Resources About Sickle Cell Disease

We’ve gathered news articles and medical literature about sickle cell disease (SCD) from various publications. Please see the resources below to learn about SCD and the new treatments being developed.

Cleveland Clinic Trial to Test Gene Therapy as Treatment of Sickle Cell Disease

Novel Study Designed to Correct Genetic Abnormalities of Red Blood Cells

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Cleveland Clinic researchers are enrolling patients in a clinical trial that aims to work toward a cure for sickle cell disease by changing the patient’s genetics. Sickle cell disease, a genetic blood disorder, is a painful and debilitating condition for which there are few approved therapies.
The multicenter study will evaluate the safety and effectiveness of a single dose of EDIT-301, an experimental one-time gene editing cell therapy that modifies a patient’s own blood-forming stem cells to correct the mutation responsible for sickle cell disease.
During the study, patients’ stem cells are collected for gene editing in a laboratory. Patients then are treated with chemotherapy to destroy the remaining bone marrow and make room for the repaired cells, which are infused back into the body. The study will initially enroll 40 adult patients ages 18 to 50 with severe sickle cell disease, with the possibility of expansion to include adolescents. Patients will be monitored closely after treatment for up to two years.
“Gene therapy is an incredible technology that works by replacing or inactivating disease-causing genes,” said Rabi Hanna, M.D., director of the pediatric blood and bone marrow transplant program at Cleveland Clinic and principal investigator of the trial. “In this study, the gene therapy will introduce healthy genes into the body with the goal of correcting genetic abnormalities of red blood cells. By enabling the cells to produce more fetal hemoglobin, this treatment has the potential to cure sickle cell disease in a precise way.”
This is the first time a novel type of CRISPR gene editing technology – known as CRISPR/ CA12 is being used in a human study to alter the defective gene. This technology is a highly precise tool to modify blood stem cell genomes to enable robust, healthy blood cell production.
While there are an estimated 1 to 3 million people in the U.S. who have the sickle cell trait, there are only about 100,000 people with sickle cell disease. Sickle cell trait and the disease are found more often in certain ethnic groups, including African Americans. In the United States, about 1 in 365 African American babies have sickle cell disease.
Sickle cell disease is an inherited blood disorder that leads to the production of abnormal hemoglobin, which is a red protein responsible for transporting oxygen in the blood. Normal red blood cells are round and can move through small blood vessels to deliver oxygen. However, in people with sickle cell disease, the genetic change in DNA causes a chemical alteration in hemoglobin and alters the shape of red blood cells into a sickle, blocking them from passing through narrow blood vessels. They can clog or break apart, which also leads to decreased red blood cell life and increased iron storage in the liver and heart. This can cause conditions such as liver fibrosis, liver failure, stroke, cardiomyopathy, and heart failure along with severe pain.
For most people with the condition, medications can modify disease severity and treat symptoms. However, despite current therapies, the average life of a sickle cell patient is in the mid-‘40s. A blood or marrow transplant can cure sickle cell disease, but the transplant often requires a sibling donor and has the potential for severe graft versus host disease, which is when donor bone marrow or stem cells attack the recipient.
“New treatments are critical for people who have sickle cell disease. Despite the fact that it has been more than 100 years since its discovery there have been only a few medications approved in the last 50 years for sickle cell disease,” said Dr. Hanna. “Until now, we didn’t have the technology to work with to create a possible cure for this devastating disease.”

