on our recent observation that normal red blood cells (RBCs) contribute to thrombin generation in whole blood, we hypothesized that the cellular components in blood (notably phosphatidylserine-expressing erythrocytes) contribute to enhanced thrombin generation in SCD.
Whole blood and plasma thrombin generation assays were performed on blood samples from 25 SCD patients in a non-crisis, "steady state" and 25 healthy race-matched controls.
Whole blood thrombin generation was significantly elevated in SCD while plasma thrombin generation was paradoxically reduced compared to controls. Surprisingly, whole blood and plasma thrombin generation were both negatively correlated with phosphatidylserine exposure on RBCs. Plasma thrombin generation in the presence of exogenous activated protein C or soluble thrombomodulin revealed deficiencies in the protein C/S anticoagulant pathway in SCD. These global changes were associated with significantly lower plasma protein S activity in SCD that correlated inversely with RBC phosphatidylserine exposure.
Increased RBC phosphatidylserine exposure in SCD is associated with acquired protein S deficiency. In addition, these data suggest a cellular contribution to thrombin generation in SCD (other than RBC phosphatidylserine exposure) that explains the elevated thrombin generation in whole blood. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
PMID: 27430959 [PubMed - as supplied by publisher]
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5. J Pediatr Health Care. 2016 Jul 13. pii: S0891-5245(16)30135-3. doi: 10.1016/j.pedhc.2016.06.005. [Epub ahead of print]
Primary and Secondary Stroke Prevention in Children With Sickle Cell Disease.
Mack AK, Thompson AA.
Children with sickle cell disease (SCD) have numerous acute and chronic complications, including central nervous system (CNS) disease, which can be debilitating over their life span. Recognition of risk factors for CNS disease and overt CNS disease should be properly identified by primary care providers, including physicians, physician assistants, and nurse practitioners. Here, we discuss an emerging and important early indicator of CNS disease in the form of silent cerebral infarcts and review overt stroke in patients with SCD. We also discuss transcranial Doppler ultrasonography, when and how often transcranial Doppler ultrasounds should be performed, and management of abnormal results. Lastly, we review the clinical data for the management and prevention of silent cerebral infarcts and overt stroke in children with SCD.
Copyright © 2016 National Association of Pediatric Nurse Practitioners. Published by Elsevier Inc. All rights reserved.
PMID: 27423528 [PubMed - as supplied by publisher]

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6. Cytotherapy. 2016 Jul 13. pii: S1465-3249(16)30438-8. doi: 10.1016/j.jcyt.2016.06.011. [Epub ahead of print]
Cellular therapy for sickle cell disease.
Abraham A1, Jacobsohn DA2, Bollard CM3.
Sickle cell disease (SCD) is a monogenic red cell disorder affecting more than 300 000 annual births worldwide and leading to significant organ toxicity and premature mortality. Although chronic therapies such as hydroxyurea have improved outcomes, more durable therapeutic and curative options are still being investigated. Newer understanding of the disease has implicated invariant natural killer T cells as a critical immune profile that potentiates SCD. Hence, targeting this cell population may offer a new approach to disease management. Hematopoietic stem cell transplant is a curative option for patients with SCD, but the under-representation of minorities on the unrelated donor registry means that this is not a feasible option for more than 75% of patients. Work in this area has therefore focused on increasing the donor pool and decreasing transplant-related toxicities to make this a treatment option for the majority of patients with SCD. This review focuses on the currently available cell and gene therapies for patients with SCD and acknowledges that newer gene-editing approaches to improve gene therapy efficiency and safety are the next wave of potentially curative approaches.
Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.
PMID: 27421743 [PubMed - as supplied by publisher]

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7. Mol Ther. 2016 Jul 13. doi: 10.1038/mt.2016.148. [Epub ahead of print]
CRISPR/Cas9-mediated correction of the sickle mutation in human CD34+ cells.
Hoban MD1, Lumaquin D1, Kuo CY2, Romero Z1, Long J1,3, Ho M1, Young CS4,5, Mojadidi M1,Fitz-Gibbon S6,7, Cooper AR5, Lill GR1, Urbinati F1, Campo-Fernandez B1, Bjurstrom CF1,Pellegrini M6,7, Hollis RP1, Kohn DB1,8.
Targeted genome editing technology can correct the sickle cell disease (SCD) mutation of the ß-globin gene in hematopoietic stem cells. This correction supports production of red blood cells that synthesize normal hemoglobin proteins. Here, we demonstrate that Transcription Activator-Like Effector Nucleases (TALENs) and the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 nuclease system can target DNA sequences around the sickle-cell mutation in the ß-globin gene for site-specific cleavage and facilitate precise correction when a homologous donor template is co-delivered. Several pairs of TALENs and multiple CRISPR guide RNAs were evaluated for both on-target and off-target cleavage rates. Delivery of the CRISPR/Cas9 components to CD34+ cells led to over 18% gene modification in vitro. Additionally, we demonstrate the correction of the SCD mutation in bone marrow (BM) derived CD34+ hematopoietic stem and progenitor cells (HSPCs) from SCD patients, leading to the production of wild-type hemoglobin. These results demonstrate correction of the sickle mutation in patient-derived CD34+ cells using CRISPR/Cas9 technology.
PMID: 27406980 [PubMed - as supplied by publisher]

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8. Acad Emerg Med. 2016 Jul 12. doi: 10.1111/acem.13048. [Epub ahead of print]
Which Febrile Children with Sickle Cell Disease Need a Chest X-Ray?
Eisenbrown K1, Nimmer M2, Ellison AM3, Simpson P4, Brousseau DC2.

Controversy exists regarding which febrile children with sickle cell disease (SCD) should receive a chest x-ray (CXR). Our goal is to provide data informing the decision of which febrile children with SCD presenting to the emergency department (ED) require a CXR to evaluate for acute chest syndrome (ACS).
Retrospective chart review of children ages 3 months to 21 years with SCD presenting to the ED at one of two academic children's hospitals with fever ≥ 38.5°C between 1/1/10 and 12/31/12. Demographic characteristics, respiratory symptoms, and laboratory results were abstracted. The primary outcome was the presence of ACS. Binary recursive partitioning was performed to determine predictive factors for a diagnosis of ACS.
185 (10%) of 1837 febrile ED visits met ACS criteria. The current NHLBI consensus criteria for obtaining a CXR (shortness of breath, tachypnea, cough, or rales) identified 158 (85%) of ACS cases, while avoiding 825 CXRs. Obtaining a CXR in children with NHLBI criteria or chest pain and in children without those symptoms but with a white blood count (WBC) ≥ 18.75 K/μL or a history of ACS identified 181 (98%), while avoiding 430 CXRs.
Children with SCD presenting to the ED with fever and shortness of breath, tachypnea, cough, rales, or chest pain should receive a CXR due to high ACS rates. A higher WBC or history of ACS in a child without one of those symptoms may suggest the need for a CXR. Prospective validation of these criteria is needed. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
PMID: 27404765 [PubMed - as supplied by publisher]

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9. J Natl Med Assoc. 2016 May;108(2):113-8. doi: 10.1016/j.jnma.2016.04.004. Epub 2016 Jun 9.
Physicians' Perception of Sickle-cell Disease Pain.
Lucchesi F1, Figueiredo MS1, Mastandrea EB1, Levenson JL2, Smith WR2, Jacinto AF3, Citero Vde A4.
The aim of this study was to evaluate the physician's perception of pain experienced by patients with sickle-cell disease (SCD). Pain experiences reported by patients were compared with physicians' perception of the patient's pain, and the treatment decision-making process was evaluated. Fifty-two patient-physician pairs were assessed. Before the clinic visit, the patients completed a 3-item on pain experienced 24 h prior to the visit and the PHQ-9. After the patient visit, the physicians completed a questionnaire assessing their perception of the patient's pain and a questionnaire on the factors taken into consideration when evaluating the patient's pain experience. The physicians rated the patients' pain as more intense than did the patients themselves; and there was agreement between pain intensity measurements (p < 0.05). The physicians' perception was influenced by the pain intensity reported by the patient, results of blood count at the time of the patient visit, and medication availability in the public health services. However, these factors were not predictive of the patient's pain intensity perceived by the physician. Patients' depressive symptoms were not predictive factor of the physicians' perception. Biochemical, genetic and symptomatic characteristics of SCD influenced the physicians' perception of the patient's pain experience, while psychosocial aspects did not.
Copyright © 2016 National Medical Association. Published by Elsevier Inc. All rights reserved.
PMID: 27372471 [PubMed - in process]

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10. J Pediatr Psychol. 2016 Jun 30. pii: jsw061. [Epub ahead of print]
Daily Pain, Physical Activity, and Home Fluid Intake in Pediatric Sickle Cell Disease.
Karlson CW1, Baker AM2, Bromberg MH3, David Elkin T4, Majumdar S5, Palermo TM6.
OBJECTIVES : This study examined the temporal relationship between physical activity, fluid intake, and daily pain in children with sickle cell disease (SCD) with frequent pain.  METHODS : A total of 30 African American children (M age  =  13.9; 53% female; 76.3% type SS) who reported pain more than or equal to once every 2 weeks and their parents completed measures of pain and anxiety/depressive symptoms. Children then completed a daily pain diary and wore a physical activity Actiwatch for 14 days at home.  RESULTS : Contrary to physiological theory-based hypotheses, lower physical activity was associated with greater pain during the same day and the next day. Less pain was associated with greater physical activity the next day. There was no relationship between self-reported home fluid intake and daily pain (p's  <  .05).  CONCLUSIONS : Results lend support for a complex bidirectional relationship between physical activity and daily pain in pediatric SCD, and identify physical activity as a target for future research.
© The Author 2016. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail:

PMID: 27370016 [PubMed - as supplied by publisher]
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12. Lancet. 2016 Jun 18;387(10037):2565-74. doi: 10.1016/S0140-6736(16)00647-4.
Cardiovascular complications and risk of death in sickle-cell disease.
Gladwin MT1.
In sickle-cell disease, a point mutation in the β-globin chain causes haemoglobin to polymerise within erythrocytes during deoxygenation, altering red blood cell rheology and causing haemolysis. Improvements in health infrastructure, preventive care, and clinical treatments have reduced the morbidity and mortality of sickle-cell disease in developed countries. However, as these patients live longer, the chronic effects of sustained haemolytic anaemia and episodic vaso-occlusive events drive the development of end-organ complications. Cardiopulmonary organ dysfunction and chronic kidney injury have a large effect on morbidity and premature mortality, and typically accelerate in the second decade of life. These processes culminate in the development of pulmonary hypertension, left ventricular diastolic heart disease, dysrhythmia, and sudden death. In this Series paper, we review the mechanisms, clinical features, and epidemiology of major cardiovascular complications in patients with sickle-cell disease and discuss how screening and intervention could reduce their incidence.
Copyright © 2016 Elsevier Ltd. All rights reserved.
PMID: 27353687 [PubMed - in process]
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13. Lancet. 2016 Jun 18;387(10037):2554-64. doi: 10.1016/S0140-6736(15)01341-0.
Fetal haemoglobin in sickle-cell disease: from genetic epidemiology to new therapeutic strategies.
Lettre G1, Bauer DE2.
Author information:
• 1Montreal Heart Institute, Montreal, QC, Canada; Université de Montréal, Montreal, QC, Canada. Electronic address:
• 2Boston Children's Hospital, Dana-Farber Cancer Institute, Harvard Medical School and Harvard Stem Cell Institute, Boston, MA, USA. Electronic address: .
Sickle-cell disease affects millions of individuals worldwide, but the global incidence is concentrated in Africa. The burden of sickle-cell disease is expected to continue to rise over the coming decades, adding to stress on the health infrastructures of many countries. Although the molecular cause of sickle-cell disease has been known for more than half a century, treatment options remain greatly limited. Allogeneic haemopoietic stem-cell transplantation is the only existing cure but is limited to specialised clinical centres and remains inaccessible for most patients. Induction of fetal haemoglobin production is a promising strategy for the treatment of sickle-cell disease. In this Series paper, we review scientific breakthroughs in epidemiology, genetics, and molecular biology that have brought reactivation of fetal haemoglobin to the forefront of sickle-cell disease research. Improved knowledge of the regulation of fetal haemoglobin production in human beings and the development of genome editing technology now support the design of innovative therapies for sickle-cell disease that are based on fetal haemoglobin.
Copyright © 2016 Elsevier Ltd. All rights reserved.
PMID: 27353686 [PubMed - in process]
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14. Lancet. 2016 Jun 18;387(10037):2545-53. doi: 10.1016/S0140-6736(16)00145-8.
The intersection between asthma and acute chest syndrome in children with sickle-cell anaemia.
DeBaun MR1, Strunk RC2.
Acute chest syndrome is a frequent cause of acute lung disease in children with sickle-cell disease. Asthma is common in children with sickle-cell disease and is associated with increased incidence of vaso-occlusive pain events, acute chest syndrome episodes, and earlier death. Risk factors for asthma exacerbation and an acute chest syndrome episode are similar, and both can present with shortness of breath, chest pain, cough, and wheezing. Despite overlapping risk factors and symptoms, an acute exacerbation of asthma or an episode of acute chest syndrome are two distinct entities that need disease-specific management strategies. Although understanding has increased about asthma as a comorbidity in sickle-cell disease and its effects on morbidity, substantial gaps remain in knowledge about best management.
Copyright © 2016 Elsevier Ltd. All rights reserved.
PMID: 27353685 [PubMed - in process]
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. Pediatr Nurs. 2016 May-Jun;42(3):113-9, 144.
Depression, Anxiety, and Quality of Life In Children and Adolescents With Sickle Cell Disease.
Graves JK, Hodge C, Jacob E.
The relationships among depression, anxiety, and quality of life were tested, as were the effects of age, gender, and pain frequency on these variables in children (n = 44) and adolescents (n = 31) with sickle cell disease. Participants completed the Revised Child Anxiety and Depression Scale (ROADS) and the Pediatric Quality of Life (PedQL Generic Model). The mean and standard deviation for summary RCADS scores for the majority of participants were below the clinical thresholds of T < 65, indicating low risk for depression (n = 65; 89.3%) and anxiety (n = 70; 93.3%). The subscale scores for the different dimensions of QOL health were a) psychosocial (73.3 ± 15.9), b) emotional (75.0 ± 20.7), c) social (80.8 ± 19.1), d) school functioning (64.0 ≥ 19.8), and e) physical (77.4 ± 17.4). Significant negative correlations were found between mean total quality of life scores and symptoms of a) general anxiety (r = -0.51, p < 0.0001), b) depression (r = -0.66, p < 0.0001), c) obsessive compulsive (r = -0.53, p < 0.0001), d) panic (r = -0.60, p << 0.0001), and e) social phobia (r = -0.57, p < 0.0001). Age and gender did not have significant effects on risk for depression and anxiety or poor QOL. Pain frequency also did not have significant effects on the risk for depression and anxiety. Findings suggest that health care providers need to screen for anxiety and depression, and make referrals for early interventions to improve quality of life and promote school function in youth with sickle cell disease.
PMID: 27468512 [PubMed - in process]

2. Am J Hematol. 2016 Jul 28. doi: 10.1002/ajh.24498. [Epub ahead of print]
< a href="">Patterns of Opioid Use in Sickle Cell Disease.
Han J1,2, Saraf SL2, Zhang X2, Gowhari M2, Molokie RE2,3, Hassan J2, Alhandalous C2, Jain S2,Younge J1, Abbasi T3, Machado RF4, Gordeuk VR2.
Pain, the hallmark complication of sickle cell disease (SCD), is largely managed with opioid analgesics in the United States, but comprehensive data regarding the long-term use of opioids in this patient population is lacking. The pain medication prescription records from a cohort of 203 SCD patients were analyzed. Twenty-five percent were not prescribed opioid medications while 47% took only short-acting opioids, 1% took only long-acting opioids, and 27% took a combination of short-acting and long-acting opioids. The median (interquartile range) daily opioid dose was 6.1 mg (1.7-26.3 mg) of oral morphine equivalents, which is lower than the published opioid use among patients with other pain syndromes. The dose of opioids correlated with the number of admissions due to vaso-occlusive crisis (VOC) (r=0.53, p<0.001). When the patients were grouped into quartiles based on daily dose opioid use, a logistic regression model showed that history of avascular necrosis (AVN) (OR 2.87, 95% CI: 1.37-6.02, p=0.005), 25-OHD levels (OR 0.59, 95% CI: 0.38-0.93, p=0.024) and total bilirubin concentration (OR 0.64, 95% CI: 0.42-0.99, p=0.043) were independently associated with opioid use quartiles. In conclusion, doses and types of opioid medications used by adult SCD patients vary widely. Our findings implicate AVN and lower vitamin D levels as factors associated with higher opioid use. They also suggest an association of higher bilirubin levels, possibly suggesting higher hemolytic rate, with lower opioid use. This article is protected by copyright. All rights reserved.
© 2016 Wiley Periodicals, Inc.
PMID: 27466799 [PubMed - as supplied by publisher]
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3. Community Pract. 2016 Jun;89(6):44-7.
Supported or stigmatised? The impact of sickle cell disease on families.
Keane B, Defoe L.
Caring for a child with a chronic medical condition can be stressful for parents and likely to have an impact on family dynamics. In a low-prevalence region, services to support parents of children with sickle cell disease (SCD) are limited and consequently parents can feel isolated. We explored this issue in a service evaluation, using semi-structured questionnaires to interview twelve families who had a child with SCD. Our analysis outlines the impact that this condition has on family life and the importance that cultural values and perspectives have in learning to deal with the issues involved. We conclude that families would benefit from greater multidisciplinary support on a regular basis.
PMID: 27443031 [PubMed - in process]
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4. BMC Health Serv Res. 2016 Jul 26;16(1):304. doi: 10.1186/s12913-016-1572-6.
< a href="">Newborn screening and prophylactic interventions for sickle cell disease in 47 countries in sub-Saharan Africa: a cost-effectiveness analysis.
Kuznik A1,2,3, Habib AG3, Munube D4, Lamorde M5.
Sickle cell disease (SCD) constitutes a major public health problem in sub-Saharan Africa (SSA). Newborn screening and early subsequent clinical intervention can reduce early mortality and increase life expectancy, but have not been widely implemented in SSA. This analysis assesses the cost-effectiveness of a newborn screening and prophylactic intervention (NSPI) package for SCD in 47 SSA countries.
A lifetime Markov model with annual cycles was built with infants either being screened using isoelectric focusing (IEF) or not screened. Confirmed positive cases received interventions including insecticide-treated mosquito bed nets, folic acid supplementation, prophylactic antimalarial and penicillin therapy, and vaccinations against bacterial infections. Estimates for the local incidence of SCD, the life expectancy of untreated children, the SCD disability weight, and the cost of screening laboratory tests were based on published sources. Among treated infants, the annual probability of mortality until 30 years of age was derived from a pediatric hospital-based cohort. The outcome of interest included a country-specific cost per Disability Adjusted Life Year (DALY) averted.
Of 47 modeled countries in SSA, NSPI is almost certainly highly cost-effective in 24 countries (average cost per DALY averted: US$184); in 10 countries, it is cost-effective in the base case (average cost per DALY averted: US$285), but the results are subject to uncertainty; in the remaining 13, it is most likely not cost-effective. We observe a strong inverse relationship between the incidence rate of SCD and the cost per DALY averted. Newborn screening is estimated to be cost-effective as long as the incidence rate exceeds 0.2-0.3 %, although in some countries NSPI is cost-effective at incidence rates below this range. In total, NSPI could avert over 2.4 million disability adjusted life years (DALYs) annually across SSA.
Using IEF to screen all newborns for SCD plus administration of prophylactic interventions to affected children is cost-effective in the majority of countries in SSA.
PMCID: PMC4962462 Free PMC Article
PMID: 27461265 [PubMed - in process]
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5. Sci Rep. 2016 Jul 27;6:30422. doi: 10.1038/srep30422.
Novel HDAd/EBV Reprogramming Vector and Highly Efficient Ad/CRISPR-Cas Sickle Cell Disease Gene Correction.
Li C1,2, Ding L1,2, Sun CW1,2, Wu LC1,2, Zhou D1,2, Pawlik KM1,2, Khodadadi-Jamayran A2, Westin E1,2, Goldman FD2,3, Townes TM1,2.
CRISPR/Cas enhanced correction of the sickle cell disease (SCD) genetic defect in patient-specific induced Pluripotent Stem Cells (iPSCs) provides a potential gene therapy for this debilitating disease. An advantage of this approach is that corrected iPSCs that are free of off-target modifications can be identified before differentiating the cells into hematopoietic progenitors for transplantation. In order for this approach to be practical, iPSC generation must be rapid and efficient. Therefore, we developed a novel helper-dependent adenovirus/Epstein-Barr virus (HDAd/EBV) hybrid reprogramming vector, rCLAE-R6, that delivers six reprogramming factors episomally. HDAd/EBV transduction of keratinocytes from SCD patients resulted in footprint-free iPSCs with high efficiency. Subsequently, the sickle mutation was corrected by delivering CRISPR/Cas9 with adenovirus followed by nucleoporation with a 70 nt single-stranded oligodeoxynucleotide (ssODN) correction template. Correction efficiencies of up to 67.9% (β(A)/[β(S)+β(A)]) were obtained. Whole-genome sequencing (WGS) of corrected iPSC lines demonstrated no CRISPR/Cas modifications in 1467 potential off-target sites and no modifications in tumor suppressor genes or other genes associated with pathologies. These results demonstrate that adenoviral delivery of reprogramming factors and CRISPR/Cas provides a rapid and efficient method of deriving gene-corrected, patient-specific iPSCs for therapeutic applications.
Free Article
PMID: 27460639 [PubMed - in process]
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6. Pain Res Manag. 2016;2016:3218186. doi: 10.1155/2016/3218186. Epub 2016 Mar 29.
Patient Controlled Analgesia for Adults with Sickle Cell Disease Awaiting Admission from the Emergency Department.
Santos J1, Jones S1, Wakefield D2, Grady J3, Andemariam B1.
Background. A treatment algorithm for sickle cell disease (SCD) pain in adults presenting to a single emergency department (ED) was developed prioritizing initiation of patient controlled analgesia (PCA) for patients awaiting hospitalization. Objectives. Evaluate the proportion of ED visits in which PCA was started in the ED. Methods. A two-year retrospective chart review of consecutive SCD pain ED visits was undertaken. Data abstracted included PCA initiation, low versus high utilizer status, pain scores, bolus opioid number, treatment times, and length of hospitalization. Results. 258 visits resulted in hospitalization. PCA was initiated in 230 (89%) visits of which 157 (68%) were initiated in the ED. Time to PCA initiation was longer when PCA was begun after hospitalization versus in the ED (8.6 versus 4.5 hours, p < 0.001). ED PCA initiation was associated with fewer opioid boluses following decision to admit and less time without analgesic treatment (all p < 0.05). Mean pain intensity (MPI) reduction did not differ between groups. Among visits where PCA was begun in the ED, low utilizers demonstrated greater MPI reduction than high utilizers (2.8 versus 2.0, p = 0.04). Conclusions. ED PCA initiation for SCD-related pain is possible and associated with more timely analgesic delivery.
PMCID: PMC4904609 Free PMC Article
PMID: 27445606 [PubMed - in process]
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Duncan NA, Kronenberger WG, Hampton KC, Bloom EM, Rampersad AG, Roberson CP, Shapiro AD. A validated measure of adherence to antibiotic prophylaxis in children with sickle cell disease. Patient Preference and Adherence 2016;10:983-992.

Sickle Cell Conferences and Events

Sickle Cell Education Day 2016 –Children’s Healthcare of Atlanta, GA
Learning to Live, Love, and Hope with Sickle Cell Disease”
Date: Saturday, September 24, 2016
Time: 9:00 a.m. to 3:00 p.m.
Parking: Courtyard by Marriott, Downtown Decatur
130 Clairemont Avenue
Decatur, GA 30030
Onsite parking is available for $8.
Complimentary parking will be available at the below address:
First Baptist Church of Decatur
308 Clairemont Ave.
Decatur, GA 30030
Registration for this program opens June 22, 2016.
Sickle Cell Partners of the Carolinas presents, Sickle Cell Disease, “Let’s talk about it” day conference Saturday September 10, 2016 9 am to 2 pm Friendship Missionary Baptist Church Conference Center 3400 Beatties Ford Road, Charlotte NC 28216

The Indiana Hemophilia & Thrombosis Center is please to sponsor the annual Sickle Cell-abration Soiree: Celebrating Our Champions to be held at the NCAA Hall of Champions located at 700 W Washington Street Indianapolis, IN on September 17, 2016 from 3:30-9:00 pm.

This year we will be recognizing the sickle cell champions around the state. The event will include education, dinner and entertainment for sickle cell patients and their families.
The event will take place at the

This year we are delighted to have Sonja Banks from the SCDAA as the guest speaker.
For more Information please contact Kisha Hampton at 317-871-0011 ext. 366.
2nd Annual Sickle Cell Disease Symposium: OPIOIDS: THE BIG ELEPHANT IN THE ROOM
Sickle Cell Disease (SCD) is an inherited blood disorder that affects 80,000 people in the US. Sickle red blood cells cause anemia, acute pain, debilitating chronic pain and may lead to a shortened lifespan. This educational program will focus on the multidisciplinary approach to understanding and management of acute and chronic pain in adults living with SCD particularly in light of the current opioid overdose epidemic in the US.

WHEN: Saturday, September 24, 2016 7:00 am – 4:30 pm
The Harris Conference Center 3216 CPCC Harris Campus Dr., Charlotte, NC 28208
For more information or to register, please go to or contact
Tamara Smith-Tillman at 704-512-6534 or
Charlotte AHEC has been authorized by the American Academy of Physician Assistants (AAPA) to designate AAPA Category 1 credits for activities designed primarily for its own learners and other learners who provide care to veterans.

Sickle Cell News for March 2016

Launch of the New Website

The Sickle Cell Information Center website, began in 1997, shortly after internet communication took off. Founded by James R. Eckman , MD, Professor of Hematology and Medical Oncology at the Winship Cancer Institute and Professor of Medicine and Adjunct Professor of Pediatrics in Medical Genetics at Emory University School of Medicine, and Allan Platt , PA-C, MMSc, DFAAPA, Academic Coordinator and Director of Admissions for the Emory University Physician Assistant Program, has been the leading web-based resource for information about sickle cell disease for the past twenty years.

The website is widely used, both throughout the United States and around the globe, regularly averaging 13,500 hits per month, and over 150,000 per year. When Dr. Eckman retired in 2013, after three remarkable decades of work developing the Comprehensive Sickle Cell Program at Grady Health and caring for thousands of patients in the Atlanta area, Allan Platt continued to maintain .

Now, we are pleased to announce that the site has been completely reorganized with a new format, fresh images, and revised text. A collaborative interdisciplinary team of scholars drawn from the Emory Center for Digital Scholarship, the Rollins School of Public Health, and the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta (CHOA) completed this work. Both Dr. Eckman and Allan Platt have been involved in the re-design and we have taken care to leave many familiar aspects of the original website in place so that patients, families, educators, employers, and healthcare providers can access what they need with ease. Generous support for revising the website came from the University Research Committee (URC) of Emory University, from the Emory Center for Digital Scholarship (ECDS) Andrew W. Mellon Foundation Award, and from the Aflac Cancer and Blood Disorders Center. We are grateful for the opportunity made possible by this funding and proud to build on the excellent work started by Eckman and Platt so many years ago.

As always, is committed to providing sickle cell patients and their families and health care providers with professional education, news, research updates and access to up-to-date sickle cell resources worldwide. New features of the site include daily postings of new PubMed articles, links to recent articles from news outlets across the web, additional multilingual resources for patients, families and health care providers, listings of state, national and international sickle cell organizations, and an expanding list of global resources on sickle cell disease. Clinical guidelines are being up updated and will soon be available. The site maintains the privacy of all individuals and no information is gathered. The site is not supported by and does not accept advertising requests. Content and responses are reviewed by the Center Advisory Board. And finally, Information provided on this site is designed to support, not replace, the relationship that exists between a patient/site visitor and his/her physician.

In addition to thanking the institutions that supported this effort, it is important to recognize the work of Mary E. Frederickson, PhD, Clinton H. Joiner, MD, PhD, Peter A. Lane, MD, James R. Eckman, MD, Allan Platt, Allen Tullos, PhD, Wayne H. Morse, Jr., Erin Hecht, PhD, Mekdes Tsegas, Lauren McNaughton, Chase Lovellette, Adrya Stembridge. We also thank the following individuals and institutions for giving us permission to use images and materials from their collections: Oregon State University, Hertz Nazaire, Ellen Weinstein, and the Estate of Twins Seven Seven (Prince Taiwo Olaniyi Oyewale-Toyeje Oyelale Osuntoki).

We hope you enjoy the changes that have been made and the continuity that the site provides. We welcome comments and suggestions for more revisions, so let us know what you think.

News from the website news feed

Our healthcare system abandons adult sickle cell patients

New Resources

Sickle What? Written by Lisa Rose

Price $17.95

- Sickle What? arms patients and parents of newly diagnosed children with the knowledge they need to understand and manage sickle cell disease (SCD). Learn about SCD and how a person gets it in easy-to-understand terms to help parents better understand and be able to explain SCD to a child. Sickle What? shows readers how to read and understand a lab report, what action steps to take when pain occurs and the importance of asking questions and communicating openly with doctors.

To order please contact Daniel at , or 219-922-4868.

Sickle Cell Journal

Price $15.00

-Our Sickle Cell Journal is vital for any sickle cell patient. It allows the patient to journal about their experiences with Sickle Cell, allows the patient to journal about their medications and the different side effects. This is a vital tool for any physician or hospital since they will be able to see the history of the patient’s experience with the disease. To order please contact Daniel at , or 219-922-4868.

Sickle cell in the Medical Literature

1. Exp Biol Med (Maywood). 2016 Mar 29. pii: 1535370216642048. [Epub ahead of print]

Prognostic factors and the response to hydroxurea treatment in sickle cell disease.

Wang WC 1 .


This review describes current considerations in the use of hydroxyurea for the management of sickle cell disease in the context of clinical severity. Randomized trials of hydroxyurea have generally enrolled subjects with increased severity based on frequent vaso-occlusive events. An exception was the BABY HUG study in infants which documented substantial benefit even for asymptomatic subjects. Increasing data indicate that hydroxyurea has a substantial effect on reducing mortality in both adults and children-perhaps the most compelling reason for advocating the drug's widespread use. Although the efficacy of hydroxyurea is mediated primarily through increased erythrocyte fetal hemoglobin and much has been learned about the genomic influences on fetal hemoglobin levels in sickle cell disease, our ability to predict the fetal hemoglobin response to hydroxyurea remains limited; much more work in this area is indicated. The review is concluded with the recommendations of the 2014 NIH Evidence-Based Management of Sickle Cell Disease Expert Panel Report.

© 2016 by the Society for Experimental Biology and Medicine.

PMID: 27026724 [PubMed - as supplied by publisher]

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2. Patient. 2016 Mar 30. [Epub ahead of print]

Cognitive Testing of an Electronic Version of the Faces Pain Scale-Revised with Pediatric and Adolescent Sickle Cell Patients.

Gupta N 1 , Naegeli AN 2 , Turner-Bowker DM 3 , Flood EM 4 , Heath LE 2 , Mays SM 5 , Dampier C 6 .



Patient diaries and pain scales can capture the course and complications of pain managed at home in children. The Faces Pain Scale-Revised (FPS-R) is a validated scale showing reliability in children, but it has not been validated in children with sickle cell disease (SCD).


The purpose of this study was to evaluate comprehension and usability of an electronic modified version of the FPS-R among pediatric patients with SCD.


This was a cross-sectional, qualitative study involving in-person interviews with children/adolescents from the USA and their parents/legal guardians. Interviews involved cognitive debriefing and usability testing of the FPS-R.


In total, 22 children with SCD aged 4-17 years participated. Children aged 4-6 were generally unable to demonstrate clear understanding of the FPS-R and its response scale. Overall, children aged ≥7 years understood the instrument and could complete it on the electronic device, although children aged 7-8 often needed assistance from the parent. Children aged 9-17 years were able to read and complete the instrument independently. Most participants considered the electronic device easy to use.


The FPS-R was shown to be a comprehensible and usable pain measure for children aged 7-17 with SCD and to be beneficial for future clinical studies.

PMID: 27026180 [PubMed - as supplied by publisher]

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3. Exp Biol Med (Maywood). 2016 Mar 27. pii: 1535370216642047. [Epub ahead of print]

A case-control genome-wide association study identifies genetic modifiers of fetal hemoglobin in sickle cell disease.

Liu L 1 , Pertsemlidis A 2 , Ding LH 3 , Story MD 3 , Steinberg MH 4 , Sebastiani P 5 , Hoppe C 6 , Ballas SK 7 , Pace BS 8 .


Sickle cell disease (SCD) is a group of inherited blood disorders that have in common a mutation in the sixth codon of the β-globin (HBB) gene on chromosome 11. However, people with the same genetic mutation display a wide range of clinical phenotypes. Fetal hemoglobin (HbF) expression is an important genetic modifier of SCD complications leading to milder symptoms and improved long-term survival. Therefore, we performed a genome-wide association study (GWAS) using a case-control experimental design in 244 African Americans with SCD to discover genetic factors associated with HbF expression. The case group consisted of subjects with HbF≥8.6% (133 samples) and control group subjects with HbF≤£3.1% (111 samples). Our GWAS results replicated SNPs previously identified in an erythroid-specific enhancer region located in the second intron of theBCL11Agene associated with HbF expression. In addition, we identified SNPs in theSPARC,GJC1,EFTUD2andJAZF1genes as novel candidates associated with HbF levels. To gain insights into mechanisms of globin gene regulation in theHBBlocus, linkage disequilibrium (LD) and haplotype analyses were conducted. We observed strong LD in the low HbF group in contrast to a loss of LD and greater number of haplotypes in the high HbF group. A search of knownHBBlocus regulatory elements identified SNPs 5' of δ-globin located in an HbF silencing region. In particular, SNP rs4910736 created a binding site for a known transcription repressor GFi1 which is a candidate protein for further investigation. Another HbF-associated SNP, rs2855122 in the cAMP response element upstream of Gγ-globin, was analyzed for functional relevance. Studies performed with siRNA-mediated CREB binding protein (CBP) knockdown in primary erythroid cells demonstrated γ-globin activation and HbF induction, supporting a repressor role for CBP. This study identifies possible molecular determinants of HbF production.

© 2016 by the Society for Experimental Biology and Medicine.

PMID: 27022141 [PubMed - as supplied by publisher]

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4. Transfusion. 2016 Mar 28. doi: 10.1111/trf.13548. [Epub ahead of print]

Comparison of automated erythrocytapheresis versus manual exchange transfusion to treat cerebral macrovasculopathy in sickle cell anemia.

Koehl B 1,2 , Sommet J 2,3,4 , Holvoet L 5,6 , Abdoul H 3 , Boizeau P 3 , Ithier G 5,6 , Missud F 5,6 , Couque N 7 , Verlhac S 8 , Voultoury P 9 , Sellami F 9 , Baruchel A 2,5 , Benkerrou M 4,5,6 .



Chronic exchange transfusion is effective for primary and secondary prevention of stroke in children with sickle cell anemia (SCA). Erythrocytapheresis is recognized to be the most efficient approach; however, it is not widely implemented and is not suitable for all patients. The aim of our study was to compare automated exchange transfusion (AET) with our manual method of exchange transfusion and, in particular, to evaluate the efficacy, safety, and cost of our manual method.


Thirty-nine SCA children with stroke and/or abnormal findings on transcranial Doppler were included in the study. We retrospectively analyzed 1353 exchange sessions, including 333 sessions of AET and 1020 sessions of manual exchange transfusion (MET).


Both methods were well tolerated. The median decrease in hemoglobin (Hb)S per session was 21.5% with AET and 18.8% with our manual method (p < 0.0001) with no major increase in red blood cell consumption. Iron overload was well controlled, even with the manual method, with a median (interquartile range) ferritin level of 312 (152-994) µg/L after 24 months of transfusions. The main differences in annual cost relate to equipment costs, which were 74 times higher with the automated method.


Our study shows that continuous MET has comparable efficacy to the automated method in terms of stroke prevention, decrease in HbS, and iron overload prevention. It is feasible in all hospital settings and is often combined with AET successively over time.

© 2016 AABB.

PMID: 27021622 [PubMed - as supplied by publisher]

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5. Hum Gene Ther. 2016 Mar 28. [Epub ahead of print]

Cell and gene therapy for the beta-thalassemias: advances and prospects.

Mansilla-Soto J 1 , Riviere I 2 , Boulad F 3 , Sadelain M 4 .


