Sickle Cell News January 2021

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MARAC Advisory Statement: COVID-19 Vaccines

December 14, 2020 — News is evolving rapidly about COVID-19 and COVID-19 vaccines.Early results from the COVID-19 vaccine trials are very promising, although the true benefits and risks will not be known until a larger number of people receive the vaccine. The Centers for Disease Control and Prevention (CDC) lists sickle cell disease (SCD) as one of the populations vulnerable to severe COVID-19. Sickle cell disease raises the risk for serious problems with COVID-19, especially when compared to the same age in the general population. Based on current information, MARAC recommends that people with sickle cell disease receive COVID-19 vaccination. Learn about the side effects, read the FAQs and more in our full statement.
Up to three winners (student teams) will be selected.  1st Prize is $25,000  –  2nd Prize is $15,000  –  3rd Prize is $10,000 
Sickle cell disease (SCD), a group of inherited red blood cell disorders, affects 100,000 Americans, according to the CDC. It can cause severe, chronic pain and other serious problems such as infection, acute chest syndrome, and stroke. Many people do not know about the disease and its complications, and this can contribute to social stigma, a lack of understanding about how SCD affects patients and their families, and less than optimal are for those living with it. Through the Hope for Sickle Cell Disease Challenge the National Heart, Lung, and Blood Institute (NHLBI), part of the National Institutes of Health, seeks to improve awareness about SCD and address the associated myths and stigmas. This Challenge encourages college and graduate students to develop innovative information dissemination tools, instruments, or devices that help spread evidence-based information about SCD, so that people living with the disease can live better, healthier lives. The deadline for Student Team registration is 11:59 p.m. EST on February 26, 2021 and Student Team registration is required. The submission period ends at 11:59 p.m. EST on March 26, 2021. More information about this Challenge, including a link to the full text of the Challenge Announcement, is available on the NHLBI website.  
Groundbreaking SCD Content Presented at the 62nd ASH Annual Meeting and Exposition   The American Society of Hematology (ASH) held its first all-virtual 62nd Annual Meeting & Exposition in early December. The meeting featured 300+ abstracts related to sickle cell disease (SCD) and several sessions with SCD experts on topics such as ‘omics in SCD, pain management and chronic transfusion support. Abstracts presented on groundbreaking CRISPR/Cas9 gene-editing program sparked interest among attendees and the media. Read more about this revolutionary technology presented at ASH’s Annual Meeting in the Wall Street Journal and Associated Press.  Media also took interest in ASH’s report “New Studies Call Attention to Effects of Structural Inequities on Health in America” and the inherent impact this has on SCD care. The article was underscored by several presentations on, and plentiful media coverage of, COVID-19’s impact on the SCD community, as summarized in MedPage Today’s piece, “Sickle Cell Disease Tied to Worse COVID-19 Outcomes.” An overview of several of these programs and studies will be published in easy to understand language in a future SCDC Update.
Improving Outcomes for Women & Girls: Directory of Clinics and Services for Women and Girls with SCD   The Foundation for Women & Girls with Blood Disorders has created the first searchable online database of clinics dedicated to multi-disciplinary care for females with sickle cell disease (SCD). The Women and Girls with Sickle Cell Disease (WGSCD) Directory provides comprehensive information on the services for women/girls with SCD, many at the 140 federally funded Hemophilia Treatment Centers (HTCs) in the United States. Most HTCs offer a multidisciplinary, comprehensive care model where females are able to see all of the doctors and specialists they need, including a hematologist, nurse practitioners, registered nurses, genetic counselors, physical therapists and social workers; in addition, these clinics have providers with specialized expertise in SCD or trait.
National Alliance of Sickle Cell Centers (NASCC) Launched   Despite the trials of 2020, it has been a year of promise for sickle cell disease (SCD), with efforts to improve access to quality SCD care.  To build on these efforts, the National Alliance of Sickle Cell Centers (NASCC) was launched. The NASCC is a (pending) 501(c)(3) corporation that has the goals to: Provide LEADERSHIP in defining, implementing, monitoring, and evaluating sickle cell centersImprove AWARENESS AND EDUCATION of SCD PROMOTE equitable access to care and therapeutics for individuals living with SCDAdvance QUALITY IMPROVEMENT and QUALITY ASSURANCE for comprehensive sickle cell centers  Foster active COLLABORATION with other organizations that share similar goals.   The NASCC looks forward to collaborating with the SCD community and partners in the service of these goals.  The NASCC Officers include: President:            Julie Kanter, MD, The University of Alabama at BirminghamVice President:    Sophie Lanzkron, MD, Johns Hopkins School of MedicineTreasurer             Deepa Manwani, MD, Montefiore Medical CenterSecretary:            Marsha Treadwell, PhD, UCS Benioff Children’s Hospital Oakland More information about the inaugural NASCC recognized comprehensive sickle cell centers and the application process for center recognition will be released soon.  Please contact Dr. Julie Kanter jkanter@uabmc.edu with questions.
ASH Recognizes U.S. Assistant Secretary for Health ADM Brett Giroir with 2020 Outstanding Service Award   The American Society of Hematology’s (ASH) recently honored ADM Brett Giroir, MD, Assistant Secretary for Health at the U.S. Department of Health and Human Services (HHS), with the 2020 ASH Outstanding Service Award for his support of hematology research and patient care.  ASH’s 2020 President Stephanie Lee, MD, MPH, of Fred Hutchinson Cancer Research Center noted “ADM Giroir has been a trusted partner and advocate, bringing much needed attention to sickle cell disease, and ensuring that progress in conquering this disease in the United States and across the globe is a top priority for the federal government.”  Read the press release about the award here and watch ADM Giroir’s acceptance speech here.
Co-Pay Relief Program Expanded to Include COVID-19 Payments   The Patient Advocacy Foundation recently broadened their ongoing efforts to support individuals living with sickle cell disease navigate complex