About Cleveland Clinic

Cleveland Clinic – now in its centennial year – is a non-profit multispecialty academic medical center that integrates clinical and hospital care with research and education. Located in Cleveland, Ohio, it was founded in 1921 by four renowned physicians with a vision of providing outstanding patient care based upon the principles of cooperation, compassion, and innovation. Cleveland Clinic has pioneered many medical breakthroughs, including coronary artery bypass surgery and the first face transplant in the United States. U.S. News & World Report consistently names Cleveland Clinic as one of the nation’s best hospitals in its annual “America’s Best Hospitals” survey. Among Cleveland Clinic’s 70,800 employees worldwide are more than 4,660 salaried physicians and researchers and 18,500 registered nurses and advanced practice providers, representing 140 medical specialties and subspecialties. Cleveland Clinic is a 6,500-bed health system that includes a 173-acre main campus near downtown Cleveland, 19 hospitals, more than 220 outpatient facilities, and locations in southeast Florida; Las Vegas, Nevada; Toronto, Canada; Abu Dhabi, UAE; and London, England. In 2020, there were 8.7 million total outpatient visits, 273,000 hospital admissions and observations, and 217,000 surgical cases throughout Cleveland Clinic’s health system. Patients came for treatment from every state and 185 countries.

Study Identifies Potential Trends in Pediatric Sickle Cell Mortality

A new population-based cohort study of pediatric patients with sickle cell disease found that mortality trends have largely shifted from bacterial infections as a cause to other associated complications, subsequent treatments, or comorbidities.
The study also reported that mortality risk increased as patients began transition to adult care. In the largest and most recent study of mortality in this population, Kristina Lai, MPH, Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta (CHOA), and colleagues reviewed and categorized morality using CHOA’s Sickle Cell Clinical Database for deceased patients.
“Mortality rates and causes of death in children with sickle cell disease have changed significantly over the past several decades,” the team wrote. “With ongoing improvements in standards of care, modern mortality estimates must be updated.”
They obtained information on demographics, sickle cell disease genotype, data and age of death, healthcare utilization, hydroxyurea use, chronic transfusion therapy, and bone marrow transplant. They further abstracted cause of death and history of significant comorbidities from medical records. Overall, Lai and colleagues assessed 3698 patients who were seen from June 2010-June 2020, which accounted for 19,998 person-years.
Of that total, 45 patients (178 person-years) died. The majority (n = 37) were sickle cell anemia genotypes (Hb SS or Hb S β0 thalassemia), followed by Hb SC (n = 5), and Hb S β+ thalassemia (n = 3). In terms of patient demographics, 53% were female, and the average age at death was 12.8 years. Up to 21 (46.7%) of the deceased patients had been treated with hydroxyurea at some point, and 11 (24.4%) had been treated with chronic transfusion therapy.
“During this 10-year period, the crude death rate was 2.3 per 1,000 person-years,” the investigators continued. “The majority of deaths (62%, n=28) were attributable SCD-related causes and corresponded to a cause-specific mortality rate of 1.40 per 1,000 person-years.”
These causes included an acute illness related to sickle cell disease (n = 12), acute bacterial infections (n = 3), complications related to treatment (procedure-related, n = 1; drug-induced hemolytic anemia, n = 2), and complications of bone marrow transfusion (n = 1).
They further noted that the remaining 38% of deaths were attributed to complex non-sickle cell disease comorbidities (n = 16) or accidental trauma (n = 17). Thus, the non-sickle cell disease mortality rate was calculated to 0.85 per 1,000 person-years.
“In comparison, the mortality rate for African American persons age <22 in Georgia from 2009-2018 was 0.9 per 1,000 person-years,” they wrote.
The non-sickle cell disease comorbidities included cancers (n = 3), autoimmune disorders (n= 2), and congenital heart disease (n = 6).
And finally, their analysis showed that of the 10 patients who died at age >19, 8 had either recently transitioned to adult care or had a documented transition plan.
Lai and her team acknowledged that the single healthcare system approach was a major limitation of the study. Therefore, they indicated that future analyses should focus on expanding the cohort to include data from death certificates and the US Centers for Disease Control (CDC) National Death Index.
The study, “10-Year Mortality in Patients with Sickle Cell Disease from a Large Population-Based Cohort,” was published in Blood.

Therapeutic Gene Editing Strategies Using CRISPR-Cas9 for the β-Hemoglobinopathies

J Biomed Res. 2020 Nov 9;1-20. doi: 10.7555/ JBR.34.20200096.