The beta-thalassemias are inherited anemias caused by mutations that severely reduce or abolish expression of the beta-globin gene. Like sickle cell disease, a related beta-globin gene disorder, they are ideal candidates for performing a genetic correction in patient hematopoietic stem cells (HSCs). The most advanced approach utilizes complex lentiviral vectors encoding the human β-globin gene, as first reported by May et al. in 2000. Considerable progress towards the clinical implementation of this approach has been made in the past five years, based on effective CD34+ cell mobilization and improved lentiviral vector manufacturing. Four trials have been initiated in the US and Europe. Of 16 evaluable subjects, 6 have achieved transfusion independence. One of them developed a durable clonal expansion, which regressed after several years without transformation. While globin lentiviral vectors have so far proven to be safe, this occurrence suggests that powerful insulators with robust enhancer-blocking activity will further enhance this approach. The combined discovery of Bcl11a-mediated γ-globin gene silencing and advances in gene editing are the foundations for another gene therapy approach, which aims to reactivate fetal hemoglobin (HbF) production. Its clinical translation will hinge on the safety and efficiency of gene targeting in true HSCs and the induction of sufficient levels of HbF to achieve transfusion independence. Altogether, the progress achieved over the past 15 years bodes well for finding a genetic cure for severe globin disorders in the next decade.

PMID: 27021486 [PubMed - as supplied by publisher]

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6. Br J Haematol. 2016 Mar 27. doi: 10.1111/bjh.13967. [Epub ahead of print]

Predictors of renal function progression in adults with homozygous sickle cell disease.

Asnani M 1 , Serjeant G 2 , Royal-Thomas T 3 , Reid M 3 .


Longitudinal studies of renal function may improve understanding of the pathophysiological mechanisms underlying sickle cell disease (SCD) nephropathy and may identify possible biological and clinical markers of renal function determined over time. Data from the Jamaica Sickle Cell Cohort Study (JSCCS) were extracted and the glomerular filtration rate (GFR) was estimated using the Chronic Kidney Disease Epidemiological and the SCD specific JSCCS-GFR equations from all adulthood serum creatinine measurements in homozygous SS patients. The other dataset consisted of measured GFR at two times about 13 years apart. Linear mixed model (LMM) regression analyses were conducted to determine predictors of GFR and serum creatinine over time. 191 individuals with SS disease had 867 GFR estimates available. Serum creatinine significantly increased from baseline whereas estimated GFR showed a significant decline. Serum creatinine showed positive association with increasing age, male gender, body mass index and sodium levels. Haemoglobin was a significant negative predictor of estimated GFR in age- and gender-adjusted models. A total of 24 females and 17 males had repeat measurements of their GFR. The mean annual decline in GFR was -3•2 ± 2•83 ml/min/1•73 m2 . Haemoglobin was a significant positive predictor whereas serum creatinine, systolic blood pressure and urinary albumin: creatinine ratio were negative predictors of GFR.

© 2016 John Wiley & Sons Ltd.

PMID: 27018388 [PubMed - as supplied by publisher]

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7. Rheumatology (Oxford). 2016 Mar 27. pii: kew042. [Epub ahead of print]

Haemoglobinopathies and the rheumatologist.

Hughes M 1 , Akram Q 2 , Rees DC 3 , Jones AK 4 .


The haemoglobinopathies are a relatively common, heterogeneous group of inherited conditions that are the result of either a quantitative abnormality (e.g. thalassaemia) or structural [e.g. sickle cell anaemia (SCA)] of the globin part of the haemoglobin molecule. Musculoskeletal (MSK) complications are common in patients with haemoglobinopathies and may affect the whole of the MSK system, in addition to bone, which is the primary site of the disease. Typical MSK complications include painful vaso-occlusive disease and osteomyelitis in SCA and reduced BMD in thalassaemia. Patients may also develop a number of related (e.g. gout) or unrelated rheumatic diseases (e.g. inflammatory arthritis and autoimmune CTDs). Treatment of MSK conditions in patients with haemoglobinopathies may be challenging (e.g. bone marrow suppression from disease-modifying agents) and in particular in SCA, steroid therapy (by any route) may precipitate potentially severe vaso-occlusive complications. Rheumatologists need to be aware of the range of MSK complications, treatment challenges and the need for such patients to be managed as part of a dedicated multidisciplinary team alongside haematology.

© The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: .

PMID: 27018056 [PubMed - as supplied by publisher]

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8. Biol Blood Marrow Transplant. 2016 Mar 22. pii: S1083-8791(16)00152-X. doi: 10.1016/j.bbmt.2016.03.003. [Epub ahead of print]

Allogeneic stem cell transplantation in congenital hemoglobinopathies using tailored busulphan-based conditioning regimen: single center experience.

Zaidman I 1 , Rowe JM 2 , Khalil A 1 , Ben-Arush M 3 , Elhasid R 4 .



Hematopoietic stem cell transplantation (HSCT) is the only proven curative option for patients with hemoglobinopathies, both thalassemia and sickle cell anemia (SCA). Busulphan-based myeloablative conditioning regimen is the standard of care for HSCT in these patients, although increased treatment-related morbidity, including veno-occlusive disease (VOD), has been demonstrated.


A total of 38 pediatric patients, median age was 8 years (range, 6 months-22 years), suffering from hemoglobinopathy were treated at Rambam Medical Center in Haifa, Israel, between 1998 and 2011. Thirty four patients had thalassemia major and four had SCA. The 38 patients underwent 40 HSCT, 34 of which were first transplants and six second transplants. Most of the transplants (32/40) were from matched sibling donors. Sources of stem cells were peripheral blood in 30 transplants, bone marrow in seven transplants, and cord blood in three transplants. All received different customized busulphan-based conditioning regimens tailored by pharmacokinetic analysis of busulphan levels.


Primary engraftment occurred in 37/40 transplants. Neutrophil engraftment (>0.5x109/L) occurred at a median of 15.3 days post-transplantation (range, 10-45 days). Platelet transfusion independence (>20x109/L) occurred at a median of 22.3 days (range, 11-60 days). Five-year overall survival for thalassemia patients after first transplantation was 90.5±5.3%. Five-year thalassemia free survival was 81.7±6.8%. Cumulative incidence of acute GVHD was 17.6%. Rate of grade 3-4 GVHD was 8.8%. Cumulative incidence of chronic GVHD was 23.5%, with 11.8% incidence of extensive chronic GVHD. One patient developed VOD. Full donor chimerism occurred in 36.4% of patients with class I+II thalassemia, compared to 78.6% in class III thalassemia (p=0.049).


Overall survival above 90% in patients undergoing their first transplant was demonstrated using busulphan-based conditioning regimens. The low incidence of VOD was probably due to busulphan area under the curve measurements and dose adjustment.

Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

PMID: 27016193 [PubMed - as supplied by publisher]

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9. Exp Biol Med (Maywood). 2016 Mar 23. pii: 1535370216640385. [Epub ahead of print]

Clinical severity in sickle cell disease: the challenges of definition and prognostication.

Quinn CT 1 .

Author information:


Sickle cell disease (SCD) is a monogenic, yet highly phenotypically variable disease with multisystem pathology. This manuscript provides an overview of many of the known determinants, modifiers, and correlates of disease severity in SCD. Despite this wealth of data, modeling the variable and multisystem pathology of SCD continues to be difficult. The current status of prediction of specific adverse outcomes and global disease severity in SCD is also reviewed, highlighting recent successes and ongoing challenges.

© 2016 by the Society for Experimental Biology and Medicine.

PMID: 27013545 [PubMed - as supplied by publisher]

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10. Semin Hematol. 2016 Apr;53(2):120-8. doi: 10.1053/j.seminhematol.2016.01.001. Epub 2016 Jan 15.

Alternative donor allogeneic hematopoietic cell transplantation for hemoglobinopathies.

Alfraih F 1 , Aljurf M 2 , Fitzhugh CD 3 , Kassim AA 3 .


Allogeneic hematopoietic stem cell transplantation (HSCT) offers a curative therapy for patients with hemoglobinopathies, mainly severe sickle cell disease (SCD) and thalassemia (TM). However, the applicability of HSCT has been limited mainly by donor availability, with a less than 25%-30% of eligible patients having human leukocyte antigen (HLA)-matched sibling donors. Previous outcomes using alternate donor options have been markedly inferior due to increased regimen-related toxicity, transplant-related mortality, graft failure, and graft-versus-host disease (GVHD). Advances in transplant technology, including high-resolution HLA typing, improved GVHD prophylactic approaches with tolerance induction, and better supportive care over the last decade, are addressing these historical challenges, resulting in increasing donor options. Herein, we review alternate donor HSCT approaches for severe SCD and TM using unrelated donors, umbilical cord blood units, or related haploidentical donors. Though this is an emerging field, early results are promising and in selected patients, this may be the preferred option to mitigate against the age-related morbidity and early mortality associated with these disorders.

Copyright © 2016 Elsevier Inc. All rights reserved.

PMID: 27000737 [PubMed - in process]

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Icon for Elsevier Science

11. Clin Trials. 2016 Mar 21. pii: 1740774516636573. [Epub ahead of print]

Addressing challenges of clinical trials in acute pain: The Pain Management of Vaso-occlusive Crisis in Children and Young Adults with Sickle Cell Disease Study.

Nottage KA 1 , Hankins JS 2 , Faughnan LG 3 , James DM 2 , Richardson J 4 , Christensen R 4 , Kang G 5 , Smeltzer M 5 , Cancio MI 2 , Wang WC 2 , Anghelescu DL 6 .



Neuropathic pain is a known component of vaso-occlusive pain in sickle cell disease; however, drugs targeting neuropathic pain have not been studied in this population. Trials of acute pain are complicated by the need to obtain consent, to randomize participants expeditiously while optimally treating pain. We describe the challenges in designing and implementing the Pain Management of Vaso-occlusive Crisis in Children and Young Adults with Sickle Cell Disease Study ( NCT01954927 ), a phase II, randomized, double-blind, placebo-controlled trial to determine the effect of gabapentin for vaso-occlusive crisis.


In the Pain Management of Vaso-occlusive Crisis in Children and Young Adults with Sickle Cell Disease Study, we aim to assess the analgesic effect of gabapentin during vaso-occlusive crisis. Difficulties we identified included avoiding delay of notification of study staff of potential participants which we resolved by automated notification. Concern for rapid randomization and drug dispensation was addressed through careful planning with an investigational pharmacy and a single liquid formulation. We considered obtaining consent during well-visits to avoid the time constraints with acute presentations, but the large number of patients and limited duration that consent is valid made this impractical.


In all, 79% of caregivers/children approached have agreed to participate. The trial is currently active, and enrollment is at 45.8% of that targeted (76 of 166) and expected to continue for two more years. Maintaining staff availability after-hours remains problematic, with 8% of screened patients missed for lack of available staff.


Lessons learned in designing a trial to expedite procedures in the acute pain setting include (1) building study evaluations upon a standard-of-care backbone; (2) implementing a simple study design to facilitate consent and data capture; (3) assuring ample, well-trained study staff; and (4) utilizing technology to automate procedures whenever possible.


This study design has circumvented many of the logistical barriers usually associated with acute pain trials and may serve as a prototype for future studies.

© The Author(s) 2016.

PMID: 27000103 [PubMed - as supplied by publisher]

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12. Am J Public Health. 2016 Mar 21:e1-e3. [Epub ahead of print]

CAREST-Multilingual Regional Integration for Health Promotion and Research on Sickle Cell Disease and Thalassemia.

Knight-Madden J 1 , Romana M 1 , Villaescusa R 1 , Reid M 1 , Etienne-Julan M 1 , Boutin L 1 , Elana G 1 , Elenga N 1 , Wheeler G 1 , Lee K 1 , Nieves R 1 , Jones Lecointe A 1 , Lalanne-Mistrih ML 1 , Loko G 1 , Keclard-Christophe L 1 , Hardy-Dessources MD 1 .

Author information:


Sickle cell disease (SCD) is a significant problem in the Caribbean, where many individuals have African and Asian forebears. However, reliable prevalence data and specific health care programs for SCD are often missing in this region. Closer collaboration between Caribbean territories initiated in 2006 to set up strategies to promote better equity in the health care system for SCD patients led to the formation of CAREST: the Caribbean Network of Researchers on Sickle Cell Disease and Thalassemia. We present the effectiveness of collaborations established by CAREST to promote SCD newborn screening programs and early childhood care, to facilitate health worker training and approaches for prevention and treatment of SCD complications, and to carry out inter-Caribbean research studies. (Am J Public Health. Published online ahead of print March 17, 2016; e1-e3. doi:10.2105/AJPH.2016.303078).

PMID: 26999505 [PubMed - as supplied by publisher]

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13. Transfusion. 2016 Mar 20. doi: 10.1111/trf.13558. [Epub ahead of print]

Effectiveness of red blood cell exchange, partial manual exchange, and simple transfusion concurrently with iron chelation therapy in reducing iron overload in chronically transfused sickle cell anemia patients.

Fasano RM 1,2 , Leong T 3 , Kaushal M 4 , Sagiv E 4 , Luban NL 4,5 , Meier ER 4,5 .



Chronic transfusion therapy (CTT) is indicated for stroke prevention in children with sickle cell anemia (SCA) and is complicated by iron overload and alloimmunization. CTT is performed by simple transfusion (ST), partial manual exchange (PME), or erythrocytapheresis (RCE). Although small case series have demonstrated RCE in combination with iron chelation therapy stabilizes and/or decreases ferritin, there are no reports comparing the effect of ST, PME, and RCE on liver iron concentration (LIC). CTT modality effect on serum ferritin and LIC were compared in SCA patients on iron chelation, with hemoglobin (Hb)S goal of 30%.


Medical records of SCA patients on CTT and deferasirox (≥25 mg/kg/day) were retrospectively reviewed. Mean HbS%, change in ferritin and LIC, and alloimmunization rate were determined for each CTT group.


Twenty-eight patients were included; six crossed over (one from ST to PME, one from ST to PME then to RCE, three from ST to RCE, and one from PME to RCE) to include 36 transfusion modality intervals. Median pretransfusion HbS% levels were 32.7% (ST), 36.2% (PME), and 34.7% (RCE; p = 0.732). Median ferritin changes were +15 (-17 to +45), +38 (+24 to +105), and -91 (-141 to -48) ng/mL/month (p = 0.003), and median LIC changes (available in 22 patient transfusion modality intervals) were +1.3 (-1.6 to +4.3), +2.3 (-6.5 to +8.9), and -5.7 (-10.7 to -0.5) mg/g/year (p = 0.024) in ST, PME, and RCE, respectively. There was no significant difference in alloimmunization rate between ST/PME and RCE groups.


We recommend RCE plus chelation as an effective method for reducing iron overload, while maintaining HbS at 30% to 35%.

© 2016 AABB.

PMID: 26997031 [PubMed - as supplied by publisher]

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14. Indian J Med Res. 2016 Jan;143(1):21-4. doi: 10.4103/0971-5916.178582.

Sickle cell disease in India: A perspective.

Serjeant GR 1 , Ghosh K , Patel J .

Free Article

PMID: 26997009 [PubMed - in process]

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15. Exp Biol Med (Maywood). 2016 Mar 17. pii: 1535370216639737. [Epub ahead of print]

Use of hydroxyurea and phlebotomy in pediatric patients with hemoglobin sickle cell disease.

Summarell CC 1 , Sheehan VA 2 .

Author information:

  • 1 Division of Hematology/Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.


Hydroxyurea is an excellent therapeutic agent for the pharmacological induction of HbF in patients with sickle cell disease (SCD). However, all completed clinical trials of hydroxyurea have excluded patients with hemoglobin SC (HbSC) disease. HbSC differs significantly in pathophysiology from HbSS, as HbC does not sickle, but instead causes cellular dehydration which potentiates sickling of HbS. Many severely affected HbSC patients have been placed on hydroxyurea on a case by case basis, but there are no large scale prospective data on safety or efficacy of hydroxyurea in this subset of patients with SCD. Here, we report a case series of 14 pediatric patients with HbSC treated to maximum tolerated dose (MTD) with hydroxyurea. Those who failed to show clinical improvement after at least six months at MTD were offered phlebotomy in addition to hydroxyurea. Five out of 11 patients with HbSC who achieved MTD failed to demonstrate clinical improvement on hydroxyurea. Of the four placed on dual hydroxyurea and phlebotomy therapy, all showed at least partial clinical improvement. Percent dense red blood cells (%DRBC) were measured via an ADVIA hematology analyzer. A marked rise in percent dense cells preceded clinical complications in three patients. Dual therapy with hydroxyurea and phlebotomy may be an effective approach to patients with HbSC that do not experience improvement with hydroxyurea alone. Monitoring of %DRBC may predict adverse events and aid in assessing hydroxyurea compliance. Large scale clinical trials are needed to evaluate the safety and efficacy of hydroxyurea and hydroxyurea with phlebotomy in patients with HbSC disease.

© 2016 by the Society for Experimental Biology and Medicine.

PMID: 26993671 [PubMed - as supplied by publisher]

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16. Br J Haematol. 2016 Mar 15. doi: 10.1111/bjh.14023. [Epub ahead of print]

A systematic review of the association between depression and health care utilization in children and adults with sickle cell disease.

Jonassaint CR 1 , Jones VL 2 , Leong S 2 , Frierson GM 3 .


Patients with sickle cell disease (SCD) experience a disproportionately high use of health care resources. Several studies have examined depression and other negative mood states as risk factors for increased health care utilization; however, there have been no systematic reviews examining and summarizing this evidence in SCD. The aim of this systematic review, therefore, was to determine whether depression or depressive symptoms are associated with health care utilization among children and adults with SCD. We followed a quantitative systematic review protocol based on the Preferred Reporting Items for Systematic Reviews and Meta- Analyses guidelines and performed a literature search of records from January 1980 to April 2014 using six databases. Empirical studies were eligible if the sample was primarily composed of patients with SCD and included data on depression, mood disorder diagnosis or depressive symptoms and health care utilization. We included 12 studies involving 54 036 unique participants. The prevalence estimates for depression ranged from 2-57%. Seven studies found a significant, or marginally significant, association between depression and utilization while five did not. Patients reporting depression had an estimated 2•8 times greater relative risk of being a high utilizer, and 2•9 versus 1•8 hospitalizations per year on average compared to patients without depression. Overall, depressive symptoms are common in SCD and may increase risk for poor outcomes including health care utilization. The available studies on depression in SCD, however, are limited by small sample sizes, retrospective designs or short follow-up. This systematic review found a modest association between depression and health care utilization in SCD.

© 2016 John Wiley & Sons Ltd.

PMID: 26991317 [PubMed - as supplied by publisher]

Sickle Cell Conferences and Events

Hemoglobinopathy Counselor Training Course will be held on April 7-8, 2016. The two-day course, presented by the Cincinnati Comprehensive Sickle Cell Center, will be held at Cincinnati Children’s Hospital Medical Center. The course registration fee is $150. The deadline to register is March 24, 2016 and registration is limited. For more information, including a course brochure, please email: Registration is also available online at

Conference Name: Integrating Care in Sickle Cell Disease from Pediatrics to Adulthood

Conference Date: Saturday, May 21, 2016

Time: 7:30 am – 4:30pm

Location: St. Jude Children’s Research Hospital

262 Danny Thomas Place

Memphis, TN 38104

Cost: Free

Pre-registration: Required

Register at:

Target Audience: This conference is designed for any practitioner providing treatment to people with sickle cell disease: hematologists, internal medicine physicians, nurses, nurse practitioners, physician assistants, residents, fellows, emergency room physicians, psychologists, and social workers. Adults with sickle cell disease and their significant others are also invited to the conference. CME and Nursing credits will be offered.

Event: Sickle Cell in Focus (SCiF) 2016, National Institutes of Health, Bethesda, Maryland, USA

Date: Thursday 2nd – Friday 3rd June 2016

Venue: Natcher Conference Centre, National Institutes of Health, Bethesda, MD 20894 USA

The 10th Sickle Cell in Focus conference returns to the USA in June 2016. Sickle Cell in Focus is an internationally renowned educational update for sickle cell disease. It attracts a wide audience of clinicians, academics and other healthcare professionals involved in the disease from around the world.

Website: /

To book: Free registration will be opening soob. If you would like to be kept up-to-date, please join the STSTN mailing list by sending an email to:

Contact details: / @STSTNetwork /

Sickle Cell News for March –April 2015

Raising Public Awareness of Sickle Cell and Thalassaemia - New Outreach resources on the United Kingdom Government website and available for public use

The United Kingdom (UK) National Health Service Sickle Cell and Thalassaemia Screening Programme (NHSSCTSP) have published new resources as part of their strategy to improve public understanding of sickle cell disease, thalassaemia and genetic screening.

Education and outreach have been important for the NHSSCTSP because it was the first national genetic screening programme in the UK National Health Service. In 2009, the UK Sickle Cell Society was commissioned to deliver the NHSSCTSP public outreach on sickle cell.  There was a lack of awareness of sickle cell and lots of stigma around the condition particularly in the high risk African and Caribbean communities most at risk of inheriting sickle cell so it was important to educate about sickle cell, testing and associated myths.

These resources now published include a good practice guide for people who commission, fund, deliver and evaluate outreach programmes, an overview of the work delivered and the research underpinning it. The resources capture the learning from years of outreach work. They include a detailed guide that explains the learning, video clips from public events and interviews with service users and people who delivered the outreach. Resources can be accessed from: (For further information contact:

ODEP – Free resource – Work Accommodation Ideas for Sickle Cell Anemia at  A great resource

Track  the new bill in Congress - H.R. 1807 Sickle Cell Disease Research, Surveillance, Prevention, and Treatment Act of 2015 at or

Stem cell transplant resource page:

Local mom starts new career to help sons fight sickle cell disease

Years ago, Tiffany was a school teacher. But after she became a mom, her 9 to 5 changed. “I was a stay at home mom,” Tiffany told 8News Anchor Ava-joye Burnett.

Both of Tiffany’s sons were born with sickle cell disease; the disorder can lead to serious health challenges and excruciating pain.

“You get a child who is crying, ‘Mom, Mom help me, I’m in pain,’ explains Tiffany, “and there is nothing that you can do because they are on morphine and the morphine pump. The doctor or the nurse can possible say, ‘I can’t give your child enough morphine because the pain is immeasurable.’”

The boys are now 12 and 8, trying to live normal lives with a tough disease. Tiffany also has a new career: working at Virginia Blood Services. There’s now a big push here in central Virginia to get more blood donations from African Americans.

“I think a lot of times, people, they don’t see where [their] blood goes, so it’s hard for them to really think and put their heads around that,” says Michelle Westbay, Marketing Director for Virginia Blood Services. “But in the end, you really are supporting lives.” Donations help with blood transfusions, and transfusions help to restore a patient’s body when the disease attacks. There are so many side effects—one of them being stroke—even for kids.

But another major part of the job at Virginia Blood Services is done in labs. Researchers are always looking for rare blood that will go only to patients who desperately need it. In some cases, it’s a patient’s only hope of survival.

Beth Johnson, of Virginia Blood Services, says they handle rare blood in a special way. “Once we find the rare blood, we stash it away so nobody else can have it, except for us and we send it out to re patients who absolutely need it. Aside from working at Virginia Blood Services, Tiffany Dews is also continuing her work outside of the labs, within local communities. Her mission is to get more African Americans to donate blood that could help sickle cell patients—like her two sons.

“No one can see the damage it’s doing to their body as they get older,” Tiffany says. “A lot of times people give up, because no one understands the pain that they go though.”

Santonio Holmes Raises Awareness of Sickle Cell Disease

NFL player Santonio Holmes knows the pain of sickle cell disease. He sees it in his 11-year-old son, T.J., as the boy struggles against the blood disorder that primarily affects people of African descent. A disease that causes intense pain and even life-threatening situations, it’s a tax on the body and the wallet as families often scramble to pay for expensive treatments. Holmes wants to change that. President of the III & Long Foundation, Holmes was in Washington, D.C., recently to meet with members of Congress and health care influencers, advocating for sickle cell research, awareness and treatment.

“As a parent of someone who has been diagnosed with sickle cell, I know how financially expensive and emotionally taxing the hospital visits, bills, treatment and medication can be,” said Holmes. “My goal is to raise awareness and help families that cannot afford the proper treatments by providing grants to organizations that assist these deserving families.”


Sickle cell in the Medical Literature



Thromb Res. 2015 Feb;135 Suppl 1:S46-8. doi: 10.1016/S0049-3848(15)50442-8. Epub 2015 Feb 9.

Sickle cell disease and venous thromboembolism in pregnancy and the puerperium.

Noubouossie D1, Key NS2.



Recent data strongly suggest an increased risk of venous thromboembolism in subjects with sickle cell disease and to a lesser extent, sickle cell trait. However, most studies have been retrospective, case-control or cross-sectional based on data obtained from administrative databases. More data from adequately powered prospective studies that include matched controls are needed to definitely establish the link between venous thromboembolism during pregnancy and sickle hemoglobin disorders. Similarly, there remains a need for properly designed randomized control trials to establish the safety of various hormonal contraceptive methods in women with sickle cell disorders.

© 2015 Elsevier Ltd. All rights reserved.

PMID: 25903535 [PubMed - in process]



Br J Haematol. 2015 Apr 19. doi: 10.1111/bjh.13424. [Epub ahead of print]

Red blood cell transfusions are associated with HLA class I but not H-Y alloantibodies in children with sickle cell disease.

Nickel RS1, Hendrickson JE, Yee MM, Bray RA, Gebel HM, Kean LS, Miklos DB, Horan JT.


Blood transfusions can induce alloantibodies to antigens on red blood cells (RBCs), white blood cells and platelets, with these alloantibodies affecting transfusion and transplantation. While transfusion-related alloimmunization against RBC antigens and human leucocyte antigens (HLA) have been studied, transfusion-related alloimmunization to minor histocompatibility antigens (mHA), such as H-Y antigens, has not been clinically characterized. We conducted a cross-sectional study of 114 children with sickle cell disease (SCD) and tested for antibodies to 5 H-Y antigens and to HLA class I and class II. Few patients had H-Y antibodies, with no significant differences in the prevalence of any H-Y antibody observed among transfused females (7%), transfused males (6%) and never transfused females (4%). In contrast, HLA class I, but not HLA class II, antibodies were more prevalent among transfused than never transfused patients (class I: 33% vs. 13%, P = 0·046; class II: 7% vs. 8%, P = 0·67). Among transfused patients, RBC alloantibody history but not amount of transfusion exposure was associated with a high (>25%) HLA class I panel reactive antibody (Odds ratio 6·8, 95% confidence interval 2·1-22·3). These results are consistent with immunological responder and non-responder phenotypes, wherein a subset of patients with SCD may be at higher risk for transfusion-related alloimmunization.

© 2015 John Wiley & Sons Ltd.

PMID: 25891976 [PubMed - as supplied by publisher]

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Adv Skin Wound Care. 2015 May;28(5):206-10. doi: 10.1097/

Case studies evaluating transdermal continuous oxygen for the treatment of chronic sickle cell ulcers.

Igwegbe I1, Onojobi G, Fadojutimi-Akinsiku MO, Hirsh AM, Park NJ, Yao M, Driver VR.



Refractory leg ulcerations are common in homozygous sickle cell anemia. In this case series, patients were treated with transdermal continuous oxygen therapy (TCOT), based on the hypothesis that oxygen deprivation caused by arteriovenous shunting may be remedied by providing oxygen directly to the wound bed. The authors believe this is the first attempt to treat sickle cell ulcers with TCOT.


Five patients with long histories of recurring sickle cell disease ulcers that would not heal with various conventional and/or other adjunctive wound healing modalities were treated with TCOT. The patients had recurring nonhealing wounds for 30, 21, 20, 20, and 15 years, respectively. All 5 patients healed or showed substantial improvement in the treatment periods of 3 to 36 weeks.


The authors conclude that TCOT may be a novel, effective, and inexpensive modality in treating patients with sickle cell disease ulcers. Improvement was typically noticeable within 2 weeks. Further clinical trials may be considered to evaluate the efficacy of TCOT in sickle cell ulcers.

PMID: 25882658 [PubMed - in process]

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BMC Psychiatry. 2015 Apr 11;15:78. doi: 10.1186/s12888-015-0461-6.

Depression and quality of life in children with sickle cell disease: the effect of social support.

Sehlo MG1,2, Kamfar HZ3.



The majority of available studies have shown that children with sickle cell disease (SCD) have a higher risk of depressive symptoms than those without. The present study aimed to: assess the prevalence of depression in a sample of children with SCD; evaluate the association between disease severity, social support and depression, and the combined and/or singular effect on health-related quality of life (HRQL) in children with SCD; and show the predictive value of social support and disease severity on depression.


A total of 120 children were included in the study, 60 (group I) with SCD and 60 matched, healthy control children (group II). Depression was assessed in both groups using the Children's Depression Inventory (CDI) and the Children's Depression Inventory-Parent (CDI-P). Children with CDI and CDI-P scores of more than 12 were interviewed for further assessment of depression using the Diagnostic Interview Schedule for Children Version IV (DISC-IV). The Pediatric Quality of Life Inventory Version 4.0 Generic Core Scales (PedsQL 4.0) was used to assess HRQL in both groups, and social support was measured with the Child and Adolescent Social Support Scale (CASSS).


Eight (13%) of the 60 children with SCD had CDI and CDI-P scores of more than 12 (CDI mean score 14.50 ± 1.19, CDI-P mean score 14.13 ± 1.12), and were diagnosed as having clinical depression using the diagnostic interview DISC-IV. For group I, HRQL was poor across all PedsQL 4.0 domains in both self- and parent-reports (P < 0.001) compared with group II. A higher level of parent support was a significantly associated with decreased depressive symptoms, demonstrated by lower CDI scores. Better quality of life was shown by the associated higher total PedsQL 4.0 self-scores of children with SCD (B = -1.79, P = 0.01 and B = 1.89, P = 0.02 respectively).


The present study demonstrates that higher levels of parent support were significantly associated with decreased depressive symptoms and better quality of life in children with SCD. Interventions focused on increasing parent support may be an important part of treatment for depression in children with SCD.

PMCID: PMC4394397 Free PMC Article

PMID: 25880537 [PubMed - in process]

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Pak J Med Sci. 2015 Jan-Feb;31(1):203-8. doi: 10.12669/pjms.311.4104.

Mean Platelet Volume can Predict Cerebrovascular Events in Patients with Sickle Cell Anemia.

Celik T1, Unal S2, Ekinci O3, Ozer C4, Ilhan G5, Oktay G6, Arica V7.



The purpose of this study was to determine the impact of mean platelet volume (MPV) on the frequency and severity of vaso-occlusive and cerebrovascular events in patients with sickle cell anemia (SCA).


The 238 cases diagnosed with SCA were evaluated retrospectively with respect to the occurrence of painful crisis for the previous year. The incidence, severity and type of the vaso-occlusive crises of the patients with SCA between March 2010 and March 2011 were recorded. The last MPV values in patients who were free of erythrocyte transfusion for the last three months and who had no current vaso-occlusive crises were evaluated. All the patients were grouped according to the frequency of the crises for the previous year preceding the data collection. Group 1: 1 to 3 crises, Group 2: 4 to 5 and Group 3: 6 or more crises annually.


In accordance with the results obtained during the evaluation of the cases diagnosed with sickle-cell anemia, MPV value was found to be significantly higher in patients with cerebrovascular events. Also MPV values increased with increasing incidence of the crises (r=0.297) (p=0.001).


One of the contributing factors for this clinical heterogeneity may be related to the MPV values in patients with sickle cell anemia. The higher MPV values may be an early predictor of future cerebrovascular events in patients with sickle cell anemia and may require close follow-up and additional measures.

PMCID: PMC4386187 Free PMC Article

PMID: 25878644 [PubMed]

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West Indian Med J. 2015 Mar 5;63(7). doi: 10.7727/wimj.2014.012. [Epub ahead of print]

Clinical Factors Associated with Morbidity and Mortality in Patients Admitted with Sickle Cell Disease.

Galloway-Blake K1, Reid M2, Walters C3, Jaggon J4, Lee MG5.

Author information:



To determine the clinical factors associated with the length of hospitalization and mortality in patients with sickle cell disease (SCD).


All patients with SCD admitted to the medical wards of the University Hospital of the West Indies, Jamaica, over a five-year period, January 1 to December 31, 2010, were reviewed. Data were extracted from hospital charts and comprised demographic and clinical information, investigations, interventions, duration of stay, pathological data and outcomes.


There were 105 patients reviewed; 84% were genotype Hb SS. Females accounted for 59% and males 41%. Overall mean age was 32.5 years (SD 13.7, range 12-66 years). The mean length of hospitalization was 10.2 days (SD 10.9, range 1-84 days). The main admission diagnoses were painful crisis, acute chest syndrome, severe anaemia, sepsis, hepatic sequestration, congestive cardiac failure and renal failure. The mean value for the following laboratory investigations were: haemoglobin 7.7 g/dL (SD 2.8), total white blood cell count 21.7 × 109/L (SD 14.2), platelet count 320 × 109/L (SD 191.9), blood urea 9.8 mmol/L (SD 11.9) and serum creatinine 198 umol/L (SD 267.9). Medical interventions included: blood transfusions in 20.9%, 55% received antibiotics and 74% received narcotic analgesia. There were 40 deaths with four autopsies done. The mortality rate for SCD was 38%. There were 189 repeat SCD admissions.


Sickle cell disease still carries a high morbidity and mortality in patients admitted to hospital. Recurrent admissions are a concern, as they impact on patient's morbidity and quality of life.

PMID: 25867578 [PubMed - as supplied by publisher]

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Br J Haematol. 2015 Apr 9. doi: 10.1111/bjh.13447. [Epub ahead of print]

Estimated pulmonary artery systolic pressure and sickle cell disease: a meta-analysis and systematic review.

Caughey MC1, Poole C, Ataga KI, Hinderliter AL.

Author information:

·  1Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.


Many studies report estimated pulmonary artery systolic pressure (ePASP) in patients with sickle cell disease (SCD) screened by echocardiography. To better understand the prevalence and outcomes of elevated ePASP in clinically stable SCD patients, we conducted a random-effects meta-analysis. A total of 45 studies, representing 15 countries and including 6109 individuals, met our inclusion criteria. In most (70%) studies, elevated ePASP was defined by a tricuspid regurgitant velocity of 2·5 m/s. The prevalence of elevated ePASP was 21% (17-26%) in children and 30% (26-35%) in adults. After adjustment for sex, SCD genotype, haemoglobin, hydroxycarbamide (hydroxyurea) treatment, country and publication year, age remained associated with elevated ePASP, yielding a 12% (0·4-23%) higher adjusted prevalence in adults. Few studies reported 6-min walk tests or mortality outcomes, and estimates were highly heterogeneous. In random effects meta-analyses, patients with elevated ePASP walked an estimated 30·4 (6·9-53·9) metres less than those without elevated ePASP and had an associated mortality hazard ratio of 4·9 (2·4-9·7).

© 2015 John Wiley & Sons Ltd.

PMID: 25854714 [PubMed - as supplied by publisher]

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Physiol Rep. 2015 Apr;3(4). pii: e12338. doi: 10.14814/phy2.12338.

Reduced fitness and abnormal cardiopulmonary responses to maximal exercise testing in children and young adults with sickle cell anemia.

Liem RI1, Reddy M2, Pelligra SA2, Savant AP3, Fernhall B4, Rodeghier M5, Thompson AA2.



Physiologic contributors to reduced exercise capacity in individuals with sickle cell anemia (SCA) are not well understood. The objective of this study was to characterize the cardiopulmonary response to maximal cardiopulmonary exercise testing (CPET) and determine factors associated with reduced exercise capacity among children and young adults with SCA. A cross-sectional cohort of 60 children and young adults (mean 15.1 ± 3.4 years) with hemoglobin SS or S/β(0) thalassemia and 30 matched controls (mean 14.6 ± 3.5 years) without SCA or sickle cell trait underwent maximal CPET by a graded, symptom-limited cycle ergometry protocol with breath-by-breath, gas exchange analysis. Compared to controls without SCA, subjects with SCA demonstrated significantly lower peak VO2 (26.9 ± 6.9 vs. 37.0 ± 9.2 mL/kg/min, P < 0.001). Subjects demonstrated slower oxygen uptake (ΔVO2/ΔWR, 9 ± 2 vs. 12 ± 2 mL/min/watt, P < 0.001) and lower oxygen pulse (ΔVO2/ΔHR, 12 ± 4 vs. 20 ± 7 mL/beat, P < 0.001) as well as reduced oxygen uptake efficiency (ΔVE/ΔVO2, 42 ± 8 vs. 32 ± 5, P < 0.001) and ventilation efficiency (ΔVE/ΔVCO2, 30.3 ± 3.7 vs. 27.3 ± 2.5, P < 0.001) during CPET. Peak VO2 remained significantly lower in subjects with SCA after adjusting for age, sex, body mass index (BMI), and hemoglobin, which were independent predictors of peak VO2 for subjects with SCA. In the largest study to date using maximal CPET in SCA, we demonstrate that children and young adults with SCA have reduced exercise capacity attributable to factors independent of anemia. Complex derangements in gas exchange and oxygen uptake during maximal exercise are common in this population.

© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

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PMID: 25847915 [PubMed]

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Cochrane Database Syst Rev. 2015 Apr 6;4:CD004448. [Epub ahead of print]

Phytomedicines (medicines derived from plants) for sickle cell disease.

Oniyangi O1, Cohall DH.

Author information:

·  1Paediatrics Department, National Hospital, Plot 132 Central District (Phase II), PMB 425 Garki, Abuja, Nigeria.



Sickle cell disease, a common recessively inherited haemoglobin disorder, affects people from sub-Saharan Africa, the Middle East, Mediterranean basin, Indian subcontinent, Caribbean and South America. It is associated with complications and a reduced life expectancy. Phytomedicines (medicine derived from plants in their original state) encompass many of the plant remedies from traditional healers which the populations most affected would encounter. There has been little systematic appraisal of their benefits. This is an update of a Cochrane Review first published in 2010 and updated in 2013.


To assess the benefits and risks of phytomedicines in people with sickle cell disease of all types, of any age, in any setting.


We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, the International Standard Randomized Controlled Trial Number Register (ISRCTN) and the Allied and Complimentary Medicine Database (AMED).Dates of most recent searches: Haemoglobinopathies Trials Register: 13 October 2014; ISRCTN: 17 January 2015; AMED: 20 January 2015.


Randomized or quasi-randomized trials with participants of all ages with sickle cell disease, in all settings, comparing the administration of phytomedicines, by any mode to placebo or conventional treatment, including blood transfusion and hydroxyurea.


Both authors independently assessed trial quality and extracted data.


Two trials (182 participants) and two phytomedicines Niprisan® (also known as Nicosan®) and Ciklavit® were included. The Phase IIB (pivotal) trial suggests that Niprisan® was effective in reducing episodes of severe painful sickle cell disease crisis over a six-month period. It did not affect the risk of severe complications or the level of anaemia. No serious adverse effects were reported. The single trial of Cajanus cajan (Ciklavit®) reported a possible benefit to individuals with painful crises, and a possible adverse effect (non-significant) on the level of anaemia.


While Niprisan® appeared to be safe and effective in reducing severe painful crises over a six-month follow-up period, further trials are required to assess its role in the management of people with sickle cell disease and the results of its multicentre trials are awaited. Currently no conclusions can be made regarding the efficacy of Ciklavit®. Based on the published results for Niprisan® and in view of the limitations in data collection and analysis of both trials, phytomedicines may have a potential beneficial effect in reducing painful crises in sickle cell disease. This needs to be further validated in future trials. More trials are required on the safety and efficacy of phytomedicines used in managing sickle cell disease.

PMID: 25844571 [PubMed - as supplied by publisher]

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Creat Nurs. 2015;21(1):38-46.

Cognitive behavioral therapy in patients with sickle cell disease.

Daniels S.



Sickle cell disease (SCD) is an inherited autosomal recessive disorder. In the United States, most individuals with SCD are African Americans, with an incidence of 1 in 400 to 1 in 500 live births. SCD is a lifelong disorder with no known cure.


SCD causes anemia, frequent painful episodes, and reduced life expectancy. The most disturbing clinical problem associated with SCD is severe pain episodes, the most common reason for hospitalization. Pharmacological interventions have been the mainstream for treatment; however, psychological interventions such as cognitive behavioral therapy (CBT) may complement current medical treatment, leading to better coping and overall improved quality of life.


In a quasi-experimental one-group pretest-posttest study, 9 African American individuals with SCD completed 3 weekly educational sessions learning CBT methods.


Participants demonstrated increased frequency of use of CBT methods post-intervention, including diverting attention, coping self-statements, and behavioral activities, leading to better pain control. However, quality of life and role limitation did not show significant improvement.


CBT may be beneficial to those suffering from SCD when combined with conventional treatment options; however, there are still barriers to incorporating psychological interventions into practice.


CBT shows promise for individuals with chronic conditions such as SCD, but more investigation into its efficacy is needed with larger sample sizes over longer periods of time.

PMID: 25842524 [PubMed - indexed for MEDLINE]

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J Pain. 2015 Apr 1. pii: S1526-5900(15)00603-3. doi: 10.1016/j.jpain.2015.03.010. [Epub ahead of print]

The Effect of Sleep Continuity on Pain in Adults with Sickle Cell Disease.

Moscou-Jackson G1, Finan PH2, Campbell CM2, Smyth JM3, Haythornthwaite JA2.



This analysis examined the influence of quantifiable parameters of daily sleep continuity, primarily sleep duration and sleep fragmentation, on daily pain in adults with Sickle Cell Disease (SCD). Seventy-five adults with SCD completed baseline psychosocial measures and daily morning (sleep) and evening (pain) diaries over a three-month period. Mixed-effect modeling was used to examine daily between- and within-subjects effects of sleep continuity parameters on pain, as well as the synergistic effect of sleep fragmentation and sleep duration on pain. Results revealed nights of shorter sleep duration and time in bed, increased fragmentation, and less efficient sleep (relative to one's own mean) were followed by days of greater pain severity. Further, the analgesic benefit of longer sleep duration was attenuated when sleep fragmentation was elevated. These results suggest that both the separate and combined effects of sleep duration and fragmentation should be considered in evaluating pain in adults with SCD.


Subjective parameters of sleep continuity (e.g. sleep duration, fragmentation, and efficiency) predict clinical pain in individuals with SCD. Additionally, sleep duration should not be considered in isolation and its association with pain may be qualified by sleep fragmentation. Research and practice should include assessments of both when addressing pain severity.

Copyright © 2015 American Pain Society. Published by Elsevier Inc. All rights reserved.

PMID: 25842346 [PubMed - as supplied by publisher]

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Pediatr Emerg Care. 2015 Apr 1. [Epub ahead of print]

Improving Quality of Care for Sickle Cell Patients in the Pediatric Emergency Department.

Lin SM1, Strouse JJ, Whiteman LN, Anders J, Stewart RW.

Author information:

·  1From the *Department of Medicine, and †Department of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, MD.



The aim of this study was to identify the factors associated with delays in treatment of sickle pain crisis in the pediatric emergency department with the goal of discerning whether earlier pain management is correlated with better clinical outcome.


This retrospective study examined data collected from clinical records of patients, aged 21 years or younger, who was treated for sickle cell pain crisis between January and June 2012. Demographic and clinical characteristics were extracted from electronic records, as well as time of registration, triage, initial pain assessment, analgesic administration, and pain reassessment.


A total of 160 sickle cell pain crises visits by 67 unique patients were identified. Opiates were the most common initial pain medication prescribed and administered. The mean time to initial analgesic administration and pain reassessment was 89 and 60 minutes, respectively. Patients with orders for imaging studies experienced significant delays in time to initial analgesic medication and pain reassessment. In addition, higher triage pain score correlated with shorter time to first dose of pain medication. However, age, sex, and final disposition did not affect time to administration of analgesic medications. Earlier pain management resulted in shorter ED length of stay for all patients regardless of disposition. However, earlier pain management did not affect the total length of hospitalization for patients admitted to the inpatient services.


Pediatric patients with sickle cell pain crises experienced significant delays to initial analgesic medication. A standardized approach to pain management may improve ED management of SCD crises.

PMID: 25834959 [PubMed - as supplied by publisher]

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Adv Ther. 2015 Apr 2. [Epub ahead of print]

A Biopsychosocial Model for the Management of Patients With Sickle-Cell Disease Transitioning to Adult Medical Care.

Crosby LE1, Quinn CT, Kalinyak KA.


The lifespan of patients with sickle-cell disease (SCD) continues to increase, and most affected individuals in high-resource countries now live into adulthood. This necessitates a successful transition from pediatric to adult health care. Care for transitioning patients with SCD often falls to primary care providers who may not be fully aware of the many challenges and issues faced by patients and the current management strategies for SCD. In this review, we aim to close the knowledge gap between primary care providers and specialists who treat transitioning patients with SCD. We describe the challenges and issues encountered by these patients, and we propose a biopsychosocial multidisciplinary approach to the management of the identified issues. Examples of this approach, such as transition-focused integrated care models and quality improvement collaboratives, with the potential to improve health outcomes in adulthood are also described.

PMID: 25832469 [PubMed - as supplied by publisher]

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Hemoglobin. 2015 Apr 1:1-7. [Epub ahead of print]

Usability and Feasibility of an mHealth Intervention for Monitoring and Managing Pain Symptoms in Sickle Cell Disease: The Sickle Cell Disease Mobile Application to Record Symptoms via Technology (SMART).

Jonassaint CR1, Shah N, Jonassaint J, De Castro L.

Author information:

·  1School of Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania , USA .


Patients with sickle cell disease frequently experience severe pain events that lead to unplanned healthcare utilization. Mobile health tools (mHealth) may help prevent these events by providing remote monitoring and self-management support. This article describes the feasibility of the Sickle cell disease Mobile Application to Record symptoms via Technology (SMART), an mHealth app developed to help sickle cell disease patients monitor and manage their day-to-day symptoms. Fifteen patients recorded their pain intensity using a paper visual analog scale (VAS) and then repeated this measurement using an electronic VAS pain measure on SMART. Patients continued using SMART to record clinical symptoms, pain intensity, location and perceived severity, and treatment strategies for at least 28 days. Patient median age was 29 years (range 16-54); 60.0% were male. There was a high intraclass correlation between pain measurements entered on the paper VAS and SMART on the iPhone and the iPad We found a strong association between patient perceived pain severity and pain intensity entries using SMART (b = 1.71; p < 0.01). Daily compliance with SMART entries was a mean 75.0%, with a high of 85.7% in week 1 and low of 57.9% in week 4; however, one-third (n = 5) of the patients were 100.0% compliant even in week 4. Patients who were over age 35 or used an iPad for the study had the highest compliance rates. This study showed that SMART is a useable and feasible method for monitoring daily pain symptoms among adolescents and adults with sickle cell disease-related pain.

PMID: 25831427 [PubMed - as supplied by publisher]

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Blood. 2015 Mar 30. pii: blood-2014-09-551564. [Epub ahead of print]

How I treat acute strokes and long-term management in sickle cell disease.

Kassim AA1, Galadanci NA2, Pruthi S3, DeBaun MR4.



Neurological complications are a major cause of morbidity and mortality in sickle cell disease. In children with sickle cell anemia, routine use of transcranial Doppler screening coupled with regular blood transfusion therapy has decreased the prevalence of overt stroke from approximately 11% to 1%. Limited evidence is available to guide acute and chronic management of individuals with sickle cell disease and strokes. Current management strategies are based primarily on single arm clinical trials and observational studies, coupled with principles of neurology and hematology. Initial management of a focal neurological deficit includes evaluation by a multi-disciplinary team (a hematologist, neurologist, neuroradiologist and transfusion medicine specialist); prompt neuro-imaging, and an initial blood transfusion (simple followed immediately by an exchange transfusion or only exchange transfusion), is recommended if the hemoglobin is > 4 gm/dL and < 10 gm/dL. Standard therapy for secondary prevention of strokes and silent cerebral infarcts includes regular blood transfusion therapy and in selected cases, hematopoietic stem cell transplantation. A critical component of the medical care following an infarct is cognitive and physical rehabilitation. We will discuss our strategy of acute and long-term management of strokes in sickle cell disease.

Copyright © 2015 American Society of Hematology.

PMID: 25824688 [PubMed - as supplied by publisher]

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Br J Haematol. 2015 Mar 30. doi: 10.1111/bjh.13348. [Epub ahead of print]

Guideline on the management of acute chest syndrome in sickle cell disease.

Howard J1, Hart N, Roberts-Harewood M, Cummins M, Awogbade M, Davis B.

Author information:

·  1Department of Haematology, Guy's and St Thomas' NHS Foundation Trust, London, UK.

PMID: 25824256 [PubMed - as supplied by publisher]

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Blood. 2015 Mar 25. pii: blood-2014-09-551887. [Epub ahead of print]

How I treat priapism.

Anele UA1, Le BV1, Resar LM2, Burnett AL3.

Author information:

·  1The James Buchanan Brady Urological Institute and Department of Urology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States;

·  2Division of Hematology, Department of Medicine, Department of Oncology, and Institute for Cellular Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States.

·  3The James Buchanan Brady Urological Institute and Department of Urology, The Johns Hopkins University School of Medicine, Baltimore, MD, United States;


Priapism is a disorder of persistent penile erection unrelated to sexual interest or desire. This pathologic condition, specifically the ischemic variant, is often associated with devastating complications, notably erectile dysfunction. Because priapism demonstrates high prevalence in patients with hematological disorders, most commonly sickle cell disease (SCD), there is significant concern for its sequelae in this affected population. Thus, timely diagnosis and management are critical for the prevention or at least reduction of cavernosal tissue ischemia and potential damage consequent to each episode. Current guidelines and management strategies focus primarily on reactive treatments. However, an increasing understanding of the molecular pathophysiology of SCD-associated priapism has led to the identification of new potential therapeutic targets. Future agents are being developed and explored for use in the prevention of priapism.

Copyright © 2015 American Society of Hematology.

PMID: 25810489 [PubMed - as supplied by publisher]

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Pediatr Blood Cancer. 2015 Feb 7. doi: 10.1002/pbc.25439. [Epub ahead of print]

Allogeneic donor availability for hematopoietic stem cell transplantation in children with sickle cell disease.

Justus D 1, Perez-Albuerne E , Dioguardi J , Jacobsohn D , Abraham A .


Hematopoietic stem cell transplant is curative of sickle cell disease (SCD) but limited by donor availability. Searches for 85 patients with SCD without matched sibling donors from 2009-2013 using modern techniques (allele-level HLA matching for unrelated donors and higher total nucleated cell doses for umbilical cord blood (UCB)) showed potential match probabilities of 20% for 8/8 HLA-matched unrelated donors, 84% for 7/8 donors, and 97% for two 4-6/6 UCBs suitable for ex-vivo expanded/double cord transplant. Searches performed by age 43 months would have a 90% chance of finding a suitable 5-6/6 UCB. Pediatr Blood Cancer © 2015 Wiley Periodicals, Inc.


Sickle Cell Conferences and Events

 Sickle Cell in Focus (SCiF), London, UK

Date:  Monday 15 – Tuesday 16 June 2015

Venue: The Light @ Euston, Friends House, 173-177 Euston Road, London, NW1 2BJ, UK


The 9th Sickle Cell in Focus returns to London in 2015. Professor Swee Lay Thein and Dr John Tisdale have once again planned an excellent programme. This year, in addition to updating on the emerging and current clinical and management issues related to sickle cell disease, there will be a focus on new drug developments, clinical trials and new genetics. 


Sickle Cell in Focus has become a internationally renowned educational update for sickle cell disease.  It attracts a wide audience of clinicians, academics and other healthcare professionals involved in the disease from around the world.


To book: Online booking will be open soon.  If you would like to be kept up-to-date, please join the STSTN mailing list by sending an email to:


Contact details:  / + 44 (0) 20 7848 5441 / @STSTNetwork


SCDAA 43rd Annual Convention

September 23 - 26, 2015
Hilton - Baltimore, MD



Listserv  address to join or leave

Sickle Cell News for January 2015

Care Plans to Reduce Healthcare Utilization in Sickle Cell Disease

Published Online: at

Surabhi Dangi-Garimella, PhD

While innovations in drug development improve patient health, care management plans in hospitals and academic health institutes are evolving simultaneously to allow for better patient care at reduced costs. That was the conclusion of presenters at a Health Services and Outcomes Research session on sickle cell disease (SCD) management, part of the 56th Meeting of the American Society of Hematology, held in San Francisco, California, December 6-9, 2014.

SCD, a commonly inherited blood disorder resulting from abnormal hemoglobin, is associated with lifelong disabilities and can reduce life expectancy. The disease affects between 90,000 and 100,000 people in the United States,1 and a study published in 2009 in the American Journal of Hematology estimated that the annual cost of medical care alone for these patients exceeds $1.1 billion.2

Jane S. Hankins, MD, MS, associate professor, St. Jude Children’s Research Hospital, presented the model being evaluated at her institute to manage the transition of pediatric patients with SCD into adult care while avoiding the overutilization of healthcare.

- See more at:

Announcing Sickle Cell Branch and New Lasker Fellow in DIR
It is with great pleasure that I announce that a Sickle Cell Branch is being established in the DIR.  As you may have heard from Dr. Gibbons during his address at the NHLBI Awards Ceremony, this is a priority area for the NHLBI and is aligned with its mission.  We are very fortunate that Dr. Swee Lay Thein, M.B,B.S; FRCP, D.Sc, an international expert in sickle cell disease, will be joining the DIR as Senior Investigator in the Spring of 2015 to lead this new branch.  Dr. Thein is coming to us from King’s College, London where she -has-- is currently a Professor of Molecular Hematology and the head of the Division of Gene and Cell Therapy.   Dr. Thein was educated and received her medical training in both Malaysia and the UK, and is a member of several Sickle Cell Disease networks globally.  Over the course of her career she has made major contributions to our understanding of sickle cell phenotypes as well as pioneered new treatment strategies in clinical trials.

Joining Dr. Thein in the Sickle Cell Branch will be a newly awarded Lasker Clinical Research Scholar, Dr. Hans Ackerman, M.D., D.Phil, M.Sc.  Dr. Ackerman comes to us from NIAID where he was an Assistant Clinical Investigator.  He received his M.D. from Harvard Medical School and his D.Phil from Oxford.  Dr. Ackerman’s team is studying the vascular complications associated with sickle cell disease and malaria. Also joining this newly created Branch will be Drs. John Tisdale, James Taylor, and Courtney Fitzhugh.


Sickle cell: Stopping kids' silent strokes

About 100,000 Americans have sickle cell disease -- a genetic condition where the body's red blood cells are deformed, clogging up arteries, and causing pain, disability or major stroke, even in kids. Patients who suffer strokes often have regular blood transfusions to prevent a repeat attack. Researchers now say those transfusions can be crucial for many more young sickle cell patients, even those who are showing no outward signs of brain injury.

Alexis Haynes, 12, has come a long way. At age 6, a sudden stroke put her in a coma for a full month."The doctors told us that she wouldn't be able to walk, she wouldn't be able to talk, she wouldn't remember us," Kelvin Haynes, Alexis' father told ABC30.

Every six weeks, Alexis spends hours getting her blood transfused. New red blood cells replace her sickle-shaped ones. While Alexis' stroke was apparent, experts say one in three children with sickle cell suffer silent strokes.

"These are injury to parts of the brain that don't control speech, they don't control movement in an arm or a leg, so they typically go unnoticed," Michael Noetzel, M.D., and Pediatric Neurologist at Washington University School of Medicine, St. Louis, told ABC30.These kids have a higher risk of memory problems. Many have trouble at school. They're also at much higher risk for having a major stroke.

Dr. Noetzel studied 196 children age 5 and older, who had brain scans that showed evidence of silent strokes. For three years, 99 received monthly transfusions, the rest did not. Researchers found the transfusions reduced the risk of strokes of any kind by 58 percent."Now that we have an intervention at hand that could be helpful-there's no reason not to think about screening younger children," Dr. Noetzel explained. Identifying kids at risk before any damage is done.

Risks from transfusions include infections, reactions to donated blood and buildup of iron in the bloodstream. Researchers are planning longer-term studies to see whether transfusions, in combination with other sickle cell treatment options -- like stem cell transplantation -- can help prevent kids from losing cognitive function.

Sickle cell patient, 51, advocates screening for intending couples before marriage - See more at:

SICKLE cell anaemia is an inherited disease. If a person is born with it, steps should be taken to reduce complications resulting from. But it can be prevented as well if intending couples should go for genotype screening and counseling in order to know their genotypes before getting married to avoid having a child with sickle cell disease. This would go a long way in curbing the prevalence of sickle cell anaemia in our society.”
   These were the words of Editor Africa Sickle Cell News and World Report, also President, Ikorodu Sickle Cell Club, and former publicity Secretary Sickle Cell Club, Lagos/Sickle Cell Foundation Nigeria Mr. Ayoola Olajide, during Media Chat on Sickle Cell Disorder to mark his 51 birthday Anniversary in Ikorodu, Lagos. 
   Olajide who revealed that he was diagnosed with sickle cell anaemia in 1966, at the age of two disclosed that Africa Sickle Cell News and World Report will make every edition of sickle cell news available online for free starting from January 2015 to strengthen sickle cell awareness in Africa and throughout the world and help reduce its spread.
   He said: “I am the seventh among eight of my siblings; my mother was AS and my father was AS and I was the only one diagnosed with sickle cell disease among the eight siblings. During my school days I started conducting research on sickle cell, read different books to know more about the disease and that is what helped me to live up to this stage of life.
    “Every body should know his or her genotype especially from primary school children to secondary schools; it would go a long way to reduce the spread of sickle cell disorder in Nigeria, Africa and world at large. People who are at high risk of having a child with sickle cell anemia planning to have children should consider genetic counseling. A counselor can explain the risk of likelihood of having a child who has the disease. He or she also can help explain the choices that are available.
- See more at:


Sickle cell in the Medical Literature


Pulm Circ. 2014 Sep;4(3):482-95. doi: 10.1086/677363.
Sickle erythrocytes and platelets augment lung leukotriene synthesis with downregulation of anti-inflammatory proteins: relevance in the pathology of the acute chest syndrome.
Opene M1, Kurantsin-Mills J2, Husain S1, Ibe BO1.
Initiation, progression, and resolution of vaso-occlusive pain episodes in sickle cell disease (SCD) have been recognized as reperfusion injury, which provokes an inflammatory response in the pulmonary circulation. Some 5-lipoxygenase (5-lox) metabolites are potent vasoconstrictors in the pulmonary circulation. We studied stimulation of production of the inflammatory eicosanoids leukotrienes (LTs) and prostaglandin E2 (PGE2) by isolated rat lungs perfused with sickle (HbSS) erythrocytes. Our hypothesis is that HbSS erythrocytes produce more LTs than normal (HbAA) erythrocytes, which can induce vaso-occlusive episodes in SCD patients. Lung perfusates were collected at specific time points and purified by high-pressure liquid chromatography, and LTC4 and PGE2 contents were measured by enzyme-linked immunosorbent assay (ELISA). Rat lung explants were also cultured with purified HbAA and HbSS peptides, and 5-lox, cyclooxygenase 1/2, and platelet-activating factor receptor (PAFR) proteins were measured by Western blotting, while prostacyclin and LTs produced by cultured lung explants were measured by ELISA. Lung weight gain and blood gas data were not different among the groups. HbSS-perfused lungs produced more LTC4 and PGE2 than HbAA-perfused lungs: 10.40 ± 0.62 versus 0.92 ± 0.2 ng/g dry lung weight (mean ± SEM; P = 0.0001) for LTC4. Inclusion of autologous platelets (platelet-rich plasma) elevated LTC4 production to 12.6 ± 0.96 and 7 ± 0.60 ng/g dry lung weight in HbSS and HbAA perfusates, respectively. HbSS lungs also expressed more 5-lox and PAFR. The data suggest that HbSS erythrocytes and activated platelets in patient's pulmonary microcirculation will enhance the synthesis and release of the proinflammatory mediators LTC4 and PGE2, both of which may contribute to onset of the acute chest syndrome in SCD.
Free Article

PMID: 25621162 [PubMed]

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Am J Hematol. 2015 Jan 23. doi: 10.1002/ajh.23959. [Epub ahead of print]
Increased risk of severe vaso-occlusive episodes after initial acute chest syndrome in children with sickle cell anemia less than 4 years old: Sleep and Asthma Cohort.
Vance LD1, Rodeghier M, Cohen RT, Rosen CL, Kirham FJ, Strunk RC, DeBaun MR.
Previous studies have shown that the highest incidence of acute chest syndrome (ACS) in sickle cell disease (SCD) occurs in children less than 4 years old, and a history of ACS at this age is a risk factor for future ACS episodes. However, the interval associated with the highest risk of subsequent ACS or severe pain is not known. Through this mixed retrospective-prospective observational study, the Sleep and Asthma Cohort, we sought to determine the interval after an initial ACS episode during which the majority of children <4 years old are re-hospitalized for ACS or severe pain. The cumulative prevalence of re-hospitalization for ACS or severe pain within 6 months, 1 years, and 2 years was calculated for children with an initial ACS episode <4 years old and compared to children with an initial ACS episode ≥4 years old. A total of 44.8% and 55.2% of participants had an initial ACS episode <4 years and ≥4 years old (Range: 4-17.7 years), respectively. At 1 year following the initial ACS episode, children <4 years old had a significantly higher cumulative prevalence of re-hospitalizations for ACS or pain as compared to children ≥4 years of age, 62.5% and 39.1%, respectively (P = 0.009). After initial ACS episodes, the majority of children <4 years old will be re-hospitalized for ACS or severe pain within one year, suggesting the need for a therapeutic intervention for this high-risk group. This article is protected by copyright. All rights reserved.
Copyright © 2015 Wiley Periodicals, Inc., A Wiley Company.

PMID: 25619382 [PubMed - as supplied by publisher]

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Am J Hematol. 2015 Jan 23. doi: 10.1002/ajh.23956. [Epub ahead of print]
Single-dose intravenous gammaglobulin can stabilize neutrophil Mac-1 activation in sickle cell pain crisis.
Manwani D1, Chen G, Carullo V, Serban S, Olowokure O, Jang J, Huggins M, Cohen HW, Billett H, Atweh GF, Frenette PS, Shi PA.
Intravenous immunoglobulin (IVIG) decreases neutrophil adhesion to endothelium and red blood cell-neutrophil interactions in sickle cell mice undergoing vaso-occlusion. In this Phase I clinical trial of sickle cell anemia (SCA) patients admitted with pain crisis, we evaluated the status of adhesion molecules on neutrophils in control and IVIG-treated subjects pre- and post-infusion up to 800mg/kg, the same dose used in murine studies. Mac-1 function significantly decreased from baseline in the low-dose IVIG (200-400mg/kg) cohorts. IVIG-related adverse events may have occurred in the high-dose (600-800mg/kg) cohorts. There were no significant increases in neutrophil and leukocyte counts, suggesting that IVIG may more selectively inhibit Mac-1 function as opposed to neutrophil adhesion. This study provides the first in-human validation of pre-clinical murine studies that IVIG can decrease Mac-1 function. This article is protected by copyright. All rights reserved.
© 2015 Wiley Periodicals, Inc.

PMID: 25616042 [PubMed - as supplied by publisher]

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Biol Blood Marrow Transplant. 2015 Jan 20. pii: S1083-8791(15)00037-3. doi: 10.1016/j.bbmt.2015.01.010. [Epub ahead of print]
Allogeneic hematopoietic cell transplantation for children with sickle cell disease is beneficial and cost effective: a single center analysis.
Arnold SD1, Jin Z2, Sands S3, Bhatia M3, Kung A3, Satwani P3.
Limited data exists regarding health care utilization (HCU) in patients receiving allogeneic hematopoietic cell transplantation (alloHCT) for sickle cell disease. Financial data from 2002-2011 was analyzed for 26 alloHCT cases and 48 controls (referred but without alloHCT). HCU of alloHCT was determined over three time periods: pre-alloHCT, during alloHCT (day 0 to day +365), and post-alloHCT. The median total cost per patient during the alloHCT year was $413,000 inpatient and $18,000 outpatient. Post-alloHCT HCU decreased when compared to pre-alloHCT and controls. The median cost of post-alloHCT outpatient visits per patient was significantly less when compared to pre-alloHCT (p=0.044). The median cost of post-alloHCT inpatient visits per patient approached significance when compared to that pre-alloHCT (p=0.079). Sixteen post-alloHCT patients, 19 controls, and 14 unaffected siblings were surveyed using Pediatric Quality of Life Inventory (PedsQL™) and EuroQOL (EQ5D™) questionnaires. The mean PedsQL™ and EQ5D™ scores across all 3 patient groups were not statistically significant (p = 0.2638). When adjusted for health-related quality of life (HRQOL), analysis suggests alloHCT has a positive impact on HRQOL over controls. In summary, this pilot data supports our hypothesis that alloHCT in children with SCD reduces HCU in comparison to controls without alloHCT.
Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

PMID: 25615608 [PubMed - as supplied by publisher]

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Br J Haematol. 2015 Jan 22. doi: 10.1111/bjh.13280. [Epub ahead of print]
Therapeutic phlebotomy is safe in children with sickle cell anaemia and can be effective treatment for transfusional iron overload.
Aygun B1, Mortier NA, Kesler K, Lockhart A, Schultz WH, Cohen AR, Alvarez O, Rogers ZR, Kwiatkowski JL, Miller ST, Sylvestre P, Iyer R, Lane PA, Ware RE; the Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) Trial Investigators.
Serial phlebotomy was performed on sixty children with sickle cell anaemia, stroke and transfusional iron overload randomized to hydroxycarbamide in the Stroke With Transfusions Changing to Hydroxyurea trial. There were 927 phlebotomy procedures with only 33 adverse events, all of which were grade 2. Among 23 children completing 30 months of study treatment, the net iron balance was favourable (-8·7 mg Fe/kg) with significant decrease in ferritin, although liver iron concentration remained unchanged. Therapeutic phlebotomy was safe and well-tolerated, with net iron removal in most children who completed 30 months of protocol-directed treatment.
© 2015 John Wiley & Sons Ltd.

PMID: 25612463 [PubMed - as supplied by publisher]

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Proc Natl Acad Sci U S A. 2015 Jan 20. pii: 201424111. [Epub ahead of print]
Kinetics of sickle cell biorheology and implications for painful vasoocclusive crisis.
Du E1, Diez-Silva M1, Kato GJ2, Dao M3, Suresh S4.
We developed a microfluidics-based model to quantify cell-level processes modulating the pathophysiology of sickle cell disease (SCD). This in vitro model enabled quantitative investigations of the kinetics of cell sickling, unsickling, and cell rheology. We created short-term and long-term hypoxic conditions to simulate normal and retarded transit scenarios in microvasculature. Using blood samples from 25 SCD patients with sickle hemoglobin (HbS) levels varying from 64 to 90.1%, we investigated how cell biophysical alterations during blood flow correlated with hematological parameters, HbS level, and hydroxyurea (HU) therapy. From these measurements, we identified two severe cases of SCD that were also independently validated as severe from a genotype-based disease severity classification. These results point to the potential of this method as a diagnostic indicator of disease severity. In addition, we investigated the role of cell density in the kinetics of cell sickling. We observed an effect of HU therapy mainly in relatively dense cell populations, and that the sickled fraction increased with cell density. These results lend support to the possibility that the microfluidic platform developed here offers a unique and quantitative approach to assess the kinetic, rheological, and hematological factors involved in vasoocclusive events associated with SCD and to develop alternative diagnostic tools for disease severity to supplement other methods. Such insights may also lead to a better understanding of the pathogenic basis and mechanism of drug response in SCD.
Free Article

PMID: 25605910 [PubMed - as supplied by publisher]

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Haematologica. 2015 Jan 16. pii: haematol.2014.114587. [Epub ahead of print]
Elevated hypercoagulability markers in hemoglobin SC disease.
Colella MP1, de Paula EV1, Machado-Neto JA1, Conran N1, Annicchino-Bizzacchi JM1, Costa FF1, Olalla Saad ST1, Traina F2.
Hemoglobin SC disease is a very prevalent hemoglobinopathy, however very little is known specifically about this condition. There appears to be an increased risk of thromboembolic events in hemoglobin SC disease, but studies evaluating the hemostatic alterations are lacking. We describe a cross-sectional observational study evaluating coagulation activation markers in adult hemoglobin SC patients, in comparison with sickle cell anemia patients and healthy controls. A total of 56 hemoglobin SC and 39 sickle cell anemia patients were included in the study, all in steady state, and 27 healthy controls. None of the patients were in use of hydroxyurea. Hemoglobin SC patients presented a significantly up-regulated relative expression of tissue factor, as well as elevations in thrombin-antithrombin complex and D-dimer, in comparison to controls (p<0.01). Hemoglobin SC patients presented lower tissue factor expression, and thrombin-antithrombin complex and D-dimer levels when compared to sickle cell anemia patients (p<0.05). Endothelial activation (soluble thrombomodulin and soluble vascular cell adhesion molecule-1), and inflammation (tumor necrosis factor-alpha) markers were both significantly elevated in hemoglobin SC patients when compared to controls, being as high as the levels seen in sickle cell anemia. Overall, in hemoglobin SC patients, higher hemolytic activity and inflammation were associated with a more intense activation of coagulation, and hemostatic activation was associated with two very prevalent chronic complications seen in hemoglobin SC disease: retinopathy and osteonecrosis. In summary, our results demonstrate that hemoglobin SC patients present a hypercoagulable state, although this manifestation was not as intense as that seen in sickle cell anemia.
Copyright © 2015, Ferrata Storti Foundation.
Free Article

PMID: 25596272 [PubMed - as supplied by publisher]

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J Pediatr Hematol Oncol. 2015 Jan 8. [Epub ahead of print]
A Comparison of Pain Assessment Measures in Pediatric Sickle Cell Disease: Visual Analog Scale Versus Numeric Rating Scale.
Myrvik MP1, Drendel AL, Brandow AM, Yan K, Hoffmann RG, Panepinto JA.
Given the availability of various pain severity scales, greater understanding of the agreement between pain scales is warranted. We compared Visual Analog Scale (VAS) and Numeric Rating Scale (NRS) pain severity ratings in children with sickle cell disease (SCD) to identify the relationship and agreement between pain scale ratings. Twenty-eight patients (mean±SD age, 14.65±3.12 y, 50% female) receiving pain interventions within the emergency department completed serial VAS and NRS pain severity ratings every 30 minutes. Data were used to calculate the relationship (Spearman correlation) and agreement (Bland-Altman approach) between the VAS and NRS. One hundred twenty-eight paired VAS-NRS measurements were obtained. VAS and NRS ratings were significantly correlated for the initial assessment (rs=0.88, P<0.001) and all assessments (rs=0.87, P<0.001). Differences between VAS and NRS means were -0.52 (P=0.006) for the initial assessment and -0.86 (P<0.001) across all assessments. The difference between VAS and NRS ratings decreased as pain severity increased across all assessments (P=0.027), but not the initial assessment. Within pediatric patients with SCD, VAS and NRS ratings were found to trend together; however, VAS scores were found to be significantly lower than NRS scores across assessments. The agreement between the 2 measures improved at increasing levels of pain severity. These findings demonstrate that the VAS and NRS are similar, but cannot be used interchangeably when assessing self-reported pain in SCD.

PMID: 25575295 [PubMed - as supplied by publisher]

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Hematol Rep. 2014 Dec 3;6(4):5502. doi: 10.4081/hr.2014.5502. eCollection 2014.
Exertional sickling: questions and controversy.
Blinder MA1, Russel S2.
Sickle cell trait (SCT) occurs in about 8% of African-Americans and is often described to be of little clinical consequence. Over time, a number of risks have emerged, and among these are rare but catastrophic episodes of sudden death in athletes and other individuals associated with physical activities which is often described as exercise collapse associated with sickle trait (ECAST). Despite an epidemiologic link between SCT and sudden death as well as numerous case reports in both medical literature and lay press, no clear understanding of the key pathophysiologic events has been identified. Strategies for identification of individuals at risk and prevention of ECAST have been both elusive and controversial. Stakeholders have advocated for different approaches to this issue particularly with regard to screening for hemoglobin S. Furthermore, the recommendations and guidelines that are in place for the early recognition of ECAST and the prevention and treatment of the illness are not well defined and remain fragmented. Among the cases identified, those in collegiate football players in the United States are often highlighted. This manuscript examines these case studies and the current recommendations to identify areas of consensus and controversy regarding recommendations for prevention, recognition and treatment of ECAST.
PMCID: PMC4274478 Free PMC Article

PMID: 25568759 [PubMed]

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Transfusion. 2015 Jan 9. doi: 10.1111/trf.12987. [Epub ahead of print]
Changing practice: red blood cell typing by molecular methods for patients with sickle cell disease.
Casas J1, Friedman DF, Jackson T, Vege S, Westhoff CM, Chou ST.
Extended red blood cell (RBC) antigen matching is recommended to limit alloimmunization in patients with sickle cell disease (SCD). DNA-based testing to predict blood group phenotypes has enhanced availability of antigen-negative donor units and improved typing of transfused patients, but replacement of routine serologic typing for non-ABO antigens with molecular typing for patients has not been reported.
This study compared the historical RBC antigen phenotypes obtained by hemagglutination methods with genotype predictions in 494 patients with SCD. For discrepant results, repeat serologic testing was performed and/or investigated by gene sequencing for silent or variant alleles.
Seventy-one typing discrepancies were identified among 6360 antigen comparisons (1.1%). New specimens for repeat serologic testing were obtained for 66 discrepancies and retyping agreed with the genotype in 64 cases. One repeat Jk(b-) serologic phenotype, predicted Jk(b+) by genotype, was found by direct sequencing of JK to be a silenced allele, and one N typing discrepancy remains under investigation. Fifteen false-negative serologic results were associated with alleles encoding weak antigens or single-dose Fyb expression.
DNA-based RBC typing provided improved accuracy and expanded information on RBC antigens compared to hemagglutination methods, leading to its implementation as the primary method for extended RBC typing for patients with SCD at our institution.
© 2015 AABB.

PMID: 25573464 [PubMed - as supplied by publisher]

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Clin J Pain. 2015 Jan 6. [Epub ahead of print]
Development, Content Validity and User Review of a Web-Based Multi-Dimensional Pain Diary for Adolescent and Young Adults with Sickle Cell Disease.
Bakshi N1, Stinson J, Ross D, Lukombo I, Mittal N, Joshi SV, Belfer I, Krishnamurti L.
Vaso-occlusive pain, the hallmark of sickle cell disease (SCD), is a major contributor to morbidity, poor health-related quality of life and healthcare utilization associated with this disease. There is wide variation in the burden, frequency and severity of pain experienced by patients with SCD. As compared to healthcare utilization for pain, a daily pain diary captures the breadth of the pain experience and is a superior measure of pain burden and its impact on patients. Electronic pain diaries based on real time data capture methods overcome methodological barriers and limitations of paper pain diaries but their psychometric properties have not been formally established in patients with SCD.
To develop and establish the content validity of a web-based multi-dimensional pain diary for adolescents and young adults with SCD and conduct an end-user review to refine the prototype.
Following identification of items, a conceptual model was developed. Interviews with adolescents and young adults with SCD were conducted. Subsequently, end-user review with use of the electronic pain diary prototype was conducted.
Two iterative cycles of in-depth cognitive interviews in adolescents and young adults with SCD informed the design and guided the addition, removal and modification of items in the multi-dimensional pain diary. Potential end-users provided positive feedback on the design and prototype of the electronic diary.
A multi-dimensional web-based electronic pain diary for adolescents and young adults with SCD has been developed and content validity and initial end-user reviews have been completed.

PMID: 25565585 [PubMed - as supplied by publisher]

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Mol Med. 2014 Dec 16;20 Suppl 1:S37-42. doi: 10.2119/molmed.2014.00187.
Advances in sickle cell therapies in the hydroxyurea era.
Field JJ1, Nathan DG2.
In the hydroxyurea era, insights into mechanisms downstream of erythrocyte sickling have led to new therapeutic approaches for patients with sickle cell disease (SCD). Therapies have been developed that target vascular adhesion, inflammation and hemolysis, including innovative biologics directed against P-selectin and invariant natural killer T cells. Advances in hematopoietic stem cell transplant and gene therapy may also provide more opportunities for cures in the near future. Several clinical studies are underway to determine the safety and efficacy of these new treatments. Novel approaches to treat SCD are desperately needed, since current therapies are limited and rates of morbidity and mortality remain high.
Free Article

PMID: 25549232 [PubMed - in process]

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Platelets. 2014 Dec 30:1-4. [Epub ahead of print]
A novel inflammatory role for platelets in sickle cell disease.
Davila J1, Manwani D, Vasovic L, Avanzi M, Uehlinger J, Ireland K, Mitchell WB.
Abstract The severe pain, ischemia and organ damage that characterizes sickle cell disease (SCD) is caused by vaso-occlusion, which is the blockage of blood vessels by heterotypic aggregates of sickled erythrocytes and other cells. Vaso-occlusion is also a vasculopathy involving endothelial cell dysfunction, leukocyte activation, platelet activation and chronic inflammation resulting in the multiple adhesive interactions between cellular elements. Since platelets mediate inflammation as well as thrombosis via release of pro- and anti-inflammatory molecules, we hypothesized that platelets may play an active inflammatory role in SCD by secreting increased amounts of cytokines. Since platelets have been shown to contain mRNA and actively produce proteins, we also hypothesized that SCD platelets may contain increased cytokine mRNA. In this cross-sectional study, we sought to compare both the quantity of cytokines secreted and the cytokine mRNA content, between SCD and control platelets. We measured the secretion of Th1, Th2, and Th17-related cytokines from platelets in a cohort of SCD patients. We simultaneously measured platelet mRNA levels of those cytokines. Platelets from SCD patients secreted increased quantities of IL-1β, sCD40L, and IL-6 compared to controls. Secretion was increased in patients with alloantibodies. Additionally, mRNA of those cytokines was increased in SCD platelets. Platelets from sickle cell patients secrete increased amounts of inflammatory cytokines, and contain increased cytokine mRNA. These findings suggest a novel immunological role for platelets in SCD vasculopathy, in addition to their thrombotic role, and strengthen the rationale for the use of anti-platelet therapy in SCD.

PMID: 25548984 [PubMed - as supplied by publisher]

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Social Theory & Health (2015) 13, 62–77. doi:10.1057/sth.2014.17

Actor network theory, agency and racism: The case of sickle cell trait and US athletics Bob Cartera and Simon M Dysonb

  1. aUniversity of Leicester, Attenborough 502, Leicester LE1 7RH, UK
  2. bDe Montfort University, Hawthorn Building 1.27, Leicester LE1 9BH, UK. E-mail:


Actor Network Theory (ANT) has invigorated recent social theory. In assessing the agency of things ANT offers a fresh perspective on materiality and on the role of the non-human (animate and inanimate), and has challenged the central place of sociology in social research. One increasingly influential concept associated with ANT is that of ‘assemblage’. The article takes a contemporary concern – the sudden death of student athletes later found to be genetic carriers of sickle cell – and uses this to assess the concept. Although ANT, and the notion of assemblage, offer interesting avenues for research, the difficulty in sustaining a plausible notion of durable, structured social interests carries political consequences.
Sickle Cell Conferences and Events

FSCDR Hollywood, FL
9th Annual Sickle Cell Disease Research and Educational Symposium and 38th National Sickle Cell Disease Scientific Meeting (April 10-13, 2015)

 Sickle Cell in Focus (SCiF), London, UK
Date:  Monday 15 – Tuesday 16 June 2015
Venue: The Light @ Euston, Friends House, 173-177 Euston Road, London, NW1 2BJ, UK

The 9th Sickle Cell in Focus returns to London in 2015. Professor Swee Lay Thein and Dr John Tisdale have once again planned an excellent programme. This year, in addition to updating on the emerging and current clinical and management issues realted to sickle cell disease, there will be a focus on new drug developments, clinical trials and new genetics. 

Sickle Cell in Focus has become a internationally renowned educational update for sickle cell disease.  It attracts a wide audience of clinicians, academics and other healthcare professionals involved in the disease from around the world.


Sickle Cell News for 2014

New tool helps young adults with sickle cell disease in the transition to adult care Child and adolescent hematologists at Boston Medical Center (BMC) have developed a tool to gauge how ready young adults with sickle cell disease are for a transition into adult care. In a new article for the Journal of Pediatric Hematology/Oncology, Amy Sobota, MD, MPH, and her collaborators have shown that a questionnaire geared to the needs of young adults with sickle cell disease can pinpoint areas of need before the patient goes into an adult clinic.

BMC's sickle cell disease transition clinic, which is unique in Boston, was established in 2008 and serves approximately 45 patients. Sickle cell disease is a hemoglobin disorder, the molecule in red blood cells that carries oxygen to the tissues. Due to a genetic mutation, sickle cell patients make red blood cells that are shaped like a crescent or "sickle." These patients are often anemic and can get bouts of extreme pain when sickled red blood cells become caught in small vessels of the body. Sickle cell disease traditionally has had a high mortality rate; however, children with sickle cell disease are now living longer, healthier lives thanks to early diagnosis and effective treatment.

These welcome changes have given new importance to the young patient's point of transition into adult care. Previous studies have shown that patients with SCD who are transitioning from pediatric to adult care have more admissions and emergency department visits. "We saw that these patients had specific needs, and that is why we started the transition clinic at BMC," said Sobota, who is an attending in pediatric hematology/oncology at BMC and an assistant professor of pediatrics at Boston University School of Medicine.

To determine the tool's efficacy, the researchers looked at the answers provided by 33 patients between the ages of 18 and 22 who completed the assessment. A majority, 97 percent, of the respondents said they could explain sickle cell disease to another person and that they understood "how they got" the genetic disease, and 94 percent understood that sickle cell disease might be passed on to their children.

All of the patients said that they planned to attend college or obtain post-high-school training, but only 70 percent knew where to find information about job training and opportunities. Sixty four percent of transitioning patients said they understood the various types of health insurance available to them, but only 13 percent had drawn up a portable medical history form that they could give to adult healthcare providers. Encouragingly, 97 percent of young sickle cell patients claimed a good social support system.

Finally, patients were asked about their ability to manage independent living and 73 percent of the patients had some job experience, full- or part-time. Although all of the patients were 18 and over, only 79 percent said they were already going to doctor's appointments on their own. However, few mentioned that they had anxiety about transitioning to adult care.

"Our study indicates that this assessment tool – the only one of its kind – provides important information to physicians of patients with sickle cell disease who are transitioning from pediatric to adult care," said Sobota. "Caregivers can use this information from patients in order to effectively tailor and guide their treatment and education through this transition."

Sickle cell disease: The forgotten survivors see the story at
Funding Opportunity Announcement for the Sickle Cell Disease Treatment Demonstration Program has been released.  You can find the and the FOA number is HRSA-14-078.  You can also find more information about the FOA at
There will be a informational webinar regarding this funding opportunity on Monday, May 12 at 3:00pm Eastern Standard Time.

Please share this information as widely as possible.  If you have any questions regarding the FOA, please submit your question to me by email, so that I may address the question for the entire pool of potential applicants.  Please do not call me to ask questions regarding the FOA, as I will just ask you to submit your question by email.

Thank you,
Edward Donnell Ivy, MD, MPH
Medical Officer, Genetics Services Branch
Division of Services for Children with Special Health Needs
Maternal and Child Health Bureau
5600 Fishers Lane. Rm 18-A-19
Rockville, MD 20857
Sickle cell in the Medical Literature

  1. Blood. 2014 Apr 24. [Epub ahead of print]

    How I treat renal complications in sickle cell disease.
    Sharpe CC1, Thein SL.

    Author information:

    1. Department of Renal Medicine, King's College London, London, United Kingdom;


    Renal disease is one of the most frequent and severe complications experienced by patients with sickle cell disease; its prevalence is likely to increase as the patient population ages. We recommend regular monitoring for early signs of renal involvement and a low threshold for the use of hydroxyurea as preventative measures for end stage renal disease. Once renal complications are detected, a careful assessment of the patient is required to rule out other causes of renal disease. Proteinuria and hypertension should be managed aggressively and the patient referred to a specialist nephrology center when progressive decline in renal function noted. For the few patients who develop advanced chronic kidney disease, timely planning for dialysis and transplantation can significantly improve outcome and we recommend an exchange blood transfusion policy for all patients on the transplant waiting list and for those with a functioning graft. Alongside the invasive treatment regimes, it is important to remember that renal failure in conjunction with sickle cell disease does carry a significant burden of morbidity, and that focusing on symptom control has to be central to good patient care.

    PMID: 24764565 [PubMed - as supplied by publisher]
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  2. Thromb Res. 2014 May; 133 Suppl 1:S52-3. doi: 10.1016/j.thromres.2014.03.021.

    Red blood cells and thrombin generation in sickle cell disease.

    Whelihan MF1, Lim MY1, Key NS2.

    Author information:

    1. Division of Hematology/Oncology, Department of Medicine, University of NC at Chapel Hill, USA.

    2. Division of Hematology/Oncology, Department of Medicine, University of NC at Chapel Hill, USA. Electronic address:


    The prothrombotic nature of sickle cell disease (SCD) is evidenced by the chronically elevated levels of almost all coagulation activation biomarkers, and an increased incidence of certain thrombotic events, including venous thromboembolism. Numerous studies have attempted to define the extent and elucidate the mechanism of the observed increase in thrombin generation in SCD patients in vivo. In general, these studies were performed using thrombin generation assays in platelet poor or platelet rich plasma and showed little difference in endogenous thrombin potential between the SCD cohort and healthy matched controls. In SCD, erythrocytes and monocytes have been demonstrated to exhibit procoagulant characteristics. Thus, the absence of these cellular components in standard thrombin generation assays may fail to reflect global hypercoagulability in the whole blood of patients with SCD. We were therefore surprised to see no difference in net thrombin generation in tissue factor-initiated initiated clotting of whole blood from patients with SCD. However, we are continuing to reconcile these seemingly disparate observations by slight modifications of the whole blood model that include alternative coagulation triggers and a re-examination of the net thrombin generation when the protein/protein S system is simultaneously interrogated.

    Copyright © 2014 Elsevier Ltd. All rights reserved.

    PMID: 24759144 [PubMed - in process]
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  3. Br J Health Psychol. 2014 Apr 23. doi: 10.1111/bjhp.12099. [Epub ahead of print]

    Assessing the quality of life of children with sickle cell anaemia using self-, parent-proxy, and health care professional-proxy reports.

    Constantinou C1, Payne N, Inusa B.

    Author information:

    1Psychology Department, Middlesex University, London, UK.



    The quality of life (QoL) of children with sickle cell anaemia (SCA) in the United Kingdom has not been examined, and a discrepancy measure based on Gap theory has rarely been used. This study investigated whether (1) child self-reports of QoL using a discrepancy measure (the Generic Children's QoL Measure; GCQ) are lower than those from healthy children, (2) proxy reports from parents and health care professionals are lower than child self-reports, and (3) demographic and disease severity indicators are related to QoL.


    An interdependent groups, cross-sectional design was implemented. Seventy-four children with SCA, their parent, and members of their health care team completed the GCQ. Demographic and disease severity indicators were recorded. GCQ data from healthy children were obtained from the UK Data Archive.


    Contrary to past research, when examining generic discrepancy QoL, children with SCA did not report a lower QoL than healthy children, and parent- and health care professional-proxy reports were not lower than child self-reports. Few of the demographic and disease severity indicators were related to QoL.


    Proxy reports may be used to gain a more complete picture of QoL, but should not be a substitute for self-reports. The explanation for the relatively high levels of QoL reported is not clear, but children with SCA may have realistic expectations about their ideal-self, place greater emphasis on aspects other than health in shaping their QoL, and define achievements within the limits of their illness. Future research should focus on psychological factors in explaining QoL. Statement of contribution What is already known on this subject? Children with sickle cell disease (SCD) generally have a reduced QoL compared with healthy children, but there appears to be no research measuring QoL in paediatric SCD in the United Kingdom. Proxy QoL reports from parents are often lower than child self-reports, but there is less research examining proxy reports from health care professionals. Previous research has measured paediatric QoL using measures of current health-related QoL, but this is not in line with the WHO's definition of QoL as the discrepancy between current state and expectations. What does this study add? Children with Sickle cell anaemia do not have an impaired discrepancy QoL; they may have realistic expectations about their ideal-self and define achievements within the limits of their illness. Health care professionals are able to gauge a SCA child's discrepancy QoL better than parents. The GCQ (a generic discrepancy measure of QoL) takes into account expectations about ideal QoL and does not emphasize health; it may be of use to Psychologists working with SCA children.

    © 2014 The British Psychological Society.

    PMID: 24758574 [PubMed - as supplied by publisher]
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  4. Br J Haematol. 2014 Apr 18. doi: 10.1111/bjh.12879. [Epub ahead of print]

    Management of the acute painful crisis in sickle cell disease- a re-evaluation of the use of opioids in adult patients.

    Telfer P1, Bahal N, Lo A, Challands J.

    Author information:

    1. Department of Haematology, Royal London Hospital, Barts Health NHS Trust, London, UK.


    Management of the acute painful crisis (APC) of sickle cell disease (SCD) remains unsatisfactory despite advances in the understanding and management of acute pain in other clinical settings. One reason for this is an unsophisticated approach to the use of opioid analgesics for pain management. This applies to haematologists who are responsible for developing acute sickle pain management protocols for their patients, and to health care staff in the acute care setting. The objective of this article is to evaluate the evidence for use of opioids in APC management. We have highlighted the possibilities for improving management by using alternatives to morphine, and intranasal (IN) or transmucosal routes of administration for rapid onset of analgesia in the emergency department (ED). We suggest how experience gained in managing acute sickle pain in children could be extrapolated to adolescents and young adults. We have also questioned whether patients given strong opioids in the acute setting are being safely monitored and what resources are required to ensure efficacy, safety and patient satisfaction. We also identify aspects of care where there are significant differences of opinion, which require further study by randomized controlled trial.

    © 2014 John Wiley & Sons Ltd.

    PMID: 24750050 [PubMed - as supplied by publisher]
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  5. Lancet Glob Health. 2014 Feb; 2(2):e80-e89.

    Global migration and the changing distribution of sickle haemoglobin: a quantitative study of temporal trends between 1960 and 2000.

    Piel FB1, Tatem AJ2, Huang Z3, Gupta S4, Williams TN5, Weatherall DJ6.

    Author information:

    1. Evolutionary Ecology of Infectious Disease Group, Tinbergen Building, Department of Zoology, University of Oxford, Oxford, UK ; Global Sickle Cell Disease Network, Toronto, ON, Canada.

    2. Department of Geography and Environment, University of Southampton, Southampton, UK ; Fogarty International Center, National Institutes of Health, Bethesda, MD, USA.

    3. Center for Infectious Disease Dynamics and Department of Biology, Pennsylvania State University, PA, USA.

    4. Evolutionary Ecology of Infectious Disease Group, Tinbergen Building, Department of Zoology, University of Oxford, Oxford, UK.

    5. Global Sickle Cell Disease Network, Toronto, ON, Canada ; Kenya Medical Research Institute-Wellcome Trust Programme, Centre for Geographic Medicine Research-Coast, Kilifi District Hospital, Kilifi, Kenya ; Department of Medicine, Imperial College, St Mary's Hospital, London, UK.

    6. Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK.



    Changes in the geographical distribution of genetic disorders are often thought to happen slowly, especially when compared with infectious diseases. Whereas mutations, genetic drift, and natural selection take place over many generations, epidemics can spread through large populations within a few days or weeks. Nevertheless, population movements can interfere with these processes, and few studies have been done of their effect on genetic disorders. We aimed to investigate the effect of global migration on the distribution of the sickle-cell gene-the most common and clinically significant haemoglobin structural variant.


    For each country, we extracted data from the World Bank's Global Bilateral Migration Database about international human migrations between 1960 and 2000. We combined this information with evidence-based estimates of national HbS allele frequencies, generated within a Bayesian geostatistical framework, to analyse temporal changes in the net numbers of migrants, and classified countries with an index summarising these temporal trends.


    The number of international migrants increased from 92•6 million in 1960, to 165•2 million in 2000. The estimated global number of migrants with HbS increased from about 1•6 million in 1960, to 3•6 million in 2000. This increase was largely due to an increase in the number of migrants from countries with HbS allele frequencies higher than 10%, from 3•1 million in 1960, to 14•2 million in 2000. Additionally, the mean number of countries of origin for each destination country increased from 70 (SE 46) in 1960, to 98 (48) in 2000, showing an increasing diversity in the network of international migrations between countries. Our index of change map shows a patchy distribution of the magnitude of temporal changes, with the highest positive and negative values scattered across all continents.


    Global human population movements have had a substantial effect on the distribution of the HbS gene. Population movements can create a long-term burden on health-care systems. Our findings, which emphasise countries in which migration fluxes are changing the most, should increase awareness about the global burden of haemoglobinopathies and encourage policy makers to implement specific public health interventions, such as screening programmes and genetic counselling.

    Wellcome Trust, European Research Council, Bill & Melinda Gates Foundation, National Institute of Allergy and Infectious Diseases-National Institutes of Health, the Research and Policy for Infectious Disease Dynamics program, Fogarty International Center.

    PMCID: PMC3986033 Free PMC Article

    PMID: 24748392 [PubMed]
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  6. J Pain Symptom Manage. 2014 Apr 14. pii: S0885-3924(14)00182-1. doi: 10.1016/j.jpainsymman.2014.02.002. [Epub ahead of print]

    Perceived Discrimination in Health Care is Associated with a Greater Burden of Pain in Sickle Cell Disease.

    Haywood C Jr1, Diener-West M2, Strouse J3, Carroll CP3, Bediako S4, Lanzkron S3, Haythornthwaite J3, Onojobi G5, Beach MC3;IMPORT Investigators.

    Author information:

    1. The Johns Hopkins School of Medicine. Electronic address:

    2. The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.

    3. The Johns Hopkins School of Medicine.

    4. The University of Maryland, Baltimore County, Baltimore, Maryland.

    5. The Howard University Hospital, Washington, DC, USA.



    Perceived discriminatory experiences in society have been associated with a higher burden of pain among some minority patient populations.


    To describe the extent to which patients with sickle cell disease (SCD) perceive discrimination from health care providers, and to examine the association of these experiences with the burden of chronic SCD pain.


    Cross-sectional analysis of data collected at baseline of a prospective cohort study of SCD patient experiences of care (n = 291). Perceived race-based and disease-based discrimination from health care providers were measured using subscales adapted from the Interpersonal Processes of Care Survey. Discrimination scores were examined for their association with patient characteristics and measures of pain burden using descriptive, bivariate, and multivariate analytic techniques.


    Respondents reported a greater burden of race-based discrimination from health care providers than has been previously reported by African Americans, and they reported a greater amount of disease-based versus race-based discrimination. While age and having difficulty persuading providers about pain were the only patient characteristics independently associated with race-based discrimination, older age, greater emergency room utilization, having difficulty persuading providers about pain, daily chronic pain, fewer "good days" during a week, and a higher severity of pain on their "good days" were independently associated with greater disease-based discrimination.


    Perceived disease-based, but not race-based, discrimination was found to be associated with a greater range of self-reported pain among patients with SCD. If causal, this finding could signal an important new approach to mitigating the burden of pain experienced by persons with SCD.

    Copyright © 2014 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

    PMID: 24742787 [PubMed - as supplied by publisher]
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  7. Pediatr Blood Cancer. 2014 Apr 17. doi: 10.1002/pbc.25059. [Epub ahead of print]

    Outcomes of matched sibling donor hematopoietic stem cell transplantation for severe sickle cell disease with myeloablative conditioning and intermediate-dose of rabbit anti-thymocyte globulin.

    Soni S1, Gross TG, Rangarajan H, Baker KS, Sturm M, Rhodes M.

    Author information:

    1. Division of Hematology/Oncology/BMT, Nationwide Children's Hospital and Department of Pediatrics, The Ohio State University, Columbus, Ohio.



    Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative therapy for sickle cell disease (SCD) in children. Despite excellent outcomes of matched sibling donor (MSD) HSCT, there is still 5-10% chance of rejection and transplant related mortality (TRM) with 12-23% incidence of graft versus host disease (GVHD). We postulated that an intermediate dose of rabbit anti-thymocyte globulin (r-ATG, 10 mg/kg cumulative) would be effective in preventing both rejection and GVHD.


    Fifteen patients, median age 5 (range 1.5-18) years, underwent MSD HSCT using busulfan (≥12.8 mg/kg with first dose pharmacokinetics), cyclophosphamide (total 200 mg/kg) and r-ATG. Bone marrow was the stem cell source; tacrolimus and methotrexate were given for GVHD prophylaxis.


    All patients achieved donor engraftment and there was no TRM. One patient rejected donor cells at 2 months post-transplant. Majority of the patients had high and sustained level of donor chimerism. None of the patients developed ≥Grade II GVHD. Incidence of CMV (10%) and EBV (9%) reactivations was low with rapid immune-reconstitution. Overall survival was 100% with event free survival of 93%.


    Eliminating the risks of TRM and GVHD by optimizing the regimen may lead to further acceptance of HSCT for SCD. Pediatr Blood Cancer © 2014 Wiley Periodicals, Inc.

    © 2014 Wiley Periodicals, Inc.

    PMID: 24740582 [PubMed - as supplied by publisher]
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  8. PLoS One. 2014 Apr 16; 9(4):e94387. doi: 10.1371/journal.pone.0094387. eCollection 2014.
    Outcomes of acute chest syndrome in adult patients with sickle cell disease: predictors of mortality.

    Allareddy V1, Roy A2, Lee MK3, Nalliah RP4, Rampa S5, Allareddy V6, Rotta AT7.

    Author information:

    1. Assistant Professor of Pediatrics, Pediatric Critical Care, Rainbow Babies and Children's Hospital, Cleveland, Ohio, United States of America.

    2. Fellow, Pediatric Critical Care Medicine, Rainbow Babies and Children's Hospital, Cleveland, Ohio, United States of America.

    3. Developmental Biology, Harvard School of Dental Medicine, Boston, Massachusetts, United States of America.

    4. Instructor, Dental Medicine, Harvard University, Boston, Massachusetts, United States of America.

    5. Advanced Graduate Student, Texas A & M University, College station, Texas, United States of America.

    6. Associate Professor, Department of Orthodontics, University of Iowa; Iowa, United States of America.

    7. Professor of Pediatrics, Pediatric Critical Care, Rainbow Babies and Children's Hospital, Cleveland, Ohio, United States of America.


    Adults with sickle cell disease (SCD) are a growing population. Recent national estimates of outcomes in acute chest syndrome (ACS) among adults with SCD are lacking. We describe the incidence, outcomes and predictors of mortality in ACS in adults. We hypothesize that any need for mechanical ventilation is an independent predictor of mortality.


    We performed a retrospective analysis of the Nationwide Inpatient Sample(2004-2010),the largest all payer inpatient database in United States, to estimate the incidence and outcomes of ACS needing mechanical ventilation(MV) and exchange transfusion(ET) in patients >21 years. The effects of MV and ET on outcomes including length of stay (LOS) and in-hospital mortality (IHM) were examined using multivariable linear and logistic regression models respectively. The effects of age, sex, race, type of sickle cell crisis, race, co-morbid burden, insurance status, type of admission, and hospital characteristics were adjusted in the regression models.

    Of the 24,699 hospitalizations, 4.6% needed MV (2.7% for <96 hours, 1.9% for ≥96 hours), 6% had ET, with a mean length of stay (LOS) of 7.8 days and an in-hospital mortality rate (IHM) of 1.6%. There was a gradual yearly increase in ACS hospitalizations that needed MV (2.6% in 2004 to 5.8% in 2010). Hb-SS disease was the phenotype in 84.3% of all hospitalizations. After adjusting for a multitude of patient and hospital related factors, patients who had MV for <96 hours (OR = 67.53,p<0.01) or those who had MV for ≥96 hours(OR = 8.73,p<0.01) were associated with a significantly higher odds for IHM when compared to their counterparts. Patients who had MV for ≥96 hours and those who had ET had a significantly longer LOS in-hospitals(p<0.001).


    In this large cohort of hospitalized adults with SCD patients with ACS, the need for mechanical ventilation predicted higher mortality rates and increased hospital resource utilization. Identification of risk factors may enable optimization of outcomes.

    PMCID: PMC3989222 Free PMC Article

    PMID: 24740290 [PubMed - in process]
    Related citations

  9. Eur J Haematol. 2014 Apr 15. doi: 10.1111/ejh.12340. [Epub ahead of print]

    Thinking beyond sickling to better understand pain in sickle cell disease.

    Darbari DS1, Ballas S, Clauw DJ.

    Author information:

    1. Division of Hematology, Center for Cancer and Blood Disorders, Children's National Medical Center, Department of Pediatrics, George Washington University, Washington, DC.


    Painful vaso-occlusive crises (VOCs) are the hallmark of sickle cell disease (SCD) however many patients experience frequent daily pain that does not follow the pattern of typical VOCs. This pain of variable severity also referred as persistent pain in the SCD literature, contributes to significant morbidity and poor quality of life and often fails to respond adequately to standard SCD therapies. In this article we briefly describe types of pain encountered in SCD with a special emphasis on persistent pain. We discuss altered pain processing as a potential contributing mechanism which may lead to development and maintenance of persistent pain. We describe advances in the non-SCD pain field that may help improve the understanding of SCD pain. We highlight the need for further investigation in this area since some of these patients with persistent pain may benefit from receiving adjuvant mechanism based therapies used successfully in other non-SCD chronic pain conditions. This article is protected by copyright. All rights reserved.

    This article is protected by copyright. All rights reserved.

    PMID: 24735098 [PubMed - as supplied by publisher]
    Related citations

  10. Mol Med Rep. 2014 Jun; 9(6):2479-84. doi: 10.3892/mmr.2014.2130. Epub 2014 Apr 9.

    Rapid screening for sickle cell disease by polymerase chain reaction-high resolution melting analysis.

    Yue L1, Lin M1, Chen JT2, Zhan XF1, Zhong DS3, Monte-Nguba SM4, Liu PF3, Pan XF3, Huang JH3, Wang X3, Salas Ehapo JC4,Eyi UM4, Yang HT5, Yang LY1.

    Author information:

    1. Medical College of Shantou University, Shantou, Guangdong 515041, P.R. China.

    2. Laboratory Medical Center, Huizhou Central People's Hospital, Huizhou, Guangdong 516001, P.R. China.

    3. The Twenty-Fifth Bath of Chinese Medical Aid Team to the Republic of Equatorial Guinea, Guangzhou, Guangdong 511000, P.R. China.

    4. Hospital Regional De Malabo, Malabo 999115, The Republic of Equatorial Guinea.

    5. Laboratory Medical Center, Chaozhou Central Hospital, Chaozhou, Guangdong 521021, P.R. China.


    Each year, ~300,000 individuals with sickle cell disease (SCD), a hemoglobinopathy caused by β globin gene mutation, are born, and >75% of those are in Africa. The present study examined 511 individuals on the island of Bioko (Equatorial Guinea) and attempted to establish a method for rapid sickle cell disease screening. Following DNA extraction and polymerase chain reaction (PCR) amplification, high resolution melting (HRM) analysis was used to assess the specificity of fluorescence signals of the PCR products and to differentiate various genotypes of these products. The analytical results of HRM were validated using DNA sequencing. By HRM analysis, 80 out of 511 samples were classified as hemoglobin S (Hb S) heterozygotes, while 431 out of 511 samples were classified as wild type. No mutant homozygote was identified. DNA sequencing indicated that within the 431 wild type samples as indicated by HRM analysis, one case was actually a Hb S heterozygote and another case was a rare hemoglobin S C genotype (sickle hemoglobin C disease). One out of 80 suspected Hb S heterozygotes as indicated by HRM was confirmed as wild-type by DNA sequencing and the results of residual 508 cases were consistent for HRM analysis and sequencing. In conclusion, HRM analysis is a simple, high efficiency approach for Hb S screening and is useful for early diagnosis of SCD and particularly suitable for application in the African area.

    PMID: 24718623 [PubMed - in process]
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Sickle Cell Conferences and Events

Global Sickle Cell Diseases Network Conference: Rio De Janeiro, Brazil, 2014 website  the planned April 9-11 meeting of GSCDN and WISSH in Rio de Janeiro has been postponed to November 11-14, 2014. The postponement is to enable the GSCDN and WISSH meetings to be held in conjunction with the 2nd Global Congress on Sickle Cell Disease.  Also, there was concern that the April date would be in partial conflict with the 8th  Annual SCD Research and Education Symposium and National Sickle Cell Disease Scientific Meeting in Florida, US on April 11-14, which will for the first time have a major international component. See  for information as it becomes available.

Event: Sickle Cell in Focus (SCiF) Date: Monday 15 – Tuesday 16 September 2014

Venue: National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, Washington, USA
This year we have been invited by the National Heart, Lung and Blood Institute (NHLBI) to hold SCiF the National Institutes of Health campus in Bethesda, Maryland USA. This is a fantastic opportunity to visit such a prestigious institution and our plan is to alternate the location yearly between King’s College London and NHLBI.

SCiF is now in its 8th year the event has become a world-class educational update for sickle cell disease. Over two intensive days we will focus on the treatment and management of sickle cell disease and provide a comprehensive update on recent research news.  It attracts a wide audience of clinicians, academics and other healthcare professionals involved in the disease from around the world. 

To book: Online booking will be open soon.  If you would like to be kept up-to-date, please join the STSTN mailing list by sending an email to:

Contact details: / + 44 (0) 20 7848 5441 /

September 19-20 2014, Duke-UNCConference 2nd Annual Engaging Providers and Families to Improve Care for Individuals with Sickle Cell Conference. Save the dates. More information to follow.

Sickle Cell Partners of the Carolinas Presents “Sickle Cell Disease…. Let’s Talk About It” Date: Saturday, October 25, 2014 Time: 8am to 3pm Place: Charlotte, North Carolina Web:

Sickle Cell News for May 2013

June 19 World Sickle Cell Day

The World Health Organization (WHO) has started work to promote a worldwide agenda to address hemoglobin dysfunctions.

WHO has made a commitment to:

  • Recognize that sickle cell disease is a major health issue.
  • Increase awareness of the world community regarding sickle cell disease.
  • Eliminate harmful and wrong prejudices associated with sickle cell disease.
  • Urges member countries where sickle cell disease is a public health problem to establish health programs at the national level and operate specialized centers for sickle cell disease and facilitate access to treatment.
  • Promote satisfactory access to medical services to people affected with sickle cell disease.
  • Provide technical support to all countries to prevent and manage sickle cell disease.
  • Promote and help research to improve the lives of people affected with sickle cell disease.

The World Sickle Cell day is celebrated across the globe with special emphasis in African Nations and Asia. The celebrations include a press, media campaigns, music shows, cultural activities, and talk shows.

The main emphasis is hence on educating medical professionals, care givers, and associated personnel about prevention, research, and resources to minimize the complications due to sickle cell disease. Hence June 19th is devoted mainly to spread awareness, through talks, seminars, pamphlets, literature and consultations.

New Video  

New Parents hand book and Children’s DVD produced in the UK

The 3rd Edition of, 'A Parents guide to managing Sickle Cell Disease', in English is available on the UK national screening web site and on the Brent Centre web site It is being translated into French also and will be available in the summer. A new children's DVD, 'My Sickle Cell Disease and Me', funded by Roald Dhal, aimed at children aged 5 - 11years is available on the Brent Centre web site


Fellow colleagues, you are invited to participate in the“Public Health Webinar Series on Hemoglobinopathies” Hosted by: The Division of Blood Disorders, CDC

4th Thursday of every month from 2:00PM – 3:00PM EST

6/27: Beta-globin Haplotype Analysis in Children with Sickle Cell Anemia

Dr. Christopher Bean, National Center on Birth Defects and Developmental Disabilities, CDC  

7/25: Nurses’ Impact on the Stigmatization of Individuals with Sickle Cell: Challenges and Recommendations

Dr. Coretta Jenerette, International Association of Sickle Cell Nurses and Physician Assistants

8/22: Mental Health and Learning Needs in children with Sickle Cell Disease

Dr. Patricia Kavanagh, Boston University School of Medicine/Boston Medical Center  

9/26: NHLBI Sickle Cell Disease Guidelines

Dr. Joylene John-Sowah, National Heart Lung and Blood Institute, NIH  

10/24: Current Data on Efficacy and Effectiveness of Hydroxyurea in Children with Sickle Cell Disease

Dr. Winfred Wang, St. Jude Children’s Research Hospital

November/December: --- No Webinars--- 

If you have ideas on topics for future webinars, or have any questions or comments about this series please submit them to Shae Pope

The purpose of this webinar series is to offer a hemoglobinopathies learning collaborative platform for providers, consumers, educators, and scientists.