Authors: James B Papizan, Shaina N Porter 1, Akshay Sharma, Shondra M Pruett-Miller

Abstract

With advancements in gene editing technologies, our ability to make precise and efficient modifications to the genome is increasing at a remarkable rate, paving the way for scientists and clinicians to uniquely treat a multitude of previously irremediable diseases. CRISPR-Cas9, short for clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9, is a gene editing platform with the ability to alter the nucleotide sequence of the genome in living cells. This technology is increasing the number and pace at which new gene editing treatments for genetic disorders are moving toward the clinic. The β-hemoglobinopathies are a group of monogenic diseases, which despite their high prevalence and chronic debilitating nature, continue to have few therapeutic options available. In this review, we will discuss our existing comprehension of the genetics and current state of treatment for β-hemoglobinopathies, consider potential genome editing therapeutic strategies, and provide an overview of the current state of clinical trials using CRISPR-Cas9 gene editing.

Keywords: CRISPR; fetal hemoglobin; gene editing; genome engineering; hemoglobinopathy; sickle cell anemia; sickle cell disease.

Trial Design of Comparing Patient-Specific Versus Weight-Based Protocols to Treat Vaso-Occlusive Episodes in Sickle Cell Disease (COMPARE-VOE)

Contemp Clin Trials. 2020 Dec 18;106252. doi: 10.1016/ j.cct.2020.106252.

Authors Stephanie O Ibemere, Sarah B Dubbs, Huiman X Barnhart , Jacqueline L Brown, Caroline E Freiermuth, Patricia Kavanagh, Judith A Paice, John J Strouse, R Gentry Wilkerson, Paula Tanabe

Abstract

Objectives: Painful vaso-occlusive episodes (VOE) are the most common reason for emergency department (ED) visits experienced by patients with sickle cell disease (SCD). The National Heart, Lung and Blood Institute (NHLBI) evidence-based recommendations for VOE treatment are based primarily on expert opinion. In this randomized controlled trial (RCT), we will compare changes in pain scores between patients randomized to a patient-specific analgesic protocol versus those randomized to a weight-based analgesic protocol, as recommended by the NHLBI guidelines.

Methods: We report the rationale and design of a multi-site, phase III, single-blinded, RCT to be conducted in six EDs in the United States. Eligible participants will be randomized after providing consent, anticipating 50% of those randomized would have an ED visit during the enrollment period. A total of 230 participants with one VOE ED visit provides sufficient power to detect a clinically significant difference in pain score reductions of 14 between groups with 0.05 type I error. Uniquely, this trial randomizes participants in a larger population than the study population, given the impossibility of consenting and randomizing participants during emergencies. The primary endpoint is the change in pain scores in the ED from time of placement in treatment area to time of disposition (hospitalization, discharged home, or assigned to observation status) or a maximum treatment duration of 6 h. Additional outcomes include hospitalizations and ED visits seven days post-enrollment, side effects, and safety assessments.

Conclusions: The COMPARE-VOE study design will provide high-level evidence to support the NHLBI VOE treatment guidelines.

Keywords: Clinical trial; Emergency department; Pain management protocol; Sickle cell disease; Vaso-occlusive crisis; Vaso-occlusive episode.

Use of Artificial Intelligence and Virtual Reality Within Clinical Simulation for Nursing Pain Education: A Scoping Review

Nurse Educ Today. 2020 Dec 9;97:104700. doi: 10.1016/ j.nedt.2020.104700.

Authors Joanne Harmon, Victoria Pitt, Peter Summons, Kerry J Inder

Abstract

Objectives: To explore and map the evidence for virtual reality and artificial intelligence in simulation for the provision of pain education for pre and post registration nurses.

Design: A scoping review of published and unpublished research from 2009 to 2019.

Data sources: Nine electronic databases and hand-searching of reference lists.