CDC Web based Sickle Cell Resources

CDC’s YouTube Link:

CDC Video Archive (

CDC Sickle Cell Disease Webpage:

Articles in the Medical Literature for May

J Pain. 2013 May 20. pii: S1526-5900(13)00938-3. doi: 10.1016/j.jpain.2013.03.007. [Epub ahead of print]

Validation of the Sickle Cell Disease Pain Burden Interview-Youth. <>

Zempsky WT
O'Hara EA
Santanelli JP
Palermo TM
New T
Smith-Whitley K
Casella JF

Division of Pain and Palliative Medicine, Department of Pediatrics, Connecticut Children's Medical Center, Hartford, Connecticut; University of Connecticut School of Medicine, Farmington, Connecticut. Electronic address:


The purpose of this study was to develop and validate a brief, clinically relevant, multidimensional interview to assess pain burden among children and adolescents with sickle cell disease (SCD). The Sickle Cell Disease Pain Burden Interview-Youth (SCPBI-Y) was developed using a panel of experts, patients, and caregivers. Validation was undertaken with children and youth with SCD, ages 7 to 21 years (N = 129), recruited from 4 urban children's hospitals. Participants were recruited from inpatient (n = 62) and outpatient (n = 67) settings. The SCPBI-Y demonstrated strong internal consistency reliability, cross-informant concordance (child-caregiver), and test-retest reliability (outpatient setting). Moderate construct validity was found with validated measures of functional ability, pain, and quality of life. The SCPBI-Y demonstrated construct validity using a contrasted group approach between youth in inpatient versus outpatient settings and by severity of SCD symptoms, suggesting that youth in inpatient settings and with higher disease severity exhibited greater pain burden. Discriminant validity was found between SCPBI-Y and mood. Our preliminary findings suggest that the SCPBI-Y is a valid and reliable multidimensional interview that can be used in different clinical settings to evaluate pain burden among children and adolescents with SCD. PERSPECTIVE: Multifaceted pain assessments are salient in providing optimal care to children and adolescents with SCD; however, current evaluations are lengthy and cumbersome to administer clinically. The current study introduces and validates a brief, clinically useful multidimensional interview to evaluate pain burden specific to youth with SCD.

Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

PMID: 23701707 [PubMed - as supplied by publisher]

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PLoS Pathog. 2013 May; 9(5):e1003327. doi: 10.1371/journal.ppat.1003327. Epub 2013 May 16.

Hemoglobinopathies: Slicing the Gordian Knot of Plasmodium falciparum Malaria Pathogenesis.

Taylor SM
Cerami C
Fairhurst RM

Division of Infectious Diseases and International Health, Duke University Medical Center, Durham, North Carolina, United States of America ; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States of America.


Plasmodium falciparum malaria kills over 500,000 children every year and has been a scourge of humans for millennia. Owing to the co-evolution of humans and P. falciparum parasites, the human genome is imprinted with polymorphisms that not only confer innate resistance to falciparum malaria, but also cause hemoglobinopathies. These genetic traits-including hemoglobin S (HbS), hemoglobin C (HbC), and α-thalassemia-are the most common monogenic human disorders and can confer remarkable degrees of protection from severe, life-threatening falciparum malaria in African children: the risk is reduced 70% by homozygous HbC and 90% by heterozygous HbS (sickle-cell trait). Importantly, this protection is principally present for severe disease and largely absent for P. falciparum infection, suggesting that these hemoglobinopathies specifically neutralize the parasite's in vivo mechanisms of pathogenesis. These hemoglobin variants thus represent a "natural experiment" to identify the cellular and molecular mechanisms by which P. falciparum produces clinical morbidity, which remain partially obscured due to the complexity of interactions between this parasite and its human host. Multiple lines of evidence support a restriction of parasite growth by various hemoglobinopathies, and recent data suggest this phenomenon may result from host microRNA interference with parasite metabolism. Multiple hemoglobinopathies mitigate the pathogenic potential of parasites by interfering with the export of P. falciparum erythrocyte membrane protein 1 (PfEMP1) to the surface of the host red blood cell. Few studies have investigated their effects upon the activation of the innate and adaptive immune systems, although recent murine studies suggest a role for heme oxygenase-1 in protection. Ultimately, the identification of mechanisms of protection and pathogenesis can inform future therapeutics and preventive measures. Hemoglobinopathies slice the "Gordian knot" of host and parasite interactions to confer malaria protection, and offer a translational model to identify the most critical mechanisms of P. falciparum pathogenesis.

PMCID: PMC3656091 Free PMC Article

PMID: 23696730 [PubMed - in process]

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Icon for Public Library of Science Icon for PubMed Central

Value Health. 2013 May; 16(3):A121. doi: 10.1016/j.jval.2013.03.579. Epub 2013 May 3.
Expanding concepts of opioid-taking behavior in sickle cell disease: A multi-phase, mixed methods study.

Alsalman AJ
Li Wong JK
Hassan NT
Smith WR

Virginia Commonwealth University, Richmond, VA, USA.

PMID: 23693291 [PubMed - in process]

Related citations

Pediatr Blood Cancer. 2013 May 15. doi: 10.1002/pbc.24588. [Epub ahead of print]

Association Between Baseline Fetal Hemoglobin Levels and Incidence of Severe Vaso-Occlusive Pain Episodes in Children With Sickle Cell Anemia.

Bhatnagar P
Keefer JR
Casella JF
Barron-Casella EA
Bean CJ
Hooper CW
Payne AB
Arking DE
Debaun MR

McKusick-Nathans Institute of Genetic Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland.


The ameliorating effect of high fetal hemoglobin (HbF) levels on the incidence of pain episodes in sickle cell anemia (SCA) is well-known; however, in children this relationship is less clearly established. We hypothesized that higher HbF levels in children with SCA are associated with fewer severe pain episodes. A meta-analysis of data from the Silent Infarct Transfusion Trial (n = 456) and the Cooperative Study of Sickle Cell Disease (n = 764), demonstrated that baseline HbF levels were associated with the incidence of severe pain, commonly defined across studies as an event requiring hospitalization (P-value = 0.02). Pediatr Blood Cancer © 2013 Wiley Periodicals, Inc.

Copyright © 2013 Wiley Periodicals, Inc.

PMID: 23677903 [PubMed - as supplied by publisher]

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J Pediatr Hematol Oncol. 2013 May 9. [Epub ahead of print]

Transcranial Doppler in Sickle Cell Disease.

Sarkar N
Sharma VK

*Division of Neurology, National University Hospital †Yong Loo Lin School of Medicine National University of Singapore, Singapore.

PMID: 23669727 [PubMed - as supplied by publisher]

Related citations 

Clin J Pain. 2013 May 9. [Epub ahead of print]

Differences in Pain Management Between Hematologists and Hospitalists Caring for Patients With Sickle Cell Disease Hospitalized for Vasoocclusive Crisis.

Shah N
Rollins M
Landi D
Shah R
Bae J
De Castro LM

*Department of Pediatric Hematology/Oncology †Division of Hematology ‡Department of Pediatrics §Division of Oncology ∥Department of Hospital Medicine, Duke University Medical Center, Durham, NC.


OBJECTIVES:: Sickle cell disease (SCD) is a chronic disease characterized by multiple vaso-occlusive complications and is increasingly cared for by hospitalists. The purpose of this study is to examine differences in pain management between hematologists and hospitalists. METHODS: We performed a single-institution, retrospective review of pain management patterns and outcomes in adult SCD patients hospitalized for vaso-occlusive crisis. RESULTS:: Over 26 months, we found a total of 298 patients (120 cared for by the hematologists and 178 by hospitalists), with a mean age of 32 (range 19-58). Patients cared for by hospitalists had a lower total number of hours on a patient controlled analgesia (PCA) device (171 vs. 212 hours, P=0.11). Hospitalists also were significantly more likely to utilize demand only PCA (42% vs. 23%, P=0.002) and had a significantly lower rate of using both continuous and demand PCA (54% vs. 67%, P=0.04). In addition, patients cared for by hospitalists had a significantly shorter hospitalization (8.4 days) compared to hematologists (10 days, P=0.04) with a non-significant difference in 7 and 30 day readmission rates (7.2% vs. 6.7% and 40% vs. 35% respectively). CONCLUSION:: We found patients cared for by hospitalists more frequently utilized home oral pain medication during admission, had shorter lengths of hospitalization, and did not have a significant increase in readmission rates.

PMID: 23669451 [PubMed - as supplied by publisher]

Related citations 

Clin Pediatr (Phila). 2013 May 9. [Epub ahead of print]

Incidence of Serious Bacterial Infections in Febrile Children With Sickle Cell Disease.

Bansil NH
Kim TY
Tieu L
Barcega B

1Loma Linda University, Loma Linda, CA, USA.


Objective. To determine the incidence of serious bacterial infections in febrile children with sickle cell disease and to describe the outcomes of children discharged from the pediatric emergency department. Methods. We conducted a retrospective chart review of 188 febrile patients with sickle cell disease presenting to our pediatric emergency department over a 10-year period. Serious bacterial infection was defined as bacteremia, meningitis, urinary tract infection, osteomyelitis, or pneumonia. Results. Our overall incidence rate for serious bacterial infections was 16.0% (95% confidence interval [CI] = 10.8% to 21.2%). Pneumonia had the highest incidence rate of 13.8% (95% CI = 8.8% to 18.8%). This was followed by bacteremia and urinary tract infections, both with incidence rates of 1.1% (95% CI = 0.0% to 2.5%). We had no cases of meningitis or osteomyelitis in our study group. Conclusion. We had an incidence of 16.0% for serious bacterial infections in febrile children with sickle cell disease, with the majority of patients diagnosed with pneumonia.

PMID: 23661790 [PubMed - as supplied by publisher]

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Haematologica. 2013 May 3. [Epub ahead of print]

A randomized, placebo-control trial of arginine therapy for the treatment of children with sickle cell disease hospitalized with vaso-occlusive pain episodes.

Morris CR
Kuypers FA
Lavrisha L
Ansari M
Sweeters N
Stewart M
Gildengorin G
Neumayr L
Vichinsky EP



Vaso-occlusive painful episodes are the leading cause of hospitalizations and emergency department visits in sickle cell disease, and are associated with increased mortality. Low nitric oxide bioavailability contributes to vasculopathy in sickle cell disease. Since arginine is the obligate substrate for nitric oxide production, and an acute deficiency is associated with pain, we hypothesized that arginine may be a beneficial treatment for pain related to sickle cell disease. Thirty-eight children with sickle cell disease hospitalized for 56 episodes of pain were randomized into this double-blinded placebo-controlled trial. Patients received L-arginine (100mg/kg TID) or placebo for 5 days or until discharge. A significant reduction in total parenteral opioid use by 54% (1.9+/-2.0mg/kg vs. 4.1+/-4.1mg/kg, p=0.02) and lower pain scores at discharge (1.9+/-2.4 vs. 3.9+/-2.9, p=0.01) were observed in the treatment arm compared to placebo. There was no significant difference in hospital length of stay (4.1+/-01.8 vs. 4.8+/-2.5 days, p=0.34), although a trend favored the arginine arm, and total opioid use correlated strongly to length of admission (r=0.86, p<0.0001). No drug-related adverse events were observed. Arginine therapy represents a novel intervention for vaso-occlusive painful episodes. A reduction of narcotic use by >50% is remarkable. Arginine is a safe and inexpensive intervention with narcotic-sparing effects that may be a beneficial adjunct to standard therapy for sickle cell-related pain in children. A large multi-center trial is warranted in order to confirm these observations. ( identifier: NCT01796678).

Free Article

PMID: 23645695 [PubMed - as supplied by publisher]

Related citations <

J Pediatr Hematol Oncol. 2013 May; 35(4):289-298.

Barriers to Hematopoietic Cell Transplantation Clinical Trial Participation of African American and Black Youth With Sickle Cell Disease and Their Parents. <>

Omondi NA
Ferguson SE
Majhail NS
Denzen EM
Buchanan GR
Haight AE
Labotka RJ
Rizzo JD
Murphy EA

*National Marrow Donor Program †Center for International Blood and Marrow Transplant Research and University of Minnesota, Minneapolis, MN ‡The University of Texas Southwestern Medical Center, Children's Medical Center, Dallas, TX §Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA ∥Chicago Sickle Cell Center, University of Illinois, Chicago, IL ¶Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin Clinical Cancer Center, Milwaukee, WI.


African Americans and Blacks have low participation rates in clinical trials and reduced access to aggressive medical therapies. Hematopoietic cell transplantation (HCT) is a high-risk but potentially curative therapy for sickle cell disease (SCD), a disorder predominantly seen in African Americans. We conducted focus groups to better understand participation barriers to HCT clinical trials for SCD. Nine focus groups of youth with SCD (n=10) and parents (n=41) were conducted at 3 sites representing the Midwest, South Atlantic, and West South Central US. Main barriers to clinical trial participation included gaps in knowledge about SCD, limited access to SCD/HCT trial information, and mistrust of medical professionals. For education about SCD/HCT trials, participants highly preferred one-on-one interactions with medical professionals and electronic media as a supplement. Providers can engage with sickle cell camps to provide information on SCD/HCT clinical trials to youth and local health fairs for parents/families. Youth reported learning about SCD through computer games; investigators may find this medium useful for clinical trial/HCT education. African Americans affected by SCD face unique barriers to clinical trial participation and have unmet HCT clinical studies education needs. Greater recognition of these barriers will allow targeted interventions in this community to increase their access to HCT.

PMCID: PMC3659415 [Available on 2014/5/1]

PMID: 23612380 [PubMed - as supplied by publisher]

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Am J Med. 2013 May; 126(5):443-9. doi: 10.1016/j.amjmed.2012.12.016.

Venous thromboembolism in adults with sickle cell disease: a serious and under-recognized complication.

Naik RP
Streiff MB
Haywood C Jr
Nelson JA
Lanzkron S .

Department of Medicine, Division of Hematology, Johns Hopkins University, Baltimore, MD 21205, USA.



Sickle cell disease is recognized as a hypercoagulable state; however, the frequency and characteristics of venous thromboembolism in sickle cell patients have not been well defined. The purpose of this study was to establish the prevalence and risk factors for venous thromboembolism in a large cohort of patients with sickle cell disease and determine the relationship between venous thromboembolism and mortality.


We performed a cross-sectional study of 404 sickle cell disease patients cared for at the Sickle Cell Center for Adults at Johns Hopkins. Demographic, sickle cell disease-specific comorbidity, and venous thromboembolism data were collected on all patients.


One hundred one patients (25%) had a history of venous thromboembolism with a median age at diagnosis of 29.9 years. A history of non-catheter-related venous thromboembolism was found in 18.8% of patients. Sickle variant genotypes conferred a higher risk of non-catheter-related venous thromboembolism compared with sickle cell anemia genotypes (SS/Sβ(0)) (relative risk [RR] 1.77; 95% confidence interval [CI], 1.18-2.66). Tricuspid regurgitant jet velocity ≥2.5 m/s also was associated with non-catheter-related venous thromboembolism (RR 1.65; 95% CI, 1.12-2.45). Thirty patients (7.4%) died during the study period. Adjusting for all variables, non-catheter-related venous thromboembolism was independently correlated with death (RR 3.63; 95% CI, 1.66-7.92).


Venous thromboembolism is common in adults with sickle cell disease. Sickle variant genotypes and tricuspid regurgitant jet velocity ≥2.5 m/s are associated with non-catheter-related venous thromboembolism. In addition, non-catheter-related venous thromboembolism appears to be an independent risk factor for death in our cohort. These results suggest that disease-specific prophylaxis and treatment strategies for venous thromboembolism should be investigated in sickle cell disease patients.

Copyright © 2013 Elsevier Inc. All rights reserved.

PMCID: PMC3627211 [Available on 2014/5/1]

PMID: 23582935 [PubMed - in process]

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Pediatr Blood Cancer. 2013 May; 60(5):828-35. doi: 10.1002/pbc.24459. Epub 2013 Jan 17.

Age-related treatment patterns in sickle cell disease patients and the associated sickle cell complications and healthcare costs.

Blinder MA
Vekeman F
Sasane M
Trahey A
Paley C
Duh MS

Department of Medicine, Washington University in St. Louis, St. Louis, Missouri, USA.



This study explored the blood transfusion patterns, SCD complications, utilization of iron chelation therapies (ICT), healthcare resource use, and costs in pediatric, transitioning (18 years old) and adult patients with SCD.


Data from Florida (1998-2009), New Jersey (1996-2009), Missouri (1997-2010), Kansas (2001-2009), and Iowa (1998-2010) state Medicaid were used. Patients with ≥2 SCD diagnoses and ≥1 transfusion event were included. Rates of transfusion events, SCD complications, and proportion of eligible patients receiving ICT were calculated. ICT eligibility was defined as receiving ≥10 transfusions over lifetime. SCD complications included pain, pulmonary event, infection event, renal, cardiovascular, stroke, leg ulcers, and avascular necrosis. Regressions were used to assess risk factors for transfusion and identify the main drivers of costs.


The sample included 3,208 patients. The transfusion rate increased from 1-year-old to a peak at 16 years old, then dropped until age 26 and remained stable thereafter. In contrast the frequency of diagnoses for SCD complications increased markedly after age 16. Post-transition patients (≥18 years old) were significantly associated with fewer transfusions (odds ratio: 0.80, P = 0.002). Among eligible patients for ICT, there was no statistically significant difference in total cost between the ICT and no ICT groups (adjusted cost difference, $136, P = 0.114).


Patients transitioning to adult care received less transfusions and hydroxyurea, less ICT when eligible for chelation therapy, had higher healthcare costs and suffered from more frequent SCD related complications than pediatric patients. These findings highlight the changes in treatment patterns corresponding to transition to adult care.

Copyright © 2013 Wiley Periodicals, Inc.

PMID: 23335275 [PubMed - indexed for MEDLINE]

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Pediatr Blood Cancer. 2013 May; 60(5):823-7. doi: 10.1002/pbc.24392. Epub 2012 Nov 14.

National trends in incidence rates of hospitalization for stroke in children with sickle cell disease.

McCavit TL
Xuan L
Zhang S
Flores G
Quinn CT

Division of Pediatric Hematology-Oncology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9063, USA.



The success of primary stroke prevention for children with sickle cell disease (SCD) throughout the United States is unknown. Therefore, we aimed to generate national incidence rates of hospitalization for stroke in children with sickle cell disease (SCD) before and after publication of the Stroke Prevention Trial in Sickle Cell Anemia (STOP trial) in 1998.


We performed a retrospective trend analysis of the 1993-2009 Nationwide Inpatient Sample and Kids' Inpatient Databases. Hospitalizations for SCD patients 0-18 years old with stroke were identified by ICD-9CM code. The primary outcome, the trend in annual incidence rate of hospitalization for stroke in children with SCD, was analyzed by linear regression. Incidence rates of hospitalization for stroke before and after 1998 were compared by the Wilcoxon rank-sum test.


From 1993 to 2009, 2,024 hospitalizations were identified for stroke. Using the mean annual incidence rate of hospitalization for stroke from 1993 to 1998 as the baseline, the rate decreased from 1993 to 2009 (point estimate = -0.022/100 patient years [95% CI, -0.039, -0.005], P = 0.027). The mean annual incidence rate of hospitalization stroke decreased by 45% from 0.51 per 100 patient years in 1993-1998 to 0.28 per 100 patient years in 1999-2009 (P = 0.008). Total hospital days and charges attributed to stroke also decreased by 45% and 24%, respectively.


After publication of the STOP trial and hydroxyurea licensure in 1998, the incidence of hospitalization for stroke in children with SCD decreased across the United States, suggesting that primary stroke prevention has been effective nationwide, but opportunity for improvement remains.

Copyright © 2012 Wiley Periodicals, Inc.

PMID: 23151905 [PubMed - indexed for MEDLINE]

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Blood. 2013 May 21. [Epub ahead of print]

Outcome of patients with hemoglobinopathies given either cord blood or bone marrow transplantation from an HLA-identical sibling. <>

Locatelli F
Kabbara N
Ruggeri A
Ghavamzadeh A
Roberts I
Bernaudin F
Vermylen C
Dalle JH
Stein J
Wynn R
Cordonnier C
Pinto F
Angelucci E
Socié G
Gluckman E
Walters MC
Rocha V

Pediatric Hematology-Oncology, IRCCS Opsedale Pediatrico Bambino Gesu, University of Pavia, Italy;


We analyzed the outcomes of 485 patients with thalassemia major (TM) or sickle cell disease (SCD) receiving HLA-identical sibling cord blood transplantation (CBT, n=96) or bone marrow transplantation (BMT, n=389). Compared to patients given BMT, CBT recipients were significantly younger (median age 6 versus 8 years, p=0.02), and were treated more recently (median year 2001 versus 1999, p<0.01). A higher proportion of patients with TM belonging to classes II-III of the Pesaro classification received BMT (44%) compared to CBT (39%, p<0.01). In comparison with patients receiving BMT (n=259, TM; n=130, SCD), those given CBT (n=66, TM; n=30, SCD) had slower neutrophil recovery, less acute graft-versus-host disease (GVHD) and none had extensive chronic GVHD. With a median follow-up of 70 months, the 6-year overall survival was 95% and 97% after BMT and CBT, respectively (p=0.92). The 6-year disease-free survival (DFS) was 86% and 80% in TM patients after BMT and CBT, respectively, while DFS in SCD patients was 92% and 90%, respectively. The cell dose infused did not influence outcome of patients given CBT. In multivariate analysis, DFS did not differ between CBT and BMT recipients. Patients with TM or SCD have excellent outcomes after both HLA-identical sibling CBT and BMT.

PMID: 23692854 [PubMed - as supplied by publisher]

Related citations

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Transfusion. 2013 May 21. doi: 10.1111/trf.12250. [Epub ahead of print]

Cost-effectiveness of prospective red blood cell antigen matching to prevent alloimmunization among sickle cell patients.

Kacker S
Ness PM
Savage WJ
Frick KD
Shirey RS
King KE
Tobian AA

Department of Pathology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland; Department of Health Policy and Management, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts.



Sickle cell disease is associated with extensive health care utilization; estimated lifetime costs exceed $460,000 per patient. Approximately 30% of chronically transfused sickle cell patients become alloimmunized to red blood cell antigens, but these patients cannot be identified a priori. Prospective antigen matching can prevent alloimmunization, but is costly and may not benefit most patients.


A Markov-based model was constructed to compare the health and financial implications of four alternative antigen-matching strategies for chronically transfused sickle cell patients. The strategies varied by the group of patients receiving matched blood (all patients prophylactically or only patients with a history of alloimmunization [history-based]), and by the extent of antigen matching (limited to C, E, and K, or extended to 11 antigens). Direct medical costs and alloimmunization events were assessed over 10- and 20-year periods, for a hypothetical cohort of initially transfusion-naive patients and for a dynamic population.


Within a hypothetical cohort of initially transfusion-naive patients, implementing prophylactic limited matching for all chronically transfused patients instead of history-based limited matching is expected to cost an additional $765.56 million over 10 years, but result in 2072 fewer alloimmunization events. Within the same cohort, implementing prospective extensive matching is expected to cost $1.86 billion more than history-based extensive matching, but result in 2424 fewer alloimmunization events. Averting a single alloimmunization event using prospective matching would cost $369,482 to $769,284. Among a dynamic population over 10 years, prospective limited matching is expected to cost $358.34 million more than history-based limited matching.


While prospective matching for all transfused patients would reduce alloimmunization, this strategy requires considerable expenditure.

© 2013 American Association of Blood Banks.

 PMID: 23692415 [PubMed - as supplied by publisher]

Related citations

J Pain Palliat Care Pharmacother. 2013 May 21. [Epub ahead of print]

Oral Ketamine for Sickle Cell Crisis Pain Refractory to Opioids.

Jennings CA
Bobb BT
Noreika DM
Coyne PJ

Cara A. Jennings, MD, is a fellow; Barton T. Bobb, MSN, FNP-BC, ACHPN, is an advanced practice nurse; Danielle M. Noreika, MD, is an assistant clinical professor in the Division of Hematology, Oncology and Palliative Care, Massey Cancer Center, Virginia Commonwealth University , Richmond, Virginia , USA ; Patrick J. Coyne, MSN, APRN, FAAN, is Clinical Director, Pain and Palliative Care, Thomas Palliative Care Services, Massey Cancer Center, Virginia Commonwealth University , Richmond, Virginia , USA .


ABSTRACT There is literature demonstrating that the N-methyl-d-aspartate (NMDA) receptor antagonist ketamine has analgesic properties that can be used as an adjuvant to opiates for pain relief in multiple various conditions and pain states. However, there is a lack of published information on ketamine used in persons with sickle cell disease in acute pain crises. The Virginia Commonwealth University Palliative Care team was consulted on a 38-year-old African American female with sickle cell thalassemia in severe acute pain crisis overlying chronic pain related to her disease. Pain control was unable to be achieved with escalating doses of opiates and other adjuvant medications. The patient responded well to an intravenous test dose of ketamine and was subsequently placed on an oral regimen of ketamine in addition to opiates. In the 24-hour period following ketamine initiation, the patient's pain was able to be controlled on decreased amounts of opiates. She was eventually transitioned to an oral opiate and ketamine regimen, which allowed her to be discharged home with pain levels close to her baseline and the ability to function and perform all activities of daily living.

PMID: 23692261 [PubMed - as supplied by publisher]

Related citations

Chest. 2013 May 16. doi: 10.1378/chest.12-1569. [Epub ahead of print]

Environmental tobacco smoke and airway obstruction in children with sickle cell anemia.

Cohen RT
Strunk RC
Field JJ
Rosen CL
Kirkham FJ
Redline S
Stocks J
Rodeghier MJ
Debaun MR



The contribution of environmental tobacco smoke exposure (ETS) to pulmonary morbidity in children with sickle cell anemia (SCA) is poorly understood. We tested the hypothesis that children with SCA and ETS would have an increased prevalence of obstructive lung disease and respiratory symptoms compared to children with SCA but without ETS.


Parent-report of ETS and respiratory symptom frequency were obtained for 245 children with SCA as part of a multi-center prospective cohort study. 196 children completed pulmonary function testing. Multivariable regression models evaluated the associations between ETS exposures at different time points [prenatal, infant (birth-2 years), preschool (2 years -first grade) and current], and lung function and respiratory symptoms.


Among 245 participants, a high prevalence of prior (44%) and current (29%) ETS was reported. Of the 196 children who completed pulmonary function testing, those with parent-reported infant and current ETS were more likely to have airway obstruction (defined as Forced Expiratory Volume in 1 second /Forced Vital Capacity ratio (FEV1/FVC) below the lower limit normal) compared to unexposed children (22.0% vs. 3.1%, p&lt;0.001). Those with ETS also had a lower FEF25-75/FVC ratio (0.82 vs. 0.97, p=0.001) and were more likely to have evidence of bronchodilator responsiveness(23% vs. 11%, p=0.03). Current and prior ETS and in utero exposure were associated with increased frequency of respiratory symptoms.


ETS exposure is associated with evidence of lower airway obstruction and increased respiratory symptoms in SCA.

PMID: 23681054 [PubMed - as supplied by publisher]

Related citations <> 

17. Hamideh D, Alvarez O.  Sickle Cell Disease Related Mortality in the United States (1999–2009 ). [Epub ahead of print  23 APR 2013 DOI: 10.1002/pbc.24557].


Little is known about the national outcome of children and adults with sickle cell disease (SCD) given contemporary care.


We investigated the number of deaths, standardized crude and age-adjusted mortality rates, and causes of death among individuals with SCD across the United States during 1999–2009 according to death certificates by using a publicly available website ( Data were compared to mortality during 1979–1998.


When compared to 1979–1998, mortality significantly decreased by 61% in infants <1 year of age, by 67% in children aged 1–4 years, and by 22–35% in children aged 5–19 years. After 19 years of age, mortality rates increased from 0.6 in the 15–19 year group to 1.4/100,000 in the 20–24 year group,

corresponding to the transition period from pediatric to adult medical care, and this increase was similar during 1979–1998. Although the age groups with the highest mortality were 35–44 years for males and 45–54 years for females, there was a tendency for longer survival because there were more deaths among those individuals 55–74 years of age compared to previous years. For all individuals, the causes of deaths were cardiac disease (31.6%), respiratory (28.1%), renal (16.4%), infectious (14.4%), neurologic (11.9%), and gastrointestinal and hepatobiliary (9.2%) in nature. Cancer was the cause of death in <1%.


Mortality during childhood has decreased significantly. However, the transition period from pediatric to adult care is critical. Risk-reduction, monitoring, and early treatment intervention of cardiovascular disease in adults is warranted.

Sickle Cell Conferences and Events

The Sickle Cell Association of Ontario World Sickle Cell Day conference June18 – 19 Toronto, Ontario , Canada

Event: Sickle Cell in Focus

Date: Thursday 6th - Saturday 8th June 2013

Venue: King’s College London, Denmark Hill campus, London SE5 9RJ

Description: Sickle Cell in Focus is a hugely successful and intensive 2.5 day annual conference. Now in its 7th year, the heart of the event is to update and discuss the current clinical and management issues of sickle cell disease and thalassaemia. This year the programme will include more debates, delegate presentations on complex case studies and more time to network. The conference attracts international and national speakers and delegates and will be of interest to consultants, medical trainees and other healthcare professionals involved in the care of patients with red blood cell disorders, as well as academics with a research interest in this field


To book: Rates for this fantastic conference are incredibly competitive. To attend the full conference (2.5 days) the cost is £250 for Consultants/Public Sector/Charities. For medical trainees it is only £175! For full details and to book online via the KCL eStore, please visit  Contact details: or / + 44 (0) 20 7848 5441 /  

 ESH Eurocord-Ed Eurocord World Cord Blood Congress IV and Innovative Therapies for Sickle Cell Disease Oct 24 – 27, 2013 Monaco

7th Annual Sickle Cell and Thalassaemia Conference: UK  3-5 October 2013
Improving the quality of life for patients affected with Sickle Cell Disease and Thalassaemia

Now in its seventh year, this annual Sickle Cell Disease and Thalassaemia Conference run by Evelina Children’s Hospital at Guy's and St Thomas' NHS Foundation Trust will take place from 3rd to 5th October 2013.Combining theory and clinical practice and drawing on the latest research in the field, this annual Conference is intended for all those health care professionals involved in the diagnosis, treatment and care of patients with Sickle Disease and Thalassaemia.To book or for further information, please visit the website


Sickle Cell News for 2013

Anti-sickling therapies should be focus for sickle cell science

Pain is an undeniable focal point for patients with sickle cell disease but it's not the best focus for drug development, says one of the dying breed of physicians specializing in the condition.

Rather scientists need to get back to the crux of the disease affecting 1 in 500 black Americans and find better ways to prevent the hallmark sickling that impedes red blood cells' oxygen delivery, damaging blood vessel walls and organs along the way, said Dr. Abdullah Kutlar, Director of the Sickle Cell Center at the Medical College of Georgia at Georgia Regents University.

"We have one drug that reduces sickling and we need more," said Kutlar, the 2013 Roland B. Scott, M.D., Lecturer for the 7th Annual Sickle Cell Disease Research and Educational Symposium and National Sickle Cell Disease Scientific Meeting April 14-17 in Miami.

"Pain is very important to someone who is suffering, but by using pain as an end point, we are missing opportunities and wasting drugs that could be very helpful," he said. "Moving forward, I suggest we develop new combination therapies that have anti-sickling capabilities at their center," said Kutlar, noting such cocktail approaches have worked well for cancer and HIV.

Kutlar completed an extensive historical review of patient and study outcomes in preparation for the lecture honoring the late Howard University physician who made it his mission to improve the lives of children with sickle cell disease. Scott's contributions include prompting the National Sickle Cell Control Act of 1972, which established the first federally-funded comprehensive sickle cell centers, including the one at MCG led by Dr. Titus H.J. Huisman.

No doubt Scott, Huisman and others have made a tremendous difference to patients, whose average life expectancy has gone from the teens to the 50s in the past 30 years, Kutlar said. Much of that progress grew out of focusing on the basics, including developing hydroxyurea, still the only Food and Drug Administration-approved drug that targets sickling.

Approved 15 years ago, hydroxyurea works by increasing expression of fetal hemoglobin, which can't sickle. However, it's still not widely used – about 35 percent of Kutlar's adult patients take it, for example – probably for a combination of reasons that include a side effect of weight gain and unsubstantiated concerns that it increases cancer risk. He and his colleagues need to do a better job communicating the benefits of this drug in addition to finding new ones, Kutlar said. Reduced sickling means less damage to blood vessels and organs, he said, noting that the major cause of death in adults and children is acute chest syndrome, a severe pneumonia resulting from cumulative lung damage. A handful of new anti-sickling drugs are in various stages of development, including a thalidomide- derivative pioneered by MCG researchers that also enhances fetal hemoglobin expression.

Other good endpoints for drug development include downstream effects of sickling, such as the unnatural adhesion of red blood cells to blood vessel walls, Kutlar said. Unfortunately work was recently halted on a drug that reduced adhesion but not pain, Kutlar said.

Pain needs to be the primary endpoint only for pain medications, he noted. The good news is that many new pain medications are available for these patients, whose pain crises can be severe enough to require hospitalization and whose chronic pain can impair daily living. However, that circles back to the complex causes of pain. The pain initially likely results from tissues crying out for more oxygen and later from nerve and organ damage resulting from ongoing impaired oxygen supplies. Pain control can get even more complex and difficult because regular use of opiates, a common analgesic for sickle cell patients, actually increases pain sensitivity, Kutlar said.

In addition to finding better therapies, physicians who treat sickle cell patients need to help cultivate the next generation of caregivers, Kutlar said. He's in the minority in that he opted to take care of patients with sickle cell disease rather than pursue the more common – and generally more professionally lucrative – hematology path: treating cancer. "We don't have enough hematologists, period," said Kutlar. The problem does have a good cause: the reality that more patients are living longer. However, the number of physicians to treat adult patients is dismal. Helping cultivate the next generation is a focus of a study led by Kutlar and Dr. Robert W. Gibson, a GRU occupational therapist and medical anthropologist. They are reaching out to primary care physicians – who also are in short supply in this country – as a permanent medical home for patients as they reach adulthood. Kutlar and Gibson are co-principal investigators on $7 million, five-year grant from the National Center on Minority Health and Health Disparities of the National Institutes of Health supporting this initiative as well as the search for new drugs and more.

MCG physicians follow about 1,500 adults and children with sickle cell disease.

Clinical Research Forum selects sickle cell project among 'Top 10' clinical research achievements of 2012

Pioneering research led by Johns Hopkins scientists on the use of partially matched bone marrow transplants to wipe out sickle cell disease has been selected as one of the Top 10 Clinical Research Achievements of 2012 by the Clinical Research Forum. The success of a preliminary clinical trial of the so-called haploidentical transplants has the potential to bring curative transplants to a majority of sickle cell patients who need them, eliminating painful and debilitating symptoms and the need for a lifetime of pain medications and blood transfusions.

On behalf of the research team, Robert A. Brodsky, M.D., the Johns Hopkins Family Professor of Medicine in Oncology and director of the Division of Hematology at the Johns Hopkins University School of Medicine, will receive the award and an additional honor, the Distinguished Clinical Research Achievement Award, at a ceremony on April 18 during the Clinical Research Forum annual meeting in Washington, D.C.

New Web article Sickle Cell Disease Review

Advances in disease management and new treatment models help patients live longer. 1 contact hour of CEU for nurses:

New Video   - Strategies to Improve Implementation of Hydroxyurea

Dr. Courtney Thornburg, Duke Pediatric Sickle Cell Clinic



Fellow colleagues, you are invited to participate in the“Public Health Webinar Series on Hemoglobinopathies” Hosted by: The Division of Blood Disorders, CDC

4th Thursday of every month from 2:00PM – 3:00PM EST

5/23: Baby on Board: What You Need to Know about Pregnancy in the Hemoglobinopathies

Dr. Sophie Lanzkron, Sickle Cell Center for Adults at Johns Hopkins Hospital 

6/27: Beta-globin Haplotype Analysis in Children with Sickle Cell Anemia

Dr. Christopher Bean, National Center on Birth Defects and Developmental Disabilities, CDC  

7/25: Nurses’ Impact on the Stigmatization of Individuals with Sickle Cell: Challenges and Recommendations

Dr. Coretta Jenerette, International Association of Sickle Cell Nurses and Physician Assistants

  8/22: Mental Health and Learning Needs in children with Sickle Cell Disease

Dr. Patricia Kavanagh, Boston University School of Medicine/Boston Medical Center  

9/26: NHLBI Sickle Cell Disease Guidelines

Dr. Joylene John-Sowah, National Heart Lung and Blood Institute, NIH  

10/24: Current Data on Efficacy and Effectiveness of Hydroxyurea in Children with Sickle Cell Disease

Dr. Winfred Wang, St. Jude Children’s Research Hospital

November/December: --- No Webinars--- 

If you have ideas on topics for future webinars, or have any questions or comments about this series please submit them to Shae Pope .

The purpose of this webinar series is to offer a hemoglobinopathies learning collaborative platform for providers, consumers, educators, and scientists.

CDC Web based Sickle Cell Resources

CDC’s YouTube Link:

 CDC Video Archive (

 CDC Sickle Cell Disease Webpage:

Articles in the Medical Literature for April

1. J Pediatr Hematol Oncol. 2013 Apr 24. [Epub ahead of print]

Cytochrome P450 2D6 Polymorphisms and Predicted Opioid Metabolism in African American Children With Sickle Cell Disease.

Yee MM, Josephson C, Hill CE, Harrington R, Castillejo MI, Ramjit R, Osunkwo I.

*Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta Departments of †Pediatrics, Hematology/Oncology ‡Pathology and Laboratory Medicine, Emory University §Emory University School of Medicine, Atlanta, GA.


The opioid medications codeine and hydrocodone, commonly prescribed in sickle cell disease (SCD), require metabolic conversion by cytochrome P450 2D6 (CYP2D6) to morphine and hydromorphone, respectively, to exert their analgesic effects. The CYP2D6 gene is highly polymorphic, with variant alleles that result in decreased, absent, or ultrarapid enzyme activity. Seventy-five children with SCD were tested for CYP2D6 polymorphisms, and metabolic phenotypes were inferred from the genotypes. The most common variant alleles were CYP2D6*2 (normal activity, 28.7%), CYP2D6*17 (reduced activity, 17.3%), CYP2D6*5 (gene deletion, 8.7%), and CYP2D6*4 (absent function, 8.0%). Normal/extensive metabolizer genotypes were found in 28/75 (37.5%), intermediate metabolism in 33/75 (44.0%), poor metabolism in 4/75 (5.3%), ultrarapid metabolism in 3/75 (4.0%), indeterminate in 6/75 (8.0%). Allele frequencies did not vary significantly among different hemoglobin genotypes. Identification of variant CYP2D6 genotypes may identify individuals with altered metabolism and therefore altered analgesic response to codeine and hydrocodone, thus providing a personalized medicine approach to treatment of pain in SCD. Further pharmacokinetic and pharmacodynamic studies are needed to define the relationship of CYP2D6 and other gene polymorphisms to individual opioid effect in SCD.

                PMID: 23619115 [PubMed - as supplied by publisher]

                Related citations

2. J Pediatr Hematol Oncol. 2013 Apr 24. [Epub ahead of print]

Hyperhemolysis in Sickle Cell Disease.

Aragona E, Kelly MJ.

*Division of Hospitalist Medicine, Children's National Medical Center, The George Washington University School of Medicine and Health Sciences, Washington, DC †Division of Pediatric Hematology Oncology, The Floating Hospital for Children at Tufts Medical Center, Tufts University School of Medicine, Boston, MA.


An 18-year-old female with sickle cell disease presented with thigh pain, dark urine, and hematuria within 72 hours of receiving a blood transfusion. Her clinical picture was consistent with hemolysis. Subsequent laboratory workup, however, demonstrated reticulocytopenia without evidence of an antibody-mediated transfusion reaction. As her hemoglobin continued to decrease, she was treated with IVIG and steroids for presumed hyperhemolysis. Clinicians should have a high index of suspicion for hyperhemolysis in sickle cell patients with evidence of hemolysis after a recent transfusion. Differentiating hyperhemolysis from other hemolytic syndromes is critical; transfusions in a hyperhemolytic episode can accelerate hemolysis causing life-threatening anemia.

                PMID: 23619113 [PubMed - as supplied by publisher]

                Related citations

3. J Pediatr Hematol Oncol. 2013 May;35(4):289-298.

Barriers to Hematopoietic Cell Transplantation Clinical Trial Participation of African American and Black Youth With Sickle Cell Disease and Their Parents.

Omondi NA, Ferguson SE, Majhail NS, Denzen EM, Buchanan GR, Haight AE, Labotka RJ, Rizzo JD, Murphy EA.

*National Marrow Donor Program †Center for International Blood and Marrow Transplant Research and University of Minnesota, Minneapolis, MN ‡The University of Texas Southwestern Medical Center, Children's Medical Center, Dallas, TX §Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA Chicago Sickle Cell Center, University of Illinois, Chicago, IL Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin Clinical Cancer Center, Milwaukee, WI.


African Americans and Blacks have low participation rates in clinical trials and reduced access to aggressive medical therapies. Hematopoietic cell transplantation (HCT) is a high-risk but potentially curative therapy for sickle cell disease (SCD), a disorder predominantly seen in African Americans. We conducted focus groups to better understand participation barriers to HCT clinical trials for SCD. Nine focus groups of youth with SCD (n=10) and parents (n=41) were conducted at 3 sites representing the Midwest, South Atlantic, and West South Central US. Main barriers to clinical trial participation included gaps in knowledge about SCD, limited access to SCD/HCT trial information, and mistrust of medical professionals. For education about SCD/HCT trials, participants highly preferred one-on-one interactions with medical professionals and electronic media as a supplement. Providers can engage with sickle cell camps to provide information on SCD/HCT clinical trials to youth and local health fairs for parents/families. Youth reported learning about SCD through computer games; investigators may find this medium useful for clinical trial/HCT education. African Americans affected by SCD face unique barriers to clinical trial participation and have unmet HCT clinical studies education needs. Greater recognition of these barriers will allow targeted interventions in this community to increase their access to HCT.

                PMID: 23612380 [PubMed - as supplied by publisher]

                Related citations

4. J Pediatr Hematol Oncol. 2013 May;35(4):329-30. doi: 10.1097/MPH.0b013e318290c5f3.

Sickle Cell-related Bone Marrow Complications: The Utility of Diffusion-weighted Magnetic Resonance Imaging.

Pratesi A, Medici A, Bresci R, Micheli A, Barni S, Pratesi C.

Misericordia e Dolce Hospital, Prato, Tuscany, Italy.


In sickle cell disease diffusion-weighted imaging (DWI) are helpful, cost-effective, and promising techniques for differentiating bone marrow involvements. So we suggest to consider a MR diffusion panoramic study (whole-body diffusion MR) when multiple follow-up imaging is required in young patients who are at high risk for chronic radiation damage, so that alternatives to PET study may be taken into consideration.

                PMID: 23612384 [PubMed - in process]

                Related citations

5. Eur Cytokine Netw. 2013 Apr 19. [Epub ahead of print]

Altered levels of pro-inflammatory cytokines in sickle cell disease patients during vaso-occlusive crises and the steady state condition.

Keikhaei B, Mohseni AR, Norouzirad R, Alinejadi M, Ghanbari S, Shiravi F, Solgi G.

Thalassemia & Hemoglobinopathy research center, Ahvaz Joundishapur University of Medical Science, Ahvaz, Iran.


Objective: This study aimed to evaluate serum levels of pro-inflammatory cytokines and TGF-β in sickle cell disease (SCD) patients, and to compare the results during vaso-occlusive crisis (VOC) or steady state (StSt) conditions. Methods: 54 SCD patients (37HbSS and 17Sβ+Thal) were enrolled in the study and evaluated in two groups as follows; group A consisted of 39 VOC patients and group B comprised 15 StSt patients. Nineteen healthy volunteers were included as controls. Circulating levels of IL-1, IL-6, IL-8, IL-17,TNF-α and TGF-β were measured using ELISA. Results: Patients in VOC showed higher mean levels of all cytokines than those found in steady-state patients, but this was only marginally significant for IL-8 levels (P = 0.08). Increased levels of TGF-β and IL-17 were found in StSt patients versus normal controls (P = 0.004 and P<0.0001 respectively). A positive correlation was observed between IL-8 and IL-17 in both groups of patients (P = 0.002 and P = 0.005 respectively). Decreased levels of TNF-α, IL-1β and IL-17 were found in hydroxyurea-treated patients. Additionally, significantly higher levels of IL-6 and IL-8 were observed in hydroxyurea-treated and untreated patients than in controls respectively (P = 0.04 and P = 0.01). Conclusions: Our findings indicate that pro-inflammatory cytokines, especially IL-8 and IL-17, could be used as related markers for assessing disease severity, and consequently therapeutic intervention.

                PMID: 23608554 [PubMed - as supplied by publisher]

                Related citations

6. Am J Hematol. 2013 Apr 20. doi: 10.1002/ajh.23457. [Epub ahead of print]

Genetic modifiers of sickle cell anemia in the BABY HUG cohort: Influence on laboratory and clinical phenotypes.

Sheehan VA, Luo Z, Flanagan JM, Howard TA, Thompson BW, Wang WC, Kutlar A, Ware RE; BABY HUG Investigators.

Hematology Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX.


The recently completed BABY HUG trial investigated the safety and efficacy of hydroxyurea in infants with sickle cell anemia (SCA). To investigate the effects of known genetic modifiers, genomic DNA on 190 randomized subjects was analyzed for alpha thalassemia, beta-globin haplotype, polymorphisms affecting endogenous fetal hemoglobin (HbF) levels (XmnI, BCL11A, and HBS1L-MYB), UGT1A1 promoter polymorphisms, and the common G6PD A- mutation. At study entry, infants with alpha thalassemia trait had significantly lower MCV, total bilirubin, and absolute reticulocyte count. Beta-globin haplotypes associated with milder disease had significantly higher hemoglobin and %HbF. BCL11A and XmnI polymorphisms had significant effects on baseline HbF, while UGT1A1 promoter polymorphisms significantly influenced baseline serum bilirubin. At study exit, subjects randomized to placebo still exhibited laboratory effects of alpha thalassemia and other modifiers, while those assigned hydroxyurea had treatment effects that exceeded most genetic influences. The pain phenotype was influenced by HbF modifiers in both treatment groups. These data document that genetic polymorphisms do modify laboratory and clinical phenotypes even in very young patients with SCA. The hydroxyurea effects are more potent, however, indicating that treatment criteria should not be limited to certain genetic subsets, and supporting the use of hydroxyurea for all young patients with SCA.

Copyright © 2013 Wiley Periodicals, Inc., A Wiley Company.

                PMID: 23606168 [PubMed - as supplied by publisher]

                Related citations

7. Hemoglobin. 2013 Apr 19. [Epub ahead of print]

Leg Ulcers in Sickle Cell Disease: Current Patterns and Practices.

Delaney KM, Axelrod KC, Buscetta A, Hassell KL, Adams-Graves PE, Seamon C, Kato GJ, Minniti CP.

National Heart, Lung, and Blood Institute , Bethesda, Maryland , USA.


Leg ulcers are a debilitating complication of patients with sickle cell disease, and their frequency in North America was reported to be 2.5% by the Cooperative Study of Sickle Cell Disease more than 20 years ago. We sought to determine if the frequency of leg ulcers in sickle cell patients in the United States had declined and to assess which treatments providers use most commonly. We sent an e-mail survey to health professionals belonging to the national Sickle Cell Adult Provider Network. Responses were obtained from 31 of them (26.0%). Most of them (96.0%) reported having some patients with leg ulcers. Providers reported a total of 185 patients with active leg ulcers and 224 in the previous 5 years, for a total of 409 patients. Hb SS (homozygous sickle cell anemia) was the most common genotype of affected individuals, followed by Hb SC (double heterozygote for Hb S [β6(A3)Glu→Val, GAG>GTG; HBB: c.20A>T] and Hb C [β6(A3)Glu→Lys, GAG>AAG; HBB: c.19G>A]). Males showed a 2:1 predominance. Two-thirds of patients were treated with either hydroxyurea (HU) or transfusion therapy and most used compression stockings and topical therapies as directed by wound care services. We conclude that leg ulcers continue to be a debilitating complication of young adults with sickle cell disease, despite improved supportive care and the widespread use of disease modifying agents such HU and transfusion. While some providers offer office-based ulcer care, the majority prefer specialty consultation including podiatry, plastic surgery and dermatology. Despite their frequency, there is no clear consensus among providers as to the best treatment.

                PMID: 23600469 [PubMed - as supplied by publisher]

                Related citations

8. Br J Haematol. 2013 Apr 18. doi: 10.1111/bjh.12336. [Epub ahead of print]

Interplay between coagulation and vascular inflammation in sickle cell disease.

Sparkenbaugh E, Pawlinski R.

Division of Hematology/Oncology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.


Sickle cell disease is the most common inherited haematological disorder that leads to the irreversible damage of multiple organs. Although sickling of red blood cells and vaso-occlusion are central to the pathophysiology of sickle cell disease, the importance of haemolytic anaemia and vasculopathy has been recently recognized. A hypercoagulable state is another prominent feature of sickle cell disease and is mediated by activation of both intrinsic and extrinsic coagulation pathways. Growing evidence demonstrates that coagulation may not only contribute to the thrombotic complications, but also to vascular inflammation associated with this disease. This article summarizes the role of vascular inflammation and coagulation activation, discusses potential mechanisms responsible for activation of coagulation and reviews recent data demonstrating the crosstalk between coagulation and vascular inflammation in sickle cell disease.

© 2013 John Wiley & Sons Ltd.

                PMID: 23593937 [PubMed - as supplied by publisher]

                Related citations

9. Br J Haematol. 2013 Apr 17. doi: 10.1111/bjh.12323. [Epub ahead of print]

The effect of hydroxcarbamide therapy on survival of children with sickle cell disease.

Lopes de Castro Lobo C, Pinto JF, Nascimento EM, Moura PG, Cardoso GP, Hankins JS.

Instituto de Hematologia Arthur Siqueira Cavalcanti (HEMORIO), Rio de Janeiro, RJ, Brazil.


Although evidence is accumulating that hydroxycarbamide decreases mortality among adults with sickle cell disease (SCD), there are no published data regarding the effect of hydroxycarbamide on mortality among children. The Paediatric Hydroxycarbamide Program was established to treat children with SCD aged 3-18 years if they met disease severity criteria. Mortality data and clinical/laboratorial effects of hydroxycarbamide were retrospectively collected for the first 9 years of the Program. Mortality among those who received hydroxycarbamide was compared to that of untreated children. Among 1760 subjects, 267 received hydroxycarbamide at a median dose of 20•8 mg/kg/d (range 10-32) for a median of 2 years (range 0•1-6•5). Survival among hydroxycarbamide-treated children was significantly greater than that among untreated ones (99•5% vs. 94•5%, P = 0•01), due primarily to fewer deaths from acute chest syndrome and infection. Hydroxycarbamide therapy was significantly associated with increases in haemoglobin concentration, fetal haemoglobin, mean corpuscular volume, and reduction in platelet counts, reticulocytes and neutrophils. Toxicity was minimal and predominantly mild reversible neutropenia. Significantly fewer hospitalizations and emergency room visits, and shorter admissions were observed among hydroxycarbamide-treated subjects, when compared to the 12-month period prior to treatment initiation. Hydroxycarbamide therapy reduces disease severity and is probably associated with decreased mortality among children with SCD.

© 2013 John Wiley & Sons Ltd.

                PMID: 23590693 [PubMed - as supplied by publisher]

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10. Hemoglobin. 2013 Apr 17. [Epub ahead of print]

Maternal Complications and The Association with Baseline Variables in Pregnant Women with Sickle Cell Disease.

Al-Farsi SH, Al-Riyami NM, Al-Khabori MK, Al-Hunaini MN.

Department of Obstetrics and Gynaecology, Sultan Qaboos University Hospital , Muscat , Sultanate of Oman.


Sickle cell disease is an inherited hemoglobinopathy with multi system complications. It has been associated with multiple maternal complications. A retrospective review of 68 consecutive pregnant women with sickle cell disease, followed in a tertiary center, was conducted over 5 years, to estimate the incidence of different maternal complications and the impact of baseline characteristics. Sixty-eight patients were analyzed (mean age 30 years). Sixty-two patients had a Hb SS genotype. The initial mean hemoglobin (Hb) level was 9.5 g/dL. Twelve patients delivered by Cesarean section. Sixty-five patients required admission for sickle cell disease/pregnancy-related complications [96.0%; 95% confidence interval (95% CI) 91-100]. Infection was seen in 17 patients (25.0%, 95% CI 14-36). Blood transfusions were given to 61 patients (90.0%, 95% CI 82-97). Eight patients had gestational hypertension (18.0%, 95% CI 4-20), while five patients (7.0%, 95% CI 1-14) had pre term labor. One patient developed eclampsia and one had a uterine rupture. One patient died due to post partum hemorrhage. The multi variable logistic regression model on the impact on the major maternal complications revealed none of the baseline factors to be statistically significant. Sickle cell disease patients have low mortality and pregnancy-related morbidity but high sickle cell disease-related morbidity. Prospective studies are needed to confirm these results.

                PMID: 23590330 [PubMed - as supplied by publisher]

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11. ScientificWorldJournal. 2013 Mar 25;2013:694146. doi: 10.1155/2013/694146. Print 2013.

Biologic complexity in sickle cell disease: implications for developing targeted therapeutics.

Gee BE.

Department of Pediatrics, Cardiovascular Research Institute, Morehouse School of Medicine, 720 Westview Drive SW, Atlanta, GA 30310-1495, USA.


Current therapy for sickle cell disease (SCD) is limited to supportive treatment of complications, red blood cell transfusions, hydroxyurea, and stem cell transplantation. Difficulty in the translation of mechanistically based therapies may be the result of a reductionist approach focused on individual pathways, without having demonstrated their relative contribution to SCD complications. Many pathophysiologic processes in SCD are likely to interact simultaneously to contribute to acute vaso-occlusion or chronic vasculopathy. Applying concepts of systems biology and network medicine, models were developed to show relationships between the primary defect of sickle hemoglobin (Hb S) polymerization and the outcomes of acute pain and chronic vasculopathy. Pathophysiologic processes such as inflammation and oxidative stress are downstream by-products of Hb S polymerization, transduced through secondary pathways of hemolysis and vaso-occlusion. Pain, a common clinical trials endpoint, is also complex and may be influenced by factors outside of sickle cell polymerization and vascular occlusion. Future sickle cell research needs to better address the biologic complexity of both sickle cell disease and pain. The relevance of individual pathways to important sickle cell outcomes needs to be demonstrated in vivo before investing in expensive and labor-intensive clinical trials.

PMCID: PMC3621302 Free PMC Article

                PMID: 23589705 [PubMed - in process]

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12. J Pediatr Hematol Oncol. 2013 Apr 11. [Epub ahead of print]

Predictors for Bacteremia in Febrile Sickle Cell Disease Children in the Post-7-Valent Pneumococcal Conjugate Vaccine Era.

Chang TP, Kriengsoontorkij W, Chan LS, Wang VJ.

*Division of Emergency Medicine and Transport, Children's Hospital Los Angeles ‡Division of Biostatistics and Outcomes Assessment, Los Angeles County+University of Southern California Medical Center §Department of Pediatrics, Division of Research on Children, Youth, and Families, Keck School of Medicine of USC, Los Angeles, CA †Department of Pediatrics, Siriraj Hospital/Mahidol University, Bangkok, Thailand.


OBJECTIVES: The objective of this study was to determine the incidence of bacteremia in febrile sickle cell disease (SCD) children before and after the 7-valent pneumococcal vaccine (PCV7), and to determine clinical factors associated with bacteremia following PCV7. PATIENTS AND METHODS:: We reviewed all febrile events in SCD children from 1993 to 2009 at a tertiary care pediatric center, comparing general bacteremia and pneumococcal bacteremia incidence for 3 time periods around the PCV7. Univariate analysis and stepwise logistic regression identified clinical factors most associated with bacteremia in this population. RESULTS:: Of 466 SCD children identified, there were 2504 febrile events. We found 84 cases of bacteremia; 8 were pneumococcal. The general bacteremia incidence decreased significantly from 5.60% to 2.44% (P<0.001) over time. Pneumococcal bacteremia incidence did not decrease (P=0.13). Following PCV7, we identified 4 significant independent risk factors associated with general bacteremia: the presence of a central venous line, higher absolute band count, toxic appearance, and older age. CONCLUSIONS:: In febrile SCD children, the incidence of general bacteremia decreased over time. No decrease in pneumococcal bacteremia was found. The presence of a central venous line, absolute band count, clinical appearance, and age may help predict bacteremia in this population.

                PMID: 23588338 [PubMed - as supplied by publisher]

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13. Am J Med. 2013 May;126(5):443-9. doi: 10.1016/j.amjmed.2012.12.016.

Venous Thromboembolism in Adults with Sickle Cell Disease: A Serious and Under-recognized Complication.

Naik RP, Streiff MB, Haywood C Jr, Nelson JA, Lanzkron S.

Department of Medicine, Division of Hematology, Johns Hopkins University, Baltimore, Md. Electronic address:



Sickle cell disease is recognized as a hypercoagulable state; however, the frequency and characteristics of venous thromboembolism in sickle cell patients have not been well defined. The purpose of this study was to establish the prevalence and risk factors for venous thromboembolism in a large cohort of patients with sickle cell disease and determine the relationship between venous thromboembolism and mortality.


We performed a cross-sectional study of 404 sickle cell disease patients cared for at the Sickle Cell Center for Adults at Johns Hopkins. Demographic, sickle cell disease-specific comorbidity, and venous thromboembolism data were collected on all patients.


One hundred one patients (25%) had a history of venous thromboembolism with a median age at diagnosis of 29.9 years. A history of non-catheter-related venous thromboembolism was found in 18.8% of patients. Sickle variant genotypes conferred a higher risk of non-catheter-related venous thromboembolism compared with sickle cell anemia genotypes (SS/Sβ(0)) (relative risk [RR] 1.77; 95% confidence interval [CI], 1.18-2.66). Tricuspid regurgitant jet velocity ≥2.5 m/s also was associated with non-catheter-related venous thromboembolism (RR 1.65; 95% CI, 1.12-2.45). Thirty patients (7.4%) died during the study period. Adjusting for all variables, non-catheter-related venous thromboembolism was independently correlated with death (RR 3.63; 95% CI, 1.66-7.92).


Venous thromboembolism is common in adults with sickle cell disease. Sickle variant genotypes and tricuspid regurgitant jet velocity ≥2.5 m/s are associated with non-catheter-related venous thromboembolism. In addition, non-catheter-related venous thromboembolism appears to be an independent risk factor for death in our cohort. These results suggest that disease-specific prophylaxis and treatment strategies for venous thromboembolism should be investigated in sickle cell disease patients.

Copyright © 2013 Elsevier Inc. All rights reserved.

PMCID: PMC3627211 [Available on 2014/5/1]

                PMID: 23582935 [PubMed - in process]

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14. Stem Cells Transl Med. 2013 Apr 11. [Epub ahead of print]

Umbilical Cord Blood: An Evolving Stem Cell Source for Sickle Cell Disease Transplants.

Shenoy S.

Division of Pediatric Hematology/Oncology, Washington University, St. Louis Children's Hospital, St. Louis, Missouri, USA.


Allogeneic hematopoietic stem cell transplantation has proven benefit in controlling sickle cell disease-related vasculopathy and organ damage. Myeloablative matched sibling donor cord transplants have excellent outcomes in sickle cell disease. Unrelated donor transplant options are often deferred because of a lack of suitable human leukocyte antigen-matched donors, a problem especially relevant to minority populations. Umbilical cord blood transplantation allows for more mismatching from the graft-versus-host disease perspective and the donor pool is expandable with effort and education. Drawbacks such as increased rates of graft rejection, a fixed cell dose, delayed immune reconstitution, and transplant-related mortality have deterred unrelated cord transplant efforts. However, the transplant community continues to make enormous strides in this transplant realm in areas of immunogenetics, stem cell expansion, conditioning regimens, and supportive care. This has allowed the development of new studies that are currently ongoing, exploring ways to make cord blood transplantation successful and safer. The goal is to make unrelated donor cord blood transplantation for sickle cell disease merit early consideration in patients who stand to benefit from this approach.

                PMID: 23580541 [PubMed - as supplied by publisher]

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15. Clin Nurs Res. 2013 Apr 8. [Epub ahead of print]

Evaluation of the SCKnowIQ Tool and Reproductive CHOICES Intervention Among Young Adults With Sickle Cell Disease or Sickle Cell Trait.

Gallo AM, Wilkie DJ, Wang E, Labotka RJ, Molokie RE, Stahl C, Hershberger PE, Zhao Z, Suarez ML, Johnson B, Pullum C, Angulo R, Thompson A.

University of Illinois at Chicago, College of Nursing, Department of Women, Children and Family Health Science, Chicago, IL, USA.


The study purpose was to evaluate a computer-based questionnaire (SCKnowIQ) and CHOICES educational intervention using cognitive interviewing with childbearing-aged people with sickle cell disease (SCD) or trait (SCT). Ten control group participants completed the SCKnowIQ twice. Ten intervention group participants completed the SCKnowIQ before and after the CHOICES intervention. Most participants found the questionnaire items appropriate and responded to items as the investigators intended. Participants' responses indicated that the information on SCD and SCT and reproductive options was understandable, balanced, important, and new to some. Internal consistency and test-retest reliability were adequate (.47 to .87) for 4 of the 6 scales, with significant within-group changes in knowledge scores for the intervention group but not for the control group. Findings show evidence for potential efficacy of the intervention, but proof of efficacy requires a larger randomized study.

                PMID: 23572406 [PubMed - as supplied by publisher]

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16. Pediatr Hematol Oncol. 2013 Apr 9. [Epub ahead of print]

Prevalence of Pneumococcal Bacteremia in Children with Sickle Cell Disease.

Patel A, Zuzo A, Imran H, Siddiqui AH.

University of South Alabama College of Medicine , Mobile, Alabama , USA.


We performed a retrospective chart review of children with sickle cell disease hospitalized for fever at our local institution. We reviewed 456 hospitalizations in 133 patients between January 2006 and June 2012. The prevalence of true bacteremia was 4%. The mean C-reactive protein values and temperatures were nonsignificantly higher in patients with positive blood cultures. The mean time to detection was 22.5 hours in bacteremia compared to 32.6 hours in blood cultures that grew contaminants (p = .034). Only two (0.4%) cases of pneumococcal bacteremia were reported and both occurred before May 2010, which marks the introduction of 13-valent pneumococcal vaccine (PCV13). Both patients with pneumococcal bacteremia had discontinued penicillin prophylaxis after the age of 5 years. The first patient was immunized but contracted a nonvaccine serotype (23B). The second patient was partially vaccinated and acquired a vaccine-preventable serotype (23F). Both serotypes were sensitive to ceftriaxone and vancomycin; one was resistant to penicillin. This is the first study reporting the prevalence of pneumococcal bacteremia since the introduction of PCV13.

                PMID: 23570543 [PubMed - as supplied by publisher]

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17. Ann Emerg Med. 2013 Apr 2. pii: S0196-0644(13)00108-X. doi: 10.1016/j.annemergmed.2013.02.004. [Epub ahead of print]

Emergency Provider Analgesic Practices and Attitudes Toward Patients With Sickle Cell Disease.

Glassberg JA, Tanabe P, Chow A, Harper K, Haywood C Jr, Debaun MR, Richardson LD.

Department of Emergency Medicine, Mount Sinai School of Medicine, New York, NY. Electronic address:



We determine whether emergency provider attitudes and demographics are associated with adherence to national guidelines for the management of acute sickle cell disease pain.


We conducted a cross-sectional survey of emergency providers at the 2011 annual American College of Emergency Physicians Scientific Assembly, using a validated instrument to assess provider attitudes and self-reported analgesic practices toward patients with sickle cell disease. Multivariable, relative risk regressions were used to identify factors associated with adherence to guidelines.


There were 722 eligible participants, with a 93% complete response rate. Most providers self-reported adherence to the cornerstones of sickle cell disease pain management, including parenteral opioids (90%) and redosing opioids within 30 minutes if analgesia is inadequate (85%). Self-reported adherence was lower for other recommendations, including use of patient-controlled analgesia, acetaminophen, non-steroidal anti-inflammatory drugs and hypotonic fluids for euvolemic patients. Emergency providers in the highest quartile of negative attitudes were 20% less likely to redose opioids within 30 minutes for inadequate analgesia (risk ratio 0.8; 95% confidence interval [CI] 0.7 to 0.9). High-volume providers (those who treat more than 1 sickle cell disease patient per week), were less likely to redose opioids within 30 minutes for inadequate analgesia (risk ratio 0.9; 95% CI 0.8 to 0.9). Pediatric providers were 6.6 times more likely to use patient-controlled analgesia for analgesia (95% CI 2.6 to 16.6).


The majority of emergency providers report that they adhere to national guidelines about use of opioids for sickle cell disease-related acute pain episodes. Other recommendations have less penetration. Negative attitudes toward individuals with sickle cell disease are associated with lower adherence to guidelines.

Copyright © 2013. Published by Mosby, Inc.

                PMID: 23561465 [PubMed - as supplied by publisher]

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Sickle Cell News for August  2012

September is Sickle Cell Month – see all the events at the end of the newsletter


Living Well with Sickle Cell

Forty-eight-year-old Ayoola Olajide is living well with sickle cell anaemia (SS). Olajide, the Editor of African Sickle Cell News and World Report, and author of Menace In My Blood- my affliction with sickle cell anaemia is married to a woman with the AA genotype (without the SS trait) and they have three boys (AS, without anaemia but are carriers). Olajide, a journalist, is on a crusade to address the genetic disorder through aggressive public enlightenment.. He said Nigerians with sickle cell could live well into old age if they have the right information and others could avoid having children with the condition by making the right choices.


Affordable Care Act (ACA) by the United States Supreme Court -  SCDAA Summary at

The Sickle Cell Disease Association of America, Inc. (SCDAA) applauds the upholding of many of the provisions of the Affordable Care Act (ACA) by the United States Supreme Court. The ACA represents a significant victory for individuals with chronic diseases such as sickle cell disease. Fear of moving from your pediatric doctor to an adult doctor because you may not have insurance may be unnecessary under the ACA. 

How does the ACA protect you as an individual living with sickle cell disease? SCDAA wants to point out how ACA can improve the healthcare of people with sickle cell disease.  

  1. Insurers can no longer deny coverage to anyone with a chronic or pre-existing health condition such as sickle cell disease. Children and adults are now able to get insurance that covers treatment of their illnesses.
  2. Lifetime caps on coverage have been removed and insurers have to set annual limits on essential health services at a minimum of $750,000. 

What does this mean? This means that health insurance companies cannot deny coverage to anyone with a chronic health condition such as sickle cell disease. Furthermore, your health insurance company can no longer set a limit on how much of your health care costs they will pay forever, this is known as "lifetime cap". Currently, the limit on how much they will pay for your heath care in each year has been set at $750,000. The long-term goal of ACA is to eliminate annual limits that are currently practiced by insurance companies from imposing any annual limits at all. SCDAA will closely monitor and report to you and our member organizations as to the progress the ACA law makes in removing these annual limits completely.


Video Resources

New CDC Videos Posted

Translating Research to Policy Dr. Shawn Bediako, University of Maryland, Baltimore County  at mms://

Schedule of Free CDC 2012 Webinars

“Public Health Webinar Series on Hemoglobinopathies”

Hosted by: The Division of Blood Disorders, National Center on Birth Defects and Developmental Disabilities (NCBDDD), Centers for Disease Control and Prevention (CDC) 4th Thursday of every month from 2:00PM – 3:00PM ET The purpose of this webinar series is to offer a hemoglobinopathies learning collaborative platform for providers, consumers, educators, and scientists.

Hemoglobinopathy Webinars are archived at

To Join The Webinar

Copy this address and paste it into your web browser:

Copy and paste the required meeting ID: 84QK2D and click “join”.

First Time Users: To save time before the meeting, check your system to make sure it is ready to use Microsoft Office Live Meeting. To hear the presentation you must call in to the number below.

For Audio

Dial 1-877-953-6706 and enter participant code: 9706616

If you are unable to join us on the internet for viewing, you are welcome to call in for audio access only. Participants outside the United States must be able to access 800 numbers to the US. Otherwise, please RSVP the location and number of participants for alternative international conference line access.

9/27: Improving Quality of Care for Sickle Cell Pediatrics in the Emergency Department Dr. James Moses, Boston Medical Center 

10/25: Strategies from the Field – Data Collection and Harmonization CDC’s Division of Blood Disorders and RuSH Project States 

November/December: --- No Webinars---

See all the previous CDC Sickle Cell Webinars and instructions to view or listen to future events see:

New Web Resource

NHS Sickle Cell and Thalassaemia Screening Programme Training Modules

Standards are key in the delivery of an expert antenatal and newborn screening programme.  The NHS Sickle Cell and Thalassaemia Screening Programme has invested in a laboratory module where laboratory personnel can participate in online training which tests them on the basic heterozygous conditions which must be detected by the antenatal screening programme.

The module has been designed to incorporate the standards of the Screening Programme’s Laboratory Handbook

See all the publications at

  1. Articles in the Medical Literature for August

    Br J Haematol. 2012 Aug 28. doi: 10.1111/bjh.12019. [Epub ahead of print]

    High dose vitamin D therapy for chronic pain in children and adolescents with sickle cell disease: results of a randomized double blind pilot study.

    Osunkwo I, Ziegler TR, Alvarez J, McCracken C, Cherry K, Osunkwo CE, Ofori-Acquah SF, Ghosh S, Ogunbobode A, Rhodes J, Eckman JR, Dampier C, Tangpricha V.


    Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta, Atlanta, GA, USA; Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.


    We report results of a pilot study of high-dose vitamin D in sickle cell disease (SCD). Subjects were given a 6-week course of oral high-dose cholecalciferol (4000-100 000 IU per week) or placebo and monitored prospectively for a period of six months. Vitamin D insufficiency and deficiency was present at baseline in 82·5% and 52·5% of subjects, respectively. Subjects who received high-dose vitamin D achieved higher serum 25-hydroxyvitamin D, experienced fewer pain days per week, and had higher physical activity quality-of-life scores. These findings suggest a potential benefit of vitamin D in reducing the number of pain days in SCD. Larger prospective studies with longer duration are needed to confirm these effects.

    © 2012 Blackwell Publishing Ltd.

    PMID: 22924607 [PubMed - as supplied by publisher]

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  3. ScientificWorldJournal. 2012;2012:949535. Epub 2012 Aug 1.

    Beyond the definitions of the phenotypic complications of sickle cell disease: an update on management.

    Ballas SK, Kesen MR<, Goldberg MF, Lutty GA, Dampier C, Osunkwo I, Wang WC, Hoppe C, Hagar W, Darbari DS, Malik P.


    Cardeza Foundation and Department of Medicine, Thomas Jefferson University, 1015 Walnut Street, Philadelphia, PA 19107, USA.


    The sickle hemoglobin is an abnormal hemoglobin due to point mutation (GAG → GTG) in exon 1 of the β globin gene resulting in the substitution of glutamic acid by valine at position 6 of the β globin polypeptide chain. Although the molecular lesion is a single-point mutation, the sickle gene is pleiotropic in nature causing multiple phenotypic expressions that constitute the various complications of sickle cell disease in general and sickle cell anemia in particular. The disease itself is chronic in nature but many of its complications are acute such as the recurrent acute painful crises (its hallmark), acute chest syndrome, and priapism. These complications vary considerably among patients, in the same patient with time, among countries and with age and sex. To date, there is no well-established consensus among providers on the management of the complications of sickle cell disease due in part to lack of evidence and in part to differences in the experience of providers. It is the aim of this paper to review available current approaches to manage the major complications of sickle cell disease. We hope that this will establish another preliminary forum among providers that may eventually lead the way to better outcomes.

    PMCID: PMC3415156 Free Article

    PMID: 22924029 [PubMed - in process]

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  5. Blood. 2012 Aug 24. [Epub ahead of print]

    Sickle cell pain: a critical reappraisal.

    Ballas SK, Gupta K, Adams-Graves P.


    Cardeza Foundation, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadephia, PA, United States;


    Sickle cell pain includes three types: acute recurrent painful crises, chronic pain syndromes and neuropathic pain. The acute painful crisis is the hallmark of the disease and the most common cause of hospitalization and treatment in the Emergency Department. It evolves through four phases: prodromal, initial, established and resolving. Each acute painful episode is associated with inflammation that worsens with recurrent episodes, often culminating in serious complications and organ damage such as acute chest syndrome, multi-organ failure and sudden death. Three pathophysiologic events operate in unison during the prodromal phase of the crisis: vaso-occlusion, inflammation and nociception. Aborting the acute painful episode at the prodromal phase could potentially prevent or minimize tissue damage. Our hypothesis is that managing these events with hydration, anti-inflammatory drugs, aggressive analgesia and possibly vasodilators could abort the crisis and prevent or minimize further damage. Chronic pain syndromes are associated with or accompany avascular necrosis and leg ulcers. Neuropathic pain is not well studied in patients with sickle cell disease but has been modeled in the transgenic sickle mouse. Management of sickle cell pain should be based on its own pathophysiologic mechanisms rather than borrowing guidelines from other non-sickle pain syndromes.

    PMID: 22923496 [PubMed - as supplied by publisher]

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  7. Chest. 2012 Aug 20. doi: 10.1378/chest.12-0611. [Epub ahead of print]

    The impact of Sickle Cell Disease on exercise capacity in children.