Review methods: Studies were included if virtual reality or artificial intelligence interventions were used for education on pain care provision in nursing. Data were extracted and charted using an extraction tool and themes were explored using narrative analysis.

Results: The review process resulted in the inclusion of four published studies. All studies used mixed methods and used artificial intelligence within clinical simulations as an intervention. No studies using virtual reality for pain education met the inclusion criteria. Participants of three studies were undergraduate nursing students in universities and participants in the fourth study were registered nurses within a hospital. Outcomes measured were user acceptance of the technology and feasibility in all studies. The context was hospital located and focused on acute pain episodes, with one exception being sickle cell pain. Three studies had adult patients and the other pediatric patients. The exclusion of input from a patient perspective was notable, as was a lack of interdisciplinary involvement.
Conclusion: Nurses are integral to the assessment and management of pain in many care settings requiring comprehensive communication and clinical skills. There is a paucity of research on the use of virtual reality or artificial intelligence in pain education for nurses. Current studies are preliminary in nature and/or pilot studies. Further empirical research with robust design is required to inform nursing education, practice, and policy, thereby supporting the advancement of nursing pain education.

Keywords: Artificial intelligence; Assessment; Education; Management; Nursing; Pain; Simulation.

Copyright © 2020 Elsevier Ltd. All rights reserved.

Crizanlizumab in Vaso-Occlusive Crisis Caused by Sickle Cell Disease

Drugs Today (Barc). 2020 Nov;56(11):705-714. doi: 10.1358/ dot.2020.56.11.3178111.

Author R V Gardner 1

Abstract

Sickle cell disease (SCD) is a genetic disorder characterized by a single gene mutation leading to polymerization of erythrocytes, with subsequent assumption of a “sickle” shape. However, polymerization is just one aspect of the disorder’s pathology. It is also characterized by abnormalities in nitric oxide utilization and vasculopathy; generation of reactive oxygen species; hemolysis; hypercoagulability; and altered rheology including abnormal leukocyte rolling along endothelium, and sickle cell-endothelial and cell-cell adhesion. The latter phenomenon is associated with increased P- and E-selectin expression and creation of a proadhesive endothelial environment. The anti-P-selectin humanized monoclonal antibody crizanlizumab functions through selective inhibition of P-selectin. At a dose of 5 mg/kg in a clinical trial, it led to a 45.3% decline in the median annual crisis rate in individuals with SCD. Tolerability was good and the adverse event profile was acceptable. In this review, results of the clinical trials involving this drug and specific side effects are outlined. Analysis of cost efficacy is touched on, with an examination of the economic and social burden of SCD.

Keywords: Anemia; Blood disorders; Crizanlizumab; Monoclonal antibodies; P-selectin inhibitors; Sickle cell disease; Vaso-occlusive crisis.

Copyright 2020 Clarivate Analytics.

Exploration of Barriers and Facilitators to Optimal Emergency Department Care of Sickle Cell Disease: Opportunities for Patient-Physician Partnerships to Improve Care

Hemoglobin. 2020 Dec 17;1-12. doi: 10.1080/ 03630269.2020.1859383. Online ahead of print.

Authors Zachary Liederman 1 2 , Naa Kwarley Quartey 3 , Richard Ward 1 2 , Janet Papadakos 3 4 5

Abstract

Sickle cell disease patients commonly present to an emergency department (ED) due to acute Vaso-occlusive pain episodes (VOEs), also known as Vaso-occlusive crises (VOCs). Unsatisfactory patient care leads to preventable morbidity, mortality, and substantial financial costs. This study investigated the current use of sickle cell disease patient-directed physician education (PDPE) in the clinical setting and also explored opportunities for improvement. A qualitative phenomenologic design was used with semi-structured in-depth interviews. Open-ended questions were used to probe participant’s experiences with EDs, the feasibility of a PDPE program as well as barriers and facilitators to PDPE. A total of nine patients and eight physicians participated in the study. Three major themes were identified: divergent challenges to patient recommendations, new targets for sickle cell disease education and triage process: not heard and not seen. Numerous challenges exist to the implementation and optimization of PDPE with sickle cell disease triage processes and nursing support identified as influential factors. Paramount to the process of improving PDPE is physicians perceiving patients as credible sources of information, especially as it relates to generalized concerns of opioid dosing. A patient provided written or digital education tool can be considered to facilitate PDPE to ease communication strain on patients while increasing communication efficiency.