    Chaudry12 RA, Bush1 A, Rosenthal1 M, Crowley2 S.




    Little is known about pulmonary vascular complications in children with Sickle Cell Disease (SCD). We hypothesised that transfer factor (DLco) may be used as a surrogate for the size of the pulmonary vascular bed, and that pulmonary vascular abnormalities in SCD children may limit exercise capacity.


    50 stable SCD patients aged10 to-18 years and 50 healthy controls matched for race and age were recruited. Incremental ergometer cardiopulmonary exercise testing (CPET) was performed using respiratory mass spectrometry (RMS) for exhaled gas analysis. A rebreathing manoeuvre was used to measure functional residual capacity (FRC), effective pulmonary blood flow (Qpeff) and DLCO, and helium dilution was used to calculate minute ventilation (VE), oxygen consumption (VO2) and carbon dioxide production (CO2).


    In the 89 evaluable subjects, there were no ventilatory differences between SCD and controls. Qpeff was consistently 15-20% greater in SCD than controls at all stages but Dlco corrected for both surface area and haemoglobin was only about 7-10% greater in SCD at all stages As a result the Dlco/Qpeff ratio was considerably lower in SCD at all stages. Arteriovenous oxygen content difference was about one third less in SCD at all stages.


    Contrary to our hypothesis, failure to maintain a sufficient Qpeff to compensate for anaemia led to exercise limitation. The ratio of Pulmonary capillary blood volume to flow is reduced throughout, implying subtle pulmonary vascular disease; however this was not a factor limiting exercise.1Royal Brompton Hospital, London, United Kingdom.2St Georges' Hospital, London, United Kingdom.Corresponding author's details (also author for reprint requests): Dr Mark Rosenthal, Department of Paediatric Respiratory Medicine, Royal Brompton Hospital, London SW3 6NP Email: M.

    PMID: 22922408 [PubMed - as supplied by publisher]

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  9. Blood. 2012 Aug 22. [Epub ahead of print]

    Impact of hydroxyurea on clinical events in the BABY HUG trial.

    Thornburg CD, Files BA, Luo Z, Miller ST, Kalpatthi R, Iyer R, Seaman P, Lebensburger J, Alvarez O, Thompson B, Ware RE, Wang WC.


    Duke University Medical Center, Durham, NC, United States;


    BABY HUG was a Phase III multicenter, randomized, double-blind placebo-controlled clinical trial of hydroxyurea in infants (beginning at 9-18 months of age) with sickle cell anemia (SCA). An important secondary objective of this study was to compare clinical events between the hydroxyurea and placebo groups. One hundred and ninety-three subjects were randomized to hydroxyurea (20 mg/kg/day) or placebo; there were 374 patient-years of on-study observation. Hydroxyurea was associated with statistically significantly lower rates of initial and recurrent episodes of pain, dactylitis, ACS and hospitalization; even infants who were asymptomatic at enrollment had less dactylitis as well as fewer hospitalizations and transfusions if treated with hydroxyurea. Despite expected mild myelosuppression, hydroxyurea was not associated with an increased risk of bacteremia or serious infection. These data provide important safety and efficacy information for clinicians considering hydroxyurea therapy for very young children with SCA. This clinical trial is registered with the NIH (NCT00006400,

    PMID: 22915643 [PubMed - as supplied by publisher]

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  11. Adv Skin Wound Care. 2012 Sep;25(9):420-428.

    Sickle Cell Disease and Leg Ulcers.

    Ladizinski B, Bazakas A, Mistry N, Alavi A, Sibbald RG, Salcido R.


    Barry Ladizinski, MD, BS • Clinical Research Fellow • Duke University Medical Center • Durham, North Carolina Andrea Bazakas, BS • Clinical Trials Assistant II • Duke University Medical Center • Durham, North Carolina Nisha Mistry, MD, BSc, FRCPC(Derm), DABD • Community Dermatologist • Mississauga, Ontario, Canada Afsaneh Alavi, MD, FRCPC(Derm) • Dermatologist and Wound Care Consultant • Women's College Hospital • Toronto, Ontario, Canada R. Gary Sibbald, BSc, MD, Med, FRCPC(Med Derm), MACP, FAAD, MAPWCA • Professor of Public Health and Medicine • University of Toronto • Toronto, Ontario, Canada • Director • International Interprofessional Wound Care Course & Masters of Science in Community Health (Prevention & Wound Care) • Dalla Lana School of Public Health • University of Toronto • President World Union of Wound Healing Societies • Clinical Editor • Advances in Skin & Wound Care • Ambler, Pennsylvania Richard Salcido, MD • Editor-in-Chief • Advances in Skin & Wound Care • Ambler, Pennsylvania • Course Director • Annual Clinical Symposium on Advances in Skin & Wound Care • William Erdman Professor • Department of Rehabilitation Medicine • Senior Fellow • Institute on Aging • Associate • Institute of Medicine and Bioengineering • University of Pennsylvania Health System • Philadelphia, Pennsylvania.


    PURPOSE:: To enhance the learner's competence with knowledge of sickle cell disease (SCD) and its relationship to leg ulcers. TARGET AUDIENCE:: This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. OBJECTIVES:: After participating in this educational activity, the participant should be better able to:1. Demonstrate knowledge of SCD-associated leg ulcer pathophysiology, symptomatology, diagnostic testing, and risk factors.2. Apply knowledge of pain management and treatment options for SCD-associated leg ulcers to patient care scenarios. ABSTRACT: Sickle cell disease is a genetic disorder of hemoglobin synthesis leading to a deformation of the red blood cell. This disorder is associated with painful, slow-to-heal leg ulcers. This article discusses the wound bed preparation paradigm as a guide to the treatment of sickle cell-associated leg ulcers.

    PMID: 22914039 [PubMed - as supplied by publisher]


  13. J Urol. 2012 Aug 16. [Epub ahead of print]

    Priapism is Associated with Sleep Hypoxemia in Sickle Cell Disease.

    Roizenblatt M, Figueiredo MS, Cançado RD, Pollack-Filho F, de Almeida Santos Arruda MM, Vicari P, Sato JR, Tufik S, Roizenblatt S.


    Disciplina de Hematologia e Hemoterapia, Escola Paulista de Medicina, Universidade Federal de Sao Paulo, Brazil.



    We assessed penile rigidity during sleep and the relationship of sleep abnormalities with priapism in adults with sickle cell disease.


    This was a case-control study of 18 patients with sickle cell disease and a history of priapism during the previous year, and 16 controls with sickle cell disease. Participants underwent overnight polysomnography and RigiScan® Plus recording to detect penile rigidity oscillations.


    The priapism group (cases) showed a higher apnea-hypopnea index and oxyhemoglobin desaturation parameters than controls. A lower positive correlation between the apnea-hypopnea index and oxyhemoglobin desaturation time was observed in cases than in controls (Spearman coefficient ρ = 0.49, p = 0.05 vs ρ = 0.76, p <0.01), suggesting that desaturation events occurred independently of apnea. Two controls and 14 cases had a total sleep time that was greater than 10% with oxyhemoglobin saturation less than 90% but without CO(2) retention. Penile rigidity events were observed during rapid eye movement sleep and during stage 2 of nonrapid eye movement sleep, particularly in cases. The duration of penile rigidity events concomitant to respiratory events was higher in cases than in controls. Regression analysis revealed that the periodic limb movement and desaturation indexes were associated with priapism after adjusting for rapid eye movement sleep and lung involvement. Finally, oxyhemoglobin saturation less than 90% was associated with priapism after adjusting for lung involvement, hyperhemolysis and the apnea-hypopnea index.


    Oxyhemoglobin desaturation during sleep was associated with priapism history. It may underlie the distribution pattern of penile rigidity events during sleep in these patients.

    Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

    PMID: 22902014 [PubMed - as supplied by publisher]

    Related citations


  15. Cell Host Microbe. 2012 Aug 16;12(2):187-99.

    Translocation of Sickle Cell Erythrocyte MicroRNAs into Plasmodium falciparum Inhibits Parasite Translation and Contributes to Malaria Resistance.

    Lamonte G, Philip N, Reardon J, Lacsina JR, Majoros W, Chapman L, Thornburg CD, Telen MJ, Ohler U, Nicchitta CV, Haystead T, Chi JT.


    The Institute for Genome Sciences and Policy, Duke University School of Medicine, Durham, NC 27710, USA; Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA; University Program in Genetics and Genomics, Duke University School of Medicine, Durham, NC 27710, USA.


    Erythrocytes carrying a variant hemoglobin allele (HbS), which causes sickle cell disease and resists infection by the malaria parasite Plasmodium falciparum. The molecular basis of this resistance, which has long been recognized as multifactorial, remains incompletely understood. Here we show that the dysregulated microRNA (miRNA) composition, of either heterozygous HbAS or homozygous HbSS erythrocytes, contributes to resistance against P. falciparum. During the intraerythrocytic life cycle of P. falciparum, a subset of erythrocyte miRNAs translocate into the parasite. Two miRNAs, miR-451 and let-7i, were highly enriched in HbAS and HbSS erythrocytes, and these miRNAs, along with miR-223, negatively regulated parasite growth. Surprisingly, we found that miR-451 and let-7i integrated into essential parasite messenger RNAs and, via impaired ribosomal loading, resulted in translational inhibition. Hence, sickle cell erythrocytes exhibit cell-intrinsic resistance to malaria in part through an atypical miRNA activity, which may represent a unique host defense strategy against complex eukaryotic pathogens.

    Copyright © 2012 Elsevier Inc. All rights reserved.

    PMID: 22901539 [PubMed - in process]

    Related citations


  17. Clin Biochem. 2012 Aug 8. [Epub ahead of print]

    High lactate dehydrogenase levels at admission for painful vaso-occlusive crisis is associated with severe outcome in adult SCD patients.

    Stojanovic KS, Steichen O, Lefevre G, Bachmeyer C, Avellino V, Grateau G, Girot R, Lionnet F.


    Assistance publique-hôpitaux de Paris, Hôpital Tenon, Service de médecine interne, Centre de référence de la drépanocytose adulte, Paris, France.



    The aim of this study is to assess biological prognostic factors at the onset of vaso-occlusive crisis (VOC) in adults with sickle cell disease (SCD).


    A monocentric prospective study including all patients admitted for VOC in a reference center for SCD was utilized. We used multivariate logistic regression to find independent predictors of severe evolution, defined by death or a worsening clinical state indicating transfusion or transfer to the intensive care unit.


    Eighty eight patients were included, 63% were women, median age of 23years, and 90% of patients were homozygous SCD, 10% compound heterozygous. VOC became severe in 17 patients. Patients with severe VOC were more frequently males, who also had higher white blood cell (WBC) count, procalcitonin (PCT), and lactate dehydrogenase (LDH) levels. LDH level was the best predictor of the outcome; WBC and PCT had no significant added predictive values when coupled with LDH in multivariable models, even in patients with fever or acute chest syndrome. Severe evolution always occurred when LDH levels were over 4 times the upper limit of the normal range at admission and never occurred when LDH levels were within the normal range.


    Further studies should confirm the predictive value of LDH before its widespread use as a prognostic factor. If it is confirmed, the benefit of preemptive transfusion when LDH levels at admission are very high could be investigated.

    Copyright © 2012. Published by Elsevier Inc.


  19. Sickle Cell Conferences and Events

September 25 – 29, 2012  The Sickle Cell Disease Association of America 40th Annual Conference Baltimore MD

The conference will be held September 25 – 29, 2012 at the Baltimore Marriott Waterfront Hotel in Baltimore, MD. We promise that this will be one of the most educational and empowering events to take place within the sickle cell community!


24-27 September  Annual Sickle Cell and Thalassaemia: Advanced Conference -, London UK.  The programme will provide participants with an overview of the key issues in sickle cell disease including a look at the pathology of SCD, diagnostic testing, the impact of environmental factors and genetic modifiers on disease severity, managing acute and chronic sickle cell crises, and dealing with major complications in patients including stroke, renal, liver and cardiac problems and the treatment options available. Website is: 

The main Guy’s and St Thomas’ NHS Foundation Trust website is:


The full link to the course is:


September 19, 2012  NYC, NY 1st Annual Sickle Cell Disease Therapeutics Conference. The conference is intended to serve as a forum to raise awareness for sickle cell disease and will include presentations from leading companies in sickle cell disease and discussions with experts regarding the latest advancements and future trends for patients. The conference will be held September 19, 2012 in the Cosmopolitan Suite at the Four Seasons Hotel in New York City. Conference sponsors include Theradex Systems, Inc. and Rodman & Renshaw, LLC.

Conference attendees will hear from leaders in the sickle cell disease medical and advocacy communities More information can be found on the conference web site at or on the advertising flyer for the event at

SICKLE CELL ASSOCIATION OF ONTARIO ANNUAL CONFERENCETo be held on September 28th  and 29th 2012 at the Toronto Delta East Hotel

  The Sickle Cell Association of Ontario's mission is to serve the community as a recognized voluntary agency that endeavors to optimize the quality of life for individuals and families with sickle cell disease.

   The Sickle Cell Association of Ontario (SCAO) is a non-profit charitable organization, established in 1981 after it became evident that there was a need to educate the public about sickle cell anemia. Also, to provide moral support to parents and families of children, spouses, other relatives and individuals who suffer from sickle cell anemia.

Sickle Cell Association of Ontario 416 789 2855 Tel 416 789 1903 Fax email

or email visit us on the web

Stephanie Mulkey Annual Sickle Cell Disease Educational Seminar, taking place this September 7 and 8 at the Wallis Annenberg building in Exposition Park, Los Angeles, CA, is available online (click here: 

For Adults Only with Sickle Cell Disease Workshop - Atlanta GA
Date/Time: September 22, 2012 9am - 3pm
Location: Adamsville Recreation Center, 3201 Martin Luther King Jr., Drive, Atlanta 30311

September is National Sickle Cell Disease Awareness Month, and in an effort to raise awareness and educate adults living with the disease, a free, one-day workshop is being held on Saturday, September 22, 2012 from 9:00 a.m. - 3:00 p.m. at the Adamsville Recreation Center in Atlanta, GA.

Sponsored by Georgia Department of Public Health,  Sickle Cell Foundation of Georgia, SPCC Atlanta AHEC, and the Georgia Health Policy Center, this workshop is limited to adult sickle cell patients living in the state of Georgia.  Attendees may be accompanied by a care giver or significant other, however, we will not be able to accommodate children.Participants will hear from healthcare professionals specializing in sickle cell disease as well as people living with the disease. In addition, community resources will be available for workshop participants as well.

For more information, call 404-815-4996.  To register for the workshop, go to
Complimentary continental breakfast and lunch will be provided

West Coast Sickle Cell Nurses Conference Friday, October 26, 2012 Presented by
Children's Hospital Los Angeles
-Improving Outcomes for Children and Adults
with Sickle Cell Disease Location: John Stauffer Conference Room  Children's Hospital Los Angeles  Registration fee: $45.00  5 CEU's Lunch provided

Please note, this is a NURSES ONLY conference.  

For adults and parents, please provide this information     to your nurse or health care provider.     For more information, contact  Trish Peterson at
or Debbie Harris at 

the Cuban Society of Hematology VII National Congress for the Spring of 2013 (May 20-24) at the Havana International Conference Center, under the name of HEMATOLOGIA 2013. Toghether with this event, we will be celebrating the III Caribbean Conference on Sickle Cell Disease (from CAREST), as well as the IX Latinamerican Meeting on Hematology, Immunology and Transfusion Medicine, the IV International Workshop on Hemophilia, and the III Internatioal Symposium of Regenerative Medicine.



Sickle Cell Anemia research is constantly ongoing. As information becomes available, it will be posted at this location, it can be found at the Cleveland Clinic web site, or you can contact Ira Bragg-Grant at (216) 229-8600 for the latest available research information as it occurs.

Research Articles

For the latest news, visit this website that is updated weekly at

In the News

Events around the world include:

NIH Halts SWiTCH Study

On behalf of the National Heart, Lung, and Blood Institute (NHLBI), we would like to share with you news about a sickle cell disease clinical trial, the Stroke With Transfusions Changing to Hydroxyurea (SWiTCH) study. The multicenter clinical trial compared treatments to reduce the risk of additional strokes while minimizing the adverse effects of treatment such as iron overload in young participants (between the ages of 5 and 19) with sickle cell disease and a history of stroke and iron overload. The study was stopped early because a regular review of the data indicated that the experimental treatment was unlikely to prove better than the standard treatment. The NHLBI issued a press release about the early termination of the study, which can be found at:

The preliminary results of this study support the use of the standard treatment of periodic blood transfusions for reducing the risk of additional strokes in young, high-risk patients combined with deferasirox (EXJADE®), an FDA-approved drug to treat chronic iron overload. The alternative treatment that was tested -- hydroxyurea combined with phlebotomy -- does not appear to be better than this standard treatment.

Protecting study participants is the NHLBI’s priority, and when an experimental treatment fails to meet its predetermined goals, it is best to return participants to standard treatment as soon as possible. The NHLBI remains committed to continuing to support research to identify new or improved ways to reduce the burden of sickle cell anemia’s most severe symptoms on our children.

The results from SWiTCH do not affect the majority of sickle cell disease patients who are currently benefiting from hydroxyurea. NHLBI-supported research has shown that hydroxyurea helps prevent pain crises and some lung complications in adults. Patients currently taking hydroxyurea should continue taking the treatment as prescribed and should talk to their primary care provider if they have any concerns. Please let us know if you have any questions about the study. For scientific questions, please contact W. Keith Hoots, M.D., director of the NHLBI Division of Blood Diseases and Resources, at 301-435-0080.

New Book Published - Sickle Cell Disease - 100 Years Later". by Phyllis Zachery-Thomas

This book provides a transparent look into my personal struggle with sickle cell disease and how it led me to the formation of SCD Soldier Network, Inc. I co-authored the book with Atlanta Historian Dan Moore of the Apex Museum and founder of Marrow for Life. The book also includes the inspiring stories of others who battle the disease as well as it gives you the history of sickle cell and information about the blood disorder. I am very pleased with this project and am asking for your support. Please purchase your copy today, I promise you won't be disappointed. Please see attached flyer or access the website to purchase the book by clicking on the link Fifty percent of the proceeds from the sale of this book will be donated to SCD Soldier Network in order to fulfill it's mission.

Articles in the Medical Literature

  1. Pulmonary hypertension in sickle cell disease children under 10 years of age.
    Colombatti R, Maschietto N, Varotto E, Grison A, Grazzina N, Meneghello L, Teso S, Carli M, Milanesi O, Sainati L.
    Br J Haematol. 2010 Jun 10. [Epub ahead of print]
  2. Moving young people with sickle cell disease from paediatric to adult services.
    Howard J, Woodhead T, Musumadi L, Martell A, Inusa BP.
    Br J Hosp Med (Lond). 2010 Jun 9;71(6):310-314.
  3. Hospital self-discharge among adults with sickle-cell disease (SCD): associations with trust and interpersonal experiences with care.
    Haywood C Jr, Lanzkron S, Ratanawongsa N, Bediako SM, Lattimer-Nelson L, Beach MC.
    J Hosp Med. 2010 May-Jun;5(5):289-94.
  4. High mortality from P. falciparum malaria in children living with sickle cell anemia on the coast of Kenya.
    McAuley CF, Webb C, Makani J, Macharia A, Uyoga S, Opi DH, Ndila C, Ngatia A, Scott JA, Marsh K, Williams TN.
    Blood. 2010 Jun 8. [Epub ahead of print]
  5. Management of Painful Vaso-Occlusive Crisis of Sickle Cell Anemia: Consensus Opinion.
    Mousa SA, Momen AA, Al Sayegh FA, Jaouni SA, Nasrullah Z, Saeed HA, Alabdullatif A, Sayegh MA, Zahrani HA, Hegazi M, Mohamadi AA, Alsulaiman A, Omer A, Kindi SA, Tarawa A, Othman FA, Qari M.
    Clin Appl Thromb Hemost. 2010 Jun 7. [Epub ahead of print]
  6. Depression and loneliness in Jamaicans with Sickle Cell Disease.
    Asnani MR, Fraser RA, Lewis NA, Reid ME.
    BMC Psychiatry. 2010 Jun 7;10(1):40. [Epub ahead of print]
  7. Lactate dehydrogenase as a predictor of kidney involvement in patients with sickle cell anemia.
    Gurkan S, Scarponi KJ, Hotchkiss H, Savage B, Drachtman R.
    Pediatr Nephrol. 2010 Jun 2. [Epub ahead of print]
  8. The risks and benefits of long-term use of hydroxyurea in sickle cell anemia: A 17.5 year follow-up.
    Steinberg MH, McCarthy WF, Castro O, Ballas SK, Armstrong FD, Smith W, Ataga K, Swerdlow P, Kutlar A, DeCastro L, Waclawiw MA; Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia and MSH Patients' Follow-Up.
    Am J Hematol. 2010 Jun;85(6):403-8.
  9. Mortality of children with sickle cell disease: a population study.
    Fernandes AP, Januário JN, Cangussu CB, de Macedo DL, Viana MB.
    J Pediatr (Rio J). 2010 May 27;86(4). [Epub ahead of print]
  10. GMI-1070, a novel pan-selectin antagonist, reverses acute vascular occlusions in sickle cell mice.
    Chang J, Patton JT, Sarkar A, Ernst B, Magnani JL, Frenette PS.
    Blood. 2010 May 27. [Epub ahead of print]
  11. Association of G6PD with lower haemoglobin concentration but not increased haemolysis in patients with sickle cell anaemia.
    Nouraie M, Reading NS, Campbell A, Minniti CP, Rana SR, Luchtman-Jones L, Kato GJ, Gladwin MT, Castro OL, Prchal JT, Gordeuk VR.
    Br J Haematol. 2010 May 9. [Epub ahead of print]
  12. Prevalence and clinical correlates of microalbuminuria in children with sickle cell disease.
    Becton LJ, Kalpatthi RV, Rackoff E, Disco D, Orak JK, Jackson SM, Shatat IF.
    Pediatr Nephrol. 2010 Aug;25(8):1505-11. Epub 2010 May 27.
  13. Dietary Water and Sodium Intake of Children and Adolescents With Sickle Cell Anemia.
    Fowler KT, Williams R, Mitchell CO, Levy MC, Pope LF, Smeltzer MP, Wang WC.
    J Pediatr Hematol Oncol. 2010 May 24. [Epub ahead of print]
  14. A controlled, longitudinal study of the social functioning of youth with sickle cell disease.
    Noll RB, Kiska R, Reiter-Purtill J, Gerhardt CA, Vannatta K.
    Pediatrics. 2010 Jun;125(6):e1453-9. Epub 2010 May 24.
  15. Role of Arginase in Sickle Cell Lung Disease and Hemolytic Anemias Claudia R. Morris The Open Nitric Oxide Journal, 2010, 2, 41-54

Conferences and Activities of Interest to the Sickle Cell Community

Articles in the Medical Literature

Raphael JL, Shetty PB, Liu H, Mahoney DH, Mueller BU.  A critical assessment of transcranial doppler screening rates in a large  pediatric sickle cell center: opportunities to improve healthcare quality. Pediatr Blood Cancer. 2008 Nov;51(5):647-51.
 Wang WC, Pavlakis SG, Helton KJ, McKinstry RC, Casella JF, Adams RJ, Rees RC; BABY HUG Investigators.   MRI abnormalities of the brain in one-year-old children with sickle cell anemia. Pediatr Blood Cancer. 2008 Nov;51(5):643-6.
Moreira-Almeida A, Koenig HG.  Religiousness and spirituality in fibromyalgia and chronic pain patients.  Curr Pain Headache Rep. 2008 Oct;12(5):327-32.
Okumura MJ, Heisler M, Davis MM, Cabana MD, Demonner S, Kerr EA.  Comfort of general internists and general pediatricians in providing care for  young adults with chronic illnesses of childhood. J Gen Intern Med. 2008 Oct;23(10):1621-7. Epub 2008 Jul 26.
Sonati MD, Costa FF.  The genetics of blood disorders: the hereditary hemoglobinopathies.  J Pediatr (Rio J). 2008 Sep 12;84(4 (Suppl)). Full Text PDF
Gold JI, Mahrer NE, Treadwell M, Weissman L, Vichinsky E.  Psychosocial and behavioral outcomes in children with sickle cell disease and their healthy siblings. J Behav Med. 2008 Sep 11.
Mittal H, Roberts L, Fuller GW, O'Driscoll S, Dick MC, Height SE, Thein SL, Rees DC.  The effects of air quality on haematological and clinical parameters in children   with sickle cell anaemia. Ann Hematol. 2008 Sep 4.
Ulug P, Vasavda N, Kumar R, Keir L, Awogbade M, Cunningham J, Rees DC, Menzel  S, Thein SL.   Hydroxyurea therapy lowers circulating DNA levels in sickle cell anemia. Am J Hematol. 2008 Sep;83(9):714-6.
Koch J, Manworren R, Clark L, Quinn CT, Buchanan GR, Rogers ZR.  Pilot study of continuous co-infusion of morphine and naloxone in children with  sickle cell pain crisis. Am J Hematol. 2008 Sep;83(9):728-31.
Rovner AJ, Stallings VA, Kawchak DA, Schall JI, Ohene-Frempong K, Zemel BS.  High risk of vitamin d deficiency in children with sickle cell disease.  J Am Diet Assoc. 2008 Sep;108(9):1512-6.
Palermo TM, Riley CA, Mitchell BA.  Daily functioning and quality of life in children with sickle cell disease pain:   relationship with family and neighborhood socioeconomic distress. J Pain. 2008 Sep;9(9):833-40. Epub 2008 Jun 12.

Ask the Experts

Is delayed puberty an issue for sickle cell patients?

Delayed growth & delayed puberty are very common features of sickle cell disease. Poor nutrition may make the delay worse, and a nutrition consultation may be helpful.  A few centers use supplements of growth hormone or testosterone to help with growth, but decisions to use those hormones need a detailed assessment by a pediatric endocrinologist.  Anti-sickling therapy with hydroxyurea or chronic transfusion are likely to help with growth. Bone marrow transplantation has complex effects on growth and puberty.  I encourage you to discuss these inter-related issues with your son's hematologist, endocrinologist, and nutritionist
Here is the abstract of one recent journal article on this topic.
Pediatr Res. 2007 May;61(5 Pt 1):607-13.

Effects of delayed pubertal development, nutritional status, and disease severity on longitudinal patterns of growth failure in children with sickle cell disease.

Zemel BSKawchak DAOhene-Frempong KSchall JIStallings VA.
Division of Gastroenterology, Hepatology, and Nutrition, The Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Previous studies of children with sickle cell disease (SCD) reported poor growth and delayed maturation. However, the prevalence, magnitude, and correlates of suboptimal growth remain poorly understood. A prospective longitudinal study was undertaken to determine the effects of disease severity and nutritional status on growth, an indicator of childhood well-being. Children, birth to 18 y of age, with SCD-SS were evaluated annually for 4 y. Growth, nutritional status, skeletal and sexual maturation, disease severity, dietary intake, and maternal education were assessed. In this sample of 148 children (78 females), growth in height, weight, or body mass index declined in 84% of subjects; 38% fell below the 5th percentile in one or more measures. Puberty was delayed 1 to 2 y, and median age at menarche was 13.2 y. Skeletal age was delayed by 0.7 +/- 1.4 y overall and by 1.3 +/- 1.5 y in children 10 to 15 y old. Height status declined over time and was positively associated with advancing puberty and hematological measures in girls, and nutritional status in girls and boys. Growth failure and maturational delay remain significant chronic problems in children with SCD-SS and are related to potentially modifiable factors such as nutritional status.
Lewis Hsu, MD, PhD
Pediatric Hematologist
For more frequently asked questions please see:
American Society of Hematology Launches New Campaign to Educate Consumers on Vital Connection Between Blood and Personal Health
Program developed in response to results of national survey indicating most Americans have low awareness of common blood conditions

Dr. Charles Whitten, M.D., associate dean emeritus of the Wayne State University School of Medicine, died Aug. 13. He was 86. 

“Dr. Whitten was a pioneer in the field of medical education,” said Robert Frank, M.D., executive vice dean for the School of Medicine. “He founded the post baccalaureate program at Wayne State University School of Medicine, which was a national model for the inclusion of under-represented minority students in schools of medicine. Dr. Whitten revolutionized the curriculum at our School of Medicine, and was a personal mentor to many of our current medical educators.” 

The post baccalaureate program led to Wayne State University leading the nation’s 125 medical schools (exclusive of Howard and Meharry) in the total number of African-American graduates from 1981 to 1997. One-third of them had entered through his program. 

In addition to developing the post baccalaureate program in 1969, Dr. Whitten formed the Sickle Cell Detection and Information Center, the most comprehensive community program in the country, and facilitated the creation of the National Association for Sickle Cell Disease. 

As chief of Pediatrics at Detroit Receiving Hospital, he was the first African-American physician to head a department in a Detroit hospital. 

Dr. Whitten, who served more than 40 years as a member of the School of Medicine faculty, served 16 years as associate dean for Curriculum before entering semi-retirement in 1993 as professor and dean emeritus. 

“Dr. Whitten was best known for his pioneering work in sickle cell anemia screening and development of novel educational tools for teaching children and families with sickle cell anemia,” said Yaddanapudi Ravindranath, M.B.B.S., professor of Pediatrics and the Georgie Ginopolis Chair for Pediatric Cancer and Hematology at the School of Medicine, and co-director of the Division of Hematology/Oncology for Children's Hospital of Michigan. “His forceful advocacy paved the way for the routine newborn screening for sickle cell anemia in Michigan and later in the United States.” 
Bio at

Ask the Experts

I can not afford the medications prescribed for me, Are there ant programs that can help?

There are some very good programs that help such as
Work with your clinician to see if these programs can help

Which is better erythrocytopheresis or simple blood transfusion for the prevention of childhood stroke?

Nobody has hard data on the number of sickle cell patients in the USA, but the estimate from the Sickle Cell Disease Association of America is 100,000.  The estimate is that 10% of the children with sickle cell disease SS are at risk for stroke and will benefit from chronic transfusion as primary or secondary stroke prevention.

Some studies comparing costs of chronic simple transfusion plus iron chelation vs bone marrow transplant also include erythrocytapheresis.  The costs depend fairly strongly on whether the target HbS is 30percent or 50 percent.

As you know, the use of RBC exchange is far better than simple transfusion in terms of iron overload but requires technical expertise and a good cost structure. When I was practicing in Atlanta, we wrote numerous business plans about setting up sickle cell erythrocytapheresis centers for the many pediatric sickle cell patients. The limiting factors were: 
1) nursing expertise for venous access. Some children requiring erythrocytapheresis may be as young as 2yrs. Not every patient can maintain an indwelling catheter for pheresis, often they get infected or clotted.  The pheresis service needs superb nurses who can place a large-bore peripheral IV in any patient.
2) most insurance companies paid the same amount for erythrocytapheresis as for a simple blood transfusion - which covered costs for neither but was much less favorable from a financial perspective for erythrocytapheresis.
3) greater demand for specially matched PRBC (negative for C, E, Kell antigens and negative for sickle hemoglobin) would strain the Blood Bank supply. Many pheresis units require partnering with a special donor recruitment programs to increase blood donations by African-Americans who are more likely than Caucasians to have RBC that are negative for C, E, Kell.  The PRBC demand depends fairly strongly on whether the target HbS is 30percent or 50 percent.

My impression is that medical centers offering erythrocytapheresis combine it somehow with hemodialysis units or some other service to help break even. Or the medical centers just eat the cost because it is better for the patients and perhaps feature this service as a marketing tool.

Dr. Hae-won Kim at Children's Hospital of Philadelphia has the largest erythrocytapheresis center for sickle cell patients that I have seen. She taught many centers how to set up sickle cell erythrocytapheresis.

Lewis Hsu, MD, PhD
Pediatric Hematologist
For more frequently asked questions please see:

Gaining Ground On Sickle Cell Disease. - Children's Hospital Boston (2008, July 16).  ScienceDaily. Retrieved July 17, 2008, from

Although sickle cell disease is a single-gene disorder, its symptoms are highly variable. In a study published online July 14 by the Proceedings of the National Academy of Sciences, scientists at Children's Hospital Boston and the Dana Farber Cancer Institute (DFCI), in collaboration with the Broad Institute of MIT and Harvard, report five gene variants that could potentially be helpful in predicting sickle cell disease severity, perhaps even leading to better treatment approaches in the future.  The gene variants influence blood levels of fetal hemoglobin (HbF), which are known to affect symptom severity in sickle cell disease--with some patients experiencing frequent, severe pain crises and organ damage, while others are scarcely aware of their disease.

"Our study is a first step towards a better understanding of fetal hemoglobin regulation in patients with sickle cell disease," says Guillaume Lettre, PhD, of the Broad Institute and Children's Hospital Boston, and co-first author on the paper. "But further validation experiments are needed before these findings can become useful in the clinic."  "Eventually, understanding the factors giving rise to heterogeneity in HbF levels might allow us to take severely affected patients and make them more like those with more benign symptoms," adds Vijay Sankaran, co-first author on the paper with Lettre and an MD-PhD student in the laboratory of Stuart Orkin, MD. (Orkin is chair of pediatric oncology at DFCI and a Howard Hughes Medical Institute investigator at Children's.)

In sickle cell disease, a single genetic mutation results in the production of an abnormal type of hemoglobin, the main component of red blood cells. The abnormal hemoglobin molecules tend to form long chains, causing red blood cells to become stiff and sickle-shaped. The distorted cells have difficulty passing through blood vessels and can block the smaller vessels, resulting in severe pain and eventual organ damage as tissues are robbed of their blood supply. The sickle-shaped red blood cells also have a very short lifespan, causing patients to be chronically anemic.

Previous research had established that retaining high levels of another type of hemoglobin--HbF, found at high levels in the fetus--can ameliorate sickle cell disease symptoms. At birth, HbF comprises between 50 to 95 percent of a child's hemoglobin, gradually declining as the switch is made to adult hemoglobin production -- consistent with clinicians' observations that newborns diagnosed with sickle cell disease usually do not become symptomatic until they are about a year old. Population studies in Saudi Arabia and parts of India had identified groups of sickle cell patients with very high levels of HbF and relatively benign forms of the disease, and additional epidemiologic studies led by Orah Platt, MD, chief of laboratory medicine at Children's, showed that HbF is an ameliorating factor. "The more you have, the better off you are," says Sankaran.

Studying 1600 patients with sickle cell disease, the researchers found that previously identified DNA sequence variants in three chromosome locations (small regions on chromosome 2, 6, and 11) were associated with high or low HbF levels. When they added these five variants to a model previously designed by Platt to predict disease severity, which also factors in age, sex, degree of anemia and HbF levels, the model's predictive ability was enhanced.

The findings need to be validated in large, prospective clinical studies, but the researchers are hopeful about the possible future clinical implications of their work. "As we find gene variants that regulate HbF levels or predict severity, we might eventually want to genotype patients for these variants, to get more predictive information on their disease," Sankaran says.

Finally, once this study is validated, understanding how these variants actually affect HbF levels might someday lead to new drugs that do the same thing. "If we can gain better insight into what these variants are doing, we may eventually have better, more targeted therapies for sickle cell disease," adds Sankaran.

Lettre and Sankaran shared first authorship of the paper. Orkin and Joel Hirschhorn, MD, PhD, of Children's and the Broad Institute, were senior authors.This study was funded by grants from the National Heart, Lung and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, and the Howard Hughes Medical Institute.
Medicinal use of video games growing, may help pain
By DAVID TWIDDY    The Associated Press

This fall, researcher Carmen Russoniello will hand sickle cell anemia patients video game controllers and see whether playing the games helps them control stress and reduce pain caused by their disease.

Scientists, intrigued by video games' intrinsic ability to distract and focus the mind, have for decades looked for ways to use them to improve health and patient outcomes. Much of the work, however, has dwelt in obscurity as researchers struggled with small study sizes and lingering biases against what many considered a juvenile or even anti-social pastime. Even the video game industry has been unsure of what to make of the research, instead focusing primarily on the enjoyment aspect of game design.

But Russoniello, who has studied the physical and mental effects of recreation for 20 years, believes those perceptions are changing. For example, his sickle cell anemia study will be held in a clinical center operated by the highly selective and influential National Institutes of Health. In addition, insurance companies and a leading philanthropic organization have begun throwing big money behind video game research."Ten years ago, they would have laughed me out of that place," the East Carolina University researcher said. "But there's an acceptance of things. (Video games) aren't panaceas but they have their place and we need to find where that place is."