Keywords: Patient education; medical education; sickle cell disease.

Developmental Profile of Sleep and Its Potential Impact on Daytime Functioning From Childhood to Adulthood in Sickle Cell Anaemia

Brain Sci. 2020 Dec 14;10(12):981. doi: 10.3390/ brainsci10120981.

Authors Melanie Kölbel 1 , Fenella J Kirkham 1 2 3 4 , Dagmara Dimitriou 5

Abstract

Young individuals with sickle cell anaemia (SCA) experience sleep disturbances and often experience daytime tiredness, which in turn may impact on their daytime functioning and academic attainment, but there are few longitudinal data.

Methods: Data on sleep habits and behavior were taken on the same day as an in-hospital polysomnography. This study assesses the developmental sleep profiles of children and young adults aged 4-23 years old with SCA. We examined retrospective polysomnography (PSG) and questionnaire data.

Results: A total of 256 children with a median age of 10.67 years (130 male) were recruited and 179 returned for PSG 1.80-6.72 years later. Later bedtimes and a decrease in total sleep time (TST) were observed. Sleep disturbances, e.g., parasomnias and night waking, were highest in preschool children and young adults at their first visit. Participants with lower sleep quality, more movement during the night and increased night waking experienced daytime sleepiness, are potentially an indicator of lower daytime functioning. Factors influencing sleep quantity included age, hydroxyurea prescription, mean overnight oxygen saturation, sleep onset latency, periodic limb movement, socioeconomic status and night waking.

Conclusion: Sleep serves an important role for daytime functioning in SCA; hence, quantitative (i.e., PSG for clinical symptoms, e.g., sleep-disordered breathing, nocturnal limb movement) and qualitative (i.e., questionnaires for habitual sleep behavior) assessments of sleep should be mutually considered to guide interventions.

Keywords: blood disorders; developmental trajectory; obstructive sleep apnea; polysomnography; sickle cell anaemia; sleep characteristics.

Annual Academy of Sickle Cell and Thalassaemia (ASCAT) Conference: A Summary of the Proceedings

BMC Proc. 2020 Dec 16;14(Suppl 20):21. doi: 10.1186/s12919-020-00204-1.
Authors Crawford Strunk, Andrew Campbell, Raffaella Colombatti, Biree Andemariam, Rachel Kesse-Adu, Marsha Treadwell, Baba P D Inusa

Abstract

The fourteenth annual ASCAT conference was held 21-23 October 2019. The theme of the conference was ‘Sickle Cell and Thalassemia disorders new treatment horizon; while ensuring patient safety and delivering excellence in routine patient care.’ Over the three-day conference, topics on current and novel models of care, advances in bone marrow transplant and gene therapy, as well as the psychosocial aspects of mind, body and health related quality of life were discussed. In addition, blood transfusion, apheresis, iron chelation therapy and acute haemolytic complications were presented. Quality standards in the diagnosis and treatment of sickle cell and thalassemia were reviewed. Experts from Europe, the United Kingdom, the Middle East, the United States and Africa reported up-to-date scientific data, guides to comprehensive care, and current research into developing cures and advancing current therapy were described. In addition, oral and poster presentations on novel research from all over the world were shown during the conference.

Keywords: ASCAT conference; Anaemia; Blood transfusion; Bone marrow transplantation; Sickle cell disease; Thalassemia.

Education, Clinical, Research Sources:

Cleveland Clinic

Ohio Department of Health

Center for Disease Control

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