The Robert Wood Johnson Foundation announced in May that it would provide more than $2 million in grants for a dozen studies on the use of computer games for health. The projects range from using active video games, such as the Nintendo Wii, to encourage weight loss in children to seeing whether playing a driving-type video game improves cognitive and visual functions in senior citizens.This year's Games for Health conference, an annual get-together for medical scientists to review the latest in games-related research, drew more than 320 attendees, up from 120 when the meetings began four years ago, said co-founder Ben Sawyer.Among those attending this year's conference were representatives of such major health care organizations as Humana Inc., Cigna Corp. and Kaiser Permanente, which have all launched gaming projects in the past year.

Cigna, for instance, is distributing copies of the HopeLab-developed game ReMission to oncologists to give to their teenage cancer patients. The sci-fi shooter lets players blast cancer cells while learning how the disease progresses and what they can do to improve their health and well-being."Frankly, teens are a difficult group to reach," said Joe Mondy, assistant vice president of IT communications. "We think a video game approach reaches those kids where they are."

As happens in other areas of health, the research is actually trailing behind public behavior.A recent customer survey by Seattle-based PopCap Games Inc., maker of such casual games as Bejeweled, found that more than 20 percent of respondents identified themselves as having some level of physical or mental disability, and most of those said they used games as part of their therapy.One of those is Gail Nichols, 48, who said she has used video games to combat severe depression since the mid-1990s.The northeast Kansas resident, who said she suffers from post-traumatic stress disorder and other ailments, said she carries a Nintendo DS or Gameboy with her when she travels in case she begins feeling anxious or confused in public.

"If I get stressed out, my service dog is there with me. I'll pull (the game) out of her pack and between her being there with me and sitting there playing the game I won't be so nervous about people around me," Nichols said. "I would hope the medical community will add this to their bag of tricks."
Stem cell transplant for sickle cell disease subject of clinical trial

By Beth Miller

July 11, 2008 -- Children with sickle cell disease often face severe pain, organ damage, recurrent strokes and repeated, prolonged hospital stays. Although there are medical interventions that can lessen the symptoms, there is no cure.

In an effort to change that, researchers at Washington University School of Medicine in St. Louis are leading a nationwide, multicenter clinical trial to determine the effectiveness of transplanting blood stem cells from unrelated donors into children with severe sickle cell disease.

The Phase II clinical trial is led by Shalini Shenoy, M.D., associate professor of pediatrics at Washington University School of Medicine in St. Louis and medical director of the pediatric bone marrow transplant program at St. Louis Children's Hospital, and co-principal investigator Naynesh Kamani, M.D., of Children's National Medical Center in Washington, D.C. Children with severe sickle cell disease who qualify will receive a blood stem cell transplant from either bone marrow or umbilical cord blood to replace their own red blood cells. The trial seeks to enroll 45 patients ages 3-16 with symptoms of severe sickle cell disease, such as strokes, frequent pain or repeated episodes of acute chest syndrome, a painful obstruction of the blood vessels in the lungs.

To prepare to receive blood stem cells from a donor, patients must go through an intense treatment called conditioning to reduce production of their own blood cells and prevent their immune system from rejecting donor cells. For this trial, patients will receive reduced-intensity conditioning that could help them better tolerate the transplant with fewer toxic side effects of conditioning, such as infertility. As part of the trial, researchers will determine if the reduced-intensity conditioning treatment will allow the healthy donor blood stem cells to grow successfully in the patient.

Sickle cell disease is an inherited blood disorder affecting red blood cells, which contain hemoglobin, the substance that carries oxygen from the lungs to all parts of the body. In patients with this disease, red blood cells contain an abnormal type of hemoglobin that causes the normally round, flexible red blood cells to become stiff and sickle- or crescent-shaped. The sickle cells can't pass through tiny blood vessels, which can prevent blood from reaching some tissues and can result in tissue and organ damage, pain and stroke. In addition, sickle cells are short lived and lead to a shortage of red blood cells and anemia.

Sickle cell disease affects about 70,000 people in the United States and occurs in about 1 of every 500 African-American births and 1 of every 1,000 to 1,400 Hispanic-American births. Blood transfusions and bone marrow transplants have been shown to be effective treatments by replacing sickle cells with healthy red blood cells. However, blood transfusions have to be repeated regularly and can cause iron overload. Bone marrow transplants have a 10 percent mortality rate because of the possibility of infections, organ damage or graft-versus-host disease as donor cells work against the patient.

A healthy sibling who has the same tissue type as the patient is the best donor for a blood stem cell transplant, but few patients have such a suitable donor in their family. "So using unrelated donors who are close matches is the next best option if transplant is to be considered for this disease," Shenoy says. "Though, the probability of finding a good match is lower for minorities due to fewer minority donors registered in the National Marrow Donor Program, we think we can certainly find a good match for several of our patients," Shenoy says.

Physicians should only consider stem cell transplantation in children with severe cases of sickle cell disease and who have a closely matched donor, according to Shenoy."You only take a patient to transplant if the risk/benefit ratio is better by offering them the transplant," she says. "Right now, blood stem cell transplant is the only potential curative therapy for severe sickle cell disease."

In the preliminary trial, about 10 patients with sickle cell disease nationwide had successful blood stem cell transplants. The promising results generated interest in expanding the trial to a larger group of patients."For a successful outcome we need the red blood cells from the patient to be replaced by donor red cells without complications such as major graft-versus-host disease or organ damage," Shenoy says. "We think we have a good chance. If the donor red cells are rejected, we expect that the patient will recover his or her own red cells and remain at baseline with the disease."

The trial is supported by the Bone Marrow Transplant Clinical Trials Network of the National Heart, Lung, and Blood Institute, the National Marrow Donor Program, the Sickle Cell Disease Clinical Research Network and the Pediatric Blood and Marrow Transplant Consortium.

For more information about participating in the trial or about becoming a donor, contact Shenoy or Yvonne Barnes at (314) 454-6018 or visit the Bone Marrow Transplant Clinical Trials Network Web site at
Sickle Cell Drug Underused by Physicians-  Review of data on hydroxyurea shows it works, but long-term effects are unknown
Posted June 20, 2008

FRIDAY, June 20 (HealthDay News) -- A drug that has shown some effectiveness in treating sickle cell anemia is not being used often enough by doctors who are uncertain about its proper use and possible long-term effects, according to a new report.

Researchers at Johns Hopkins University say their extensive review of studies on hydroxyurea clearly shows its helps people with sickle cell anemia, an inherited disorder that affects mostly people of African and Hispanic heritage. Their report, published in the June 17 Annals of Internal Medicine, concluded that hydroxyurea is a viable treatment option for now, but more quality research is needed.

About 70,000 people in the United States have sickle cell anemia, in which sickle-shaped blood cells periodically clump inside blood vessels, blocking circulation. This results in severe anemia, an increased risk of infections or strokes, and extreme episodes of pain that last for days.

The U.S. Department of Health and Human Services asked Johns Hopkins researchers to examine all previously published studies on hydroxyurea in an effort to increase awareness about the drug's potential.

"We know that many people with sickle cell disease aren't being offered this drug, which is the only one we have to treat this disease," Dr. Sophie Lanzkron, director of the Sickle Cell Center for Adults at Johns Hopkins, said in a prepared statement.

The team analyzed 246 quality articles on the drug and concluded it clearly works. The data suggests that once patients started taking hydroxyurea:

    * Their episodes of painful sickle cell "crises" fell by 68 percent to 84 percent.
    * Their hospital admissions declined by 18 percent to 32 percent.
    * Their levels of fetal hemoglobin, a blood component that appears to eases sickle cell symptoms, increased by 4 percent to 20 percent.

The review also found hydroxyurea impairs sperm development in mice and may do the same in humans. The team, though, could not conclusively back theories that hydroxyurea increased or decreased the risk of leukemia or other tumors, leg ulcers and pregnancy complications from its review.

"It's clear from our literature review that hydroxyurea works, but we need to do much more work to understand how it works and the best ways to use it," Lanzkron says
Natural conception yields perfect match for transplant

Andrea W. Dilworth • Special to The Clarion-Ledger • July 15, 2008

Tammy and Anthony Witherspoon of McComb, both carriers of the sickle cell trait, were hesitant to bring another child into the world because of the 25 percent chance their offspring would be born with the genetic blood disease.

But when they learned son Anthony II's best chance for a cure was the umbilical cord blood of a healthy sibling, they decided to try in vitro fertilization, which they hoped would give them the opportunity to selectively implant an egg that was both free of sickle cell and a match.

"I had to cure my son," said Tammy, director of the Adolescent Offender's Program for the McComb School District.She mentioned it to Dr. Gail Megason, professor of pediatrics and director of the Division of Pediatric Hematology Oncology at the University of Mississippi Medical Center."Her words to me were, 'Bring me a healthy baby, a match.' So we did," Tammy said.

But it wasn't that simple. The in vitro fertilization, which cost the Witherspoons $12,000, was unsuccessful. The day of the scheduled implantation, Tammy and Anthony were told none of the 10 eggs doctors had retrieved from her had survived. Devastated but fertile from the medication she been taking to boost her fertility for implantation, Tammy and Anthony decided to "go home and do it the godly way. We put our faith in God and conceived the same day."

Nine months later, Amani (Swahili for faith in God) was born. Not only was he free of sickle cell, but he was a perfect match for Anthony II.Cord blood transplants are often the only option for patients with sickle cell, which primarily strikes African Americans, Megason said.

"We can find cord blood sometimes easier. It's harder finding a match for African-American patients because they are not on the national registry. It's just a cultural fear."The Witherspoons arranged to have Amani's umbilical cord blood collected by Viacord, a private cord blood bank. Months before her due date, Viacord sent the cord collection kit to the Witherspoons, who in turn took it with them to the hospital when Tammy was ready to deliver.

After Amani's delivery, doctors collected the cord blood, and a representative from Viacord picked it up for processing and storage, which takes six to eight weeks.Private banks usually charge $1,500 to $2,000 to collect, process and store units, but because of the Witherspoons' pre-existing need, their fees were waived.Anthony II wasn't able to undergo the transplant right away, though. Doctors needed to extract bone marrow from Amani to serve as a boost during the cord blood transplant, Tammy Witherspoon said. Amani had to be at least a 1-year-old for the procedure. It was a long wait, but well worth it.

Three years later, at 13, there are no signs of sickle cell anemia in Anthony II's blood, Tammy said."He is the healthiest one in the house. Every mother's dream is to have a healthy kid."

Megason does not recommend that all expectant parents make plans to bank their newborn's cord blood for private use.The Witherspoons, however, are a special case."For patients who have a child with sickle cell, leukemia or other genetic diseases that can be cured by transplantation, if you already have a child with such a disease, you would want to collect cord blood," Megason said.
National guidance issued on treating sickle cell in England

* Published: 09 July 2008 12:25 Author: Alice Coubrough

The standards, published by the Sickle Cell Society,   include guidelines for nurses in primary care as well as specialist networks for hospitals and clinics. The guidance deals with topics such as the management of chronic and acute conditions, blood transfusions, and screening.

Dr Allison Streetly, programme director for the NHS Sickle Cell and Thalassaemia Screening Programme, said: 'The introduction of these much needed national guidelines on caring for adults with the disease is greatly welcome.'Together with the care standards for thalassaemia they lay the foundation for a care framework where patient needs are properly understood both close to where people live and in specialist centres,' she added.

With sickle cell being one of the most commonly inherited genetic diseases in England, the charity said its next challenge would be to improve understanding of sickle cell and thalassaemia among both the public and healthcare professionals.  The standards coincide with Sickle Cell Awareness Month, which has activities running across the country throughout July to improve awareness and management of the disease.

Dr Lorna Bennett, Chairperson, Sickle Cell Society said: ' The reality is that provision of care for adults with sickle cell disease can vary significantly between individual professionals as well as health care provision organisations. These standards are the tool needed to address the inequalities in provision and access to good quality care.' The full text PDF guide book can be downloaded at 
New Center for Sickle Cell Disease Research, treatment, care to be brought together

By Katerina Pesheva Johns Hopkins Medicine

Johns Hopkins Children's Center has received a nearly $5 million grant from the National Heart, Lung and Blood Institute to establish a basic and translational research center for sickle cell disease that will consolidate research, treatment and care of adult and pediatric patients under one roof and speed up the translation of scientific discovery from bench to bedside. In addition, the center will offer counseling and education services to patients and their families.

Sickle cell disease is an inherited blood disorder marked by a mutation in the hemoglobin genes. The defect causes oxygen-starved, abnormal crescent-shaped red blood cells that give the disorder its name. The sickle-shaped cells get stuck in blood vessels, leading to excruciatingly painful strokes and organ damage. Sickle cell anemia affects nearly 72,000 Americans, primarily African-Americans.

"This center will be a marriage of all aspects of science and treatment, from basic science and clinical research to patient care and public health research, all part of the quest to treat and ultimately cure sickle cell disease," said lead investigator James F. Casella, Rainey Professor and chief of Pediatric Hematology at Johns Hopkins.

By drawing on the expertise of researchers from diverse areas, the center's faculty and staff expect to advance promising therapies more rapidly. For example, a basic-science project led by Allen Everett, a pediatric cardiologist, will use the science of proteomics, the study of proteins, to look for biomarkers involved in silent strokes, which are a leading cause of neurologic complications in sickle cell patients. Discoveries in this area will ultimately lead to better understanding, earlier diagnosis, treatment and prevention of neurovascular problems in sickle cell patients.

On the public health end of the spectrum, researchers from the Johns Hopkins Bloomberg School of Public Health, led by Cynthia Minkovitz, will examine how local public health services affect disease course and survival, and then pinpoint public health measures that will help eliminate state-to- state disparities in patient outcomes.

The translational arm of the center, led by urologist Arthur Burnett, will help take lab discoveries to the patient's bedside. For example, scientists will study the role of nitric oxide in sickle cell priapism, long-lasting painful erections that are a common complication of the disease. Researchers will then examine whether certain medications that affect nitric oxide levels might reduce and prevent this dreaded complication, which often requires treatment at the emergency room or hospitalization.

The center will also support a faculty scholar in sickle cell disease and a summer program in sickle cell disease research for high school students.Other partners on the grant include the University of Alabama, which, like Johns Hopkins, has a long history of sickle cell disease research and care. In February, The Johns Hopkins Hospital opened an urgent care center that specializes in treating sickle cell patients experiencing acute pain. In 2000, Hopkins opened an adult sickle cell disease center that focuses on chronic care.

New hope for bone marrow patients -  An advance in stem cell research could one day give hope to patients in need of bone marrow transplants or blood transfusions, scientists have said.

Edinburgh experts used blood stem cells from mice to mimic how humans produce the stem cells and found they were able to multiply them by 150 times. They hope their findings will lead to efficient production of blood stem cells in the laboratory. They could then multiply in the body to renew a patient's blood supply.

The body generates billions of blood cells every day, which are produced by blood stem cells in the bone marrow tissue. These include red blood cells, which deliver oxygen to different organs, and white blood cells, such as lymphocytes and macrophages, which play an important role in the body's immune system.

The University of Wisconsin Pain & Policy Studies Group (PPSG) Releases new Documents for Pain Management

· Achieving Balance in Federal and State Pain Policy: A Guide to Evaluation (Fifth edition),

· Achieving Balance in State Pain Policy: A Progress Report Card (Fourth edition)

These resources are part of the PPSG’s continuing pain and public policy research program. 

The Evaluation Guide is the fifth in a series of evaluations of federal and state pain policies. The Progress Report Card quantifies state pain policies, and tracks progress to promote pain management and reduce policy barriers by comparing 2008 state policy grades with those from 2000, 2003, 2006, and 2007. These two reports are important tools that can be used by government and non-government organizations, as well as policy-makers, healthcare professionals, and advocates to understand the policies in their state that reinforce the right to pain management, or that can hinder patient access to effective treatment.

Visit the PPSG website at to view or download these reports, as well as a national press release, Frequently Asked Questions, and a summary of grade changes
Texas Program targets sickle cell disease

Desmond Woods tried to tough it out the morning he woke up with pain pulsating through his body. But by that night, he could no longer stand what is a common and debilitating effect of sickle cell disease.

"It’s like being stabbed over and over," said Woods, 27, of Fort Worth. "All my joints were just aching, and I was in tears crying because of the pain."

Like other adults with the disease, Woods has been in and out of hospitals searching for relief. Getting care can be difficult. Some medical workers "don’t even know what sickle cell is all about," he said. To address the concern, Harris Methodist Southwest Hospital is spearheading a program to close the gap in care for adults with sickle cell disease. Tarrant County Public Health, the Sickle Cell Disease Association and several area hospitals are also working on the project.

Goals include:

    * Reducing quick-fix emergency-room visits by helping patients better manage pain.
    * Putting protocols in place so patients get aggressive care as soon as they arrive in the emergency room.
    * Encouraging all Tarrant County hospitals to adopt the protocols.
    * Developing a day clinic and finding physicians to manage the patients.

In Texas, infants are screened for the disease and children receive care through pediatric specialists, said Mary Robinson, vice president of patient care services at Harris Methodist Southwest. But access to care changes when patients turn 18. Tarrant County has several comprehensive pediatric programs for children with sickle cell disease, said Linda Humphries, clinical nurse specialist at Harris Methodist Southwest. But once those children grow up, they tend to fall through the cracks.

"They’re not finding consistent care, so they start using the ER as their source of treatment for sickle cell," she said. Along with acute pain in their joints and backs, patients often are dehydrated when they arrive at the hospital. The kidneys, spleen, liver and other organs can be damaged. Pneumonia, urinary tract infections, gallstones and joint destruction can lead to lengthy hospitalizations. "This year I’ve been hospitalized at least four or five times," Woods said.

By teaching adults to identify triggers — including stress, infection and weather changes — the hope is they will be better able to manage their disease and avoid hospitalizations, Robinson said. When patients do end up at the hospital, knowing how to treat them aggressively will also make a difference.

Decades ago, many sickle cell patients did not reach adulthood; today, many live to their 40s. "They are surviving longer and they are still leading productive lives," Humphries said.

New Pain Advocacy Resource at

Sickle Cell Disease is featured in In the Face of Pain®, a new online advocacy toolkit designed to help healthcare professionals and patient advocates achieve greater awareness and understanding of undertreated pain as a serious national health problem.   

In the Face of Pain is an interactive toolkit that enables advocates to create individualized action plans, educational materials, and presentations tailored to a specific pain-related topic.  The toolkit – which can be accessed at – serves as a one-stop location for pain-related statistics and provides guidance on implementing advocacy outreach through various channels, including:

    * Legislative
    * Media
    * Community groups
    * Professional organizations

“We hope this toolkit will be a valuable resource for patients, caregivers and healthcare professionals as they work to alleviate unnecessary suffering and improve pain care practice and policy through education and advocacy,” said Pamela Bennett, RN, BSN, Executive Director, Healthcare Alliance Development at Purdue Pharma L.P., which developed the In the Face of Pain Online Advocacy Toolkit.
Caution a must for athletes with sickle-cell trait,0,564522.story

Athletes who possess the sickle-cell trait can play competitive sports but should be monitored by trainers if they participate in intense workouts, according to guidelines published by both the NCAA and the National Athletic Trainers Association.

The Orange County medical examiner found that symptoms associated with sickle-cell trait caused UCF football player Ereck Plancher to collapse and die after an off-season workout on March 18.

The 2008-09 NCAA Sports Medicine Handbook urges athletic trainers to exercise caution when supervising athletes diagnosed with the blood disorder, as UCF officials confirm Plancher was in 2007. Sickle-cell trait can hamper the ability of cells to carry oxygen when triggered by physical stress, a condition called sickling.

"The harder and faster athletes go, the earlier and greater the sickling," the handbook states. "Sickling can begin in only two to three minutes of sprinting, or in any other all-out exertion of sustained effort, thus quickly increasing the risk of collapse. Athletes with sickle-cell trait cannot be conditioned out of the trait and coaches pushing these athletes beyond their normal physiological response to stop and recover place these athletes at an increased risk of collapse."
Even the most fit athletes with the trait can experience a collapse, the NCAA warns.

Plancher is the 10th athlete between the ages of 12 and 19 to die after intense physical exertion from complications related to sickle-cell trait, according to NATA, which in 2007 released a "consensus statement" in which it warned trainers across the country that athletes with the sickle-cell trait were at risk during "intense exertion." Scott Anderson, head athletic trainer at the University of Oklahoma and co-chair on the task force that produced the NATA statement, said there was a lack of knowledge about the trait within the athletic population so the goal was to educate across the board. NATA suggests screening athletes for the trait and says 64 percent of Division I-A schools who responded to a survey do test for it. UCF is among those schools.

Also see,0,1811971.story,0,7380501.story

Ereck Plancher's death has been linked to a single genetic flaw that millions of Americans share.  It's called sickle-cell trait, and many of those who have it never know they do. That's because it rarely causes symptoms and is not even considered a medical condition or disease.

Yet an expert said Friday that some people with sickle-cell trait are vulnerable to sudden death under severe stress -- such as heat, physical exertion and dehydration. The reasons are not clear, however, and doctors say most with the trait have nothing to fear.

"It only very rarely leads to problems -- it's almost always benign," said Dr. James R. Eckman, an expert in sickle-cell trait and a professor of hematology and oncology at Emory University in Atlanta. "But under the extremes of human endurance, there can be problems. People need to understand this is a very unusual situation." There is one important caveat: Those with the trait can pass the errant gene on to their children. And if both parents have it, they have a one-in-four chance of having a child with full-scale sickle-cell disease. That's why African Americans and people in other risk groups are encouraged to find out whether they carry the gene. Beyond that, Eckman said, those with the trait do not have medical concerns in most circumstances.

One exception may be under extreme physical duress. Eckman said research suggests that exertion, dehydration and heat may trigger the distortion of red blood cells that can impede flow and starve organs of needed oxygen. But he said that risk is very small and can be reduced even further if athletes take basic precautions by drinking plenty of fluids and not overdoing it. And that's good advice for everyone -- even those without sickle-cell trait.

"Again, this is very rare," Eckman said. "In most cases, a person with sickle-cell trait does not have any symptoms, and they should be able to participate in all sports."
Sickle: A sickle crisis? (2008)

A Health outcomes study group in England, NCEPOD, was pleased to undertake a review of current haemoglobinopathy mortality, to obtain broad baseline data and make recommendations to alter practice. In this way, we hope to contribute to improving the quality of life of patients – whose numbers and attendances at health care centres are inevitably going to increase. A Full text PDF of the report and summary slides are available at

New Grant RFP

Title: Meetings, Conferences, and Networks for Research Partnerships to Improve Functional Outcomes (R13)

Details at


In 2004, the NIH Rehabilitation Coordinating Committee developed a program announcement (PAR-04-077) entitled  “Research Partnerships to Improve Functional Outcomes” in order to stimulate multi-disciplinary research into the difficult problems of chronic disease and rehabilitation  The goal of this initiative was to encourage applicants with clinical expertise in rehabilitation or management of chronic disease to partner with scientists outside their fields to develop innovative approaches to problems.  Although the announcement did generate a number of responsive applications across a wide scope of research problems, most applicants had significant difficulties in articulating how the expertise of their teams would actually go about addressing their chosen problems.  In other words, applicants were successful in recruiting appropriate multi-disciplinary teams, but not in working with them to forge coherent research plans.


The present FOA attempts to address this problem by supporting meetings and workshops to bring together investigative teams to facilitate the process of developing appropriate research plans.  We seek to help investigators who have the same interests in solving particular problems of rehabilitation and chronic disease, including mental disorders, and who have complementary research or clinical expertise and/or resources team up and form partnerships to coordinate, exchange, and disseminate information or to explore or clarify a defined subject, problem or area of knowledge.  Proposed workshops and conferences should especially address issues in research methodology, including (but not limited to) selection of appropriate subjects, sample size, subject recruitment, measurement, trial design, and analytic strategies.  It is anticipated that these workshops and conferences will help investigators become successful in submitting competitive applications for investigator-initiated research projects in the future.

Articles in the Medical Literature

Adams-Graves P, Lamar K, Johnson C, Corley P. Development and validation of SIMS: an instrument for measuring quality of life
of adults with sickle cell disease. Am J Hematol. 2008 Jul;83(7):558-62.

Streetly A, Clarke M, Downing M, Farrar L, Foo Y, Hall K, Kemp H, Newbold J, Walsh P, Yates J, Henthorn J.  Implementation of the newborn screening programme for sickle cell disease in England: results for 2003-2005. J Med Screen. 2008;15(1):9-13.

Zempsky WT, Loiselle KA, McKay K, Blake GL, Hagstrom JN, Schechter NL, Kain ZN. Retrospective evaluation of pain assessment and treatment for acute vasoocclusive episodes in children with sickle cell disease. Pediatr Blood Cancer. 2008 Aug;51(2):265-8.

Taori KB, Chaudhary RS, Attarde V, Dhakate S, Sheorain V, Nimbalkar P, Wasnik PN. Renal Doppler indices in sickle cell disease: early radiologic predictors of renovascular changes. AJR Am J Roentgenol. 2008 Jul;191(1):239-42.

Klings ES, Anton Bland D, Rosenman D, Princeton S, Odhiambo A, Li G, Bernard SA, Steinberg MH, Farber HW. Pulmonary arterial hypertension and left-sided heart disease in sickle celldisease: clinical characteristics and association with soluble adhesion molecule expression.cAm J Hematol. 2008 Jul;83(7):547-53.

Field JJ, Glassberg J, Gilmore A, Howard J, Patankar S, Yan Y, Davies SC, Debaun MR, Strunk RC. Longitudinal analysis of pulmonary function in adults with sickle cell disease. Am J Hematol. 2008 Jul;83(7):574-6.

Lanzkron S, Strouse JJ, Wilson R, Beach MC, Haywood C, Park H, Witkop C, Bass EB, Segal JB. Systematic review: Hydroxyurea for the treatment of adults with sickle cell disease. Ann Intern Med. 2008 Jun 17;148(12):939-55. Epub 2008 May 5. Full Text

Brawley OW, Cornelius LJ, Edwards LR, Gamble VN, Green BL, Inturrisi C, James AH, Laraque D, Mendez M, Montoya CJ, Pollock BH, Robinson L, Scholnik AP, Schori M. National Institutes of Health Consensus Development Conference statement: hydroxyurea treatment for sickle cell disease. Ann Intern Med. 2008 Jun 17;148(12):932-8.

Harban FM, Connor P, Crook R, Bingham R. Cardiopulmonary bypass for surgical correction of congenital heart disease in children with sickle cell disease: a case series. Anaesthesia. 2008 Jun;63(6):648-51. Epub 2008 Feb 29.

Alvarez O, Lopez-Mitnik G, Zilleruelo G. Short-term follow-up of patients with sickle cell disease and albuminuria. Pediatr Blood Cancer. 2008 Jun;50(6):1236-9.

Singh SA, Koumbourlis AC, Aygun B. Resolution of chronic hypoxemia in pediatric sickle cell patients after treatment with hydroxyurea. Pediatr Blood Cancer. 2008 Jun;50(6):1258-60.

Dyson, SM; Abuateya, H; Atkin, K; Culley, LA; Dyson, SE; and Rowley, DT (2008) Local authorities and the education 

of young people with sickle cell disorders (SCD) in England International Studies in Sociology of Education 18 (1) 47-60. [

ISSN 0962-1214] doi:10.1080/09620210802196168

Abuateya, H; Atkin, K; Culley, LA; Dyson, SE and Dyson, SM (2008) Young People with Sickle Cell Disorder and Education: 

A Knowledge Review Diversity in Health and Social Care 5 (2): 123-135. [ISSN 1743-1913]

Ask the Experts

Are there some famous people with sickle cell disease

All patients with sickle cell disease are heroes, but here are some who are in the public eye

    * Miles Davis, jazz musician.
    * Paul Williams, singer (The Temptations)
    * Georgeanna Tillman, singer (The Marvelettes)
    * Tionne "T-Boz" Watkins, singer (TLC)
    * Prodigy, rapper (Mobb Deep).
    * Hertz Nazaire - Artist

Let us know if there are others.

For more frequently asked questions please see:
Featured Web Links
A recommitment to sickle cell disease research - The NIH agenda full text at

Patient Advocate Foundation at

A New and Improved web site at 

New Pain Advocacy Resource at

Conferences and Activities of Interest to the Sickle Cell Community  Call for abstracts

September 18, 2008 Chicago - Management of Sickle Cell Disease Conference 2008 “ Multidisciplinary Approach” Hilton Oak Lawn- Astoria Ballroom 9333 S Cicero Ave. Oak Lawn IL. 60453 Contact: Jo Ann Allen 312-345-1100.

Friday September 5, 2008 Annual Sickle Cell Golf Classic Ramblewood Golf & Country Club, 200 Country Club Parkway, Mt. Laurel, N.J. Tee Time: 11:00 am
Saturday September 20, 2008 Annual Sickle Cell Seminar Philadelphia International House 3701 Chestnut Street 10:00 am- 4:00 pm.
Saturday September 27, 2008 11th Annual Walter E. Brandon Sickle Walkathon & " Lighten the Load " CD Launch Party Philadelphia Carousel House
Belmont Avenue & North Concourse Drive 8:00 am- 2:00 pm
Saturday September 27, 2008 " Dancing with the Philadelphia Stars " 7:00 - 12:00 pm
For specific information about each event or sponsorship opportunities contact: Sickle Cell Disease Association of America, Philadelphia/ Delaware Valley Chapter215-471-8686 or visit our website at

The Sickle Cell Thalassemia Patients Network , NY, The Sickle Cell Disease Association of America, of Southern, CT  The Sickle Cell Disease Association of America, Philadelphia/Delaware Valley The Donna T. Darrien Memorial Foundation For Sickle Cell Inc. Newark, NJ

Celebrities Isaac Hayes and WBLS DJ Dr. Bob Lee   For more information  E-mail:

Special Guest Speaker: Dr Michael R DeBaun Venue: Governor’s Hall, St Thomas Hospital , London . United Kingdom

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Can Flying High Make you Sick?
By Kate McHugh, Ivanhoe Health Correspondent
ORLANDO (Ivanhoe Newswire) -- Could that turning feeling in your stomach during an airplane flight be something other than nerves?
A new study in The New England Journal of Medicine tested the effects of exposure to high altitudes to see if acute mountain sickness -- a sensation felt by visitors to mountainous areas -- could be experienced by airplane passengers as well.
Researchers found oxygen in the blood decreased by 4.4 percent at 7,000 to 8,000 feet -- the altitude at which acute mountain sickness is experienced. However, only 7.4 percent of the participants reported complaints of mountain sickness. The symptoms were first felt after 3 to 9 hours of exposure to high altitudes.

So why are symptoms different when the altitudes are the same? Michael, Zimring, M.D., and director of the Center for Wilderness and Travel Medicine at the Mercy Medical Center in Baltimore, Maryland, has a theory -- and it's all about exertion.

"When you go up in a plane to 8,000 feet, you're sitting, you're doing nothing, you're not exerting energy, you don't need as much oxygen, so therefore you're not going to have a problem with a couple hour flight with altitude sickness," Dr. Zimring told Ivanhoe. "Whereas when you go up skiing, if you're young and active and healthy, you're going to be exerting yourself right away. That's where you get acute mountain sickness."
Dr. Zimring recommends all travelers drink lots of water to stay hydrated. He also says unhealthy patients with lung cancer, heart disease or sickle cell disease may experience altitude sickness in airplanes as well.

Sickle cell testing for athletes increases MU athletes do not have to be tested, but they can opt for test.

It’s been two years since MU football player Aaron O’Neal died during a voluntary practice at Faurot Field. O’Neal’s death was initially attributed to lymphocytic meningitis by then-Boone County Medical Examiner Valerie Rao. A University Hospital neuropathologist who examined O’Neal’s brain later said sickle cell trait could have played a role.  As a result, the sickle cell trait might factor into the wrongful death lawsuit brought by O’Neal’s parents against 14 current and former members of the athletic department. In the two years since O’Neal’s death, the number of MU student athletes who have asked to be tested for sickle trait has increased tenfold — from five to almost 50. But MU’s athletic department has not instituted mandatory testing for the trait, nor does the NCAA require it. “Testing is still not mandatory, and I don’t think that it is ever going to be mandatory,” said Rex Sharp, MU’s director of sports medicine. “I just don’t see that happening right now.” Sickle cell trait is a condition that can cause red blood cells to logjam in veins and arteries and block the vital flow of oxygen to muscle tissue during strenuous exercise.

Athletic trainers step up efforts to combat sickle cell trait,1,2323976.story?coll=la-headlines-sports-nfl&ctrack=1&cset=true
The National Athletic Trainers Assn., with more than 6,000 in attendance in Anaheim this week, on Wednesday took a first step toward making the athletic field safer for black athletes, as well as others who carry the potentially lethal sickle cell trait.

Having spearheaded a task force that included more than 20 organizations, the NATA recommended that colleges and high schools show greater awareness of the typically benign condition, which poses a grave risk during intense exertion of physical activity.

"You can take a body of athletic trainers, a body of team physicians, a body of family practice physicians, a body of coaches and athletes, if you ask them what are the non-traumatic causes of deaths for athletes, No. 1 they would say cardiac, No. 2 they would say heat stroke, but after that you'd probably get a lot of head scratching," said Scott Anderson, head athletic trainer at Oklahoma and co-chair of the task force. "Sickle cell trait is the third-leading cause of non-traumatic death at the secondary and collegiate level."

The inherited blood disorder ranks just ahead of asthma, the No. 4 killer.
"We have a lot of kids with asthma," said Lou Randall, who coached Riverside North to the Southern Section's Eastern Division football title. His program is comprised of about 60% black athletes and, statistically, would have about seven or eight players with the trait. "As far as I see, there's nothing in the medical history that shows" sickle cell trait. "I could be wrong. I look for what they're allergic to and if they've had any major injuries."
Randall isn't the only one in the dark.

Anderson cited the similarity in deaths of the first college football player to die of sickle cell trait, Colorado sophomore Polie Portier in 1974, and the most recent, Rice freshman defensive back Dale Lloyd in 2006.

"Thirty-two years later, the athlete, the coaches, the athletic trainer didn't know he had it. Nothing's changed," Anderson said. "There was no association with exertion rate and sickle cell trait. There's a lack of awareness of the syndrome or the risk."

Sickle cell trait is the inheritance of one gene for sickle hemoglobin and one for normal hemoglobin. Under extensive exertion, the sickle hemoglobin can change the shape of red blood cells to that of a quarter moon, or the shape of a farmer's sickle.

Although newborn children are screened for the trait, by the time they enter high school they are often unaware of their condition, which is why the NATA recommended secondary institutions and universities consider testing an athlete, Anderson said, essentially "for the cost of a pizza" from certain laboratories.

Over the past seven years, nine athletes — including a 14-year-old female basketball player and two 12-year-olds training for football — have died when their red blood cells began "sickling." The sickle-shaped cells create a logjam in the blood vessels which can lead to collapse from the rapid breakdown of muscles starved for blood.

Deadly sickling can begin in two to three minutes of any all-out exertion, such as running sprints or stadium steps, and poses a grave risk to athletes if they aren't allowed a longer recovery period between repetitions. Lloyd, the Rice football player, died after running 16 sprints of 100 yards.
One of the critical points of the consensus statement was that having the trait should not prevent an athlete from participation, however training should build up slowly with paced progressions. Athletes should ideally work at their own pace, engage in year-round strength and conditioning programs that meet sport-specific demands, and cease activity with the onset of symptoms such as muscle cramping, pain, swelling, weakness, tenderness, the inability to catch one's breath or fatigue.

About 8% of the general African-American population in the U.S. has the trait, and a study showed that 7% of African-American players in the NFL have it. Among those are Devard Darling, wide receiver for the Baltimore Ravens, whose twin brother, Devaughn, a freshman linebacker at Florida State, died of complications from sickle cell trait in 2001. Devard, one of the featured speakers Wednesday, also carries the trait.
"A lot of people who are in position to help, coaches at the secondary level, they aren't aware of the trait, aren't up to date with the protocols, the trauma," Darling said. "You can't bury your head in the sand and think nothing is happening. Kids are dying, and it's time for people to do something about it. Athletic trainers, they have to know. More important, the athletes have to know their bodies and have to know they carry the trait.
"It needs to be on every high school application."

More information is available at

Network Model Predicts Risk of Death in Sickle Cell (Boston) – Researchers from Boston University School of Medicine (BUSM) and Boston University School of Public Health (BUSPH) have developed a method to estimate sickle cell disease severity and predict the risk of death in people with this disease. The study appears online in the June issue of the journal Blood

Recovery Difficult, but New Treatment Gives Teen New Hope
Experimental bone marrow transplant rids girl's body of sickle cell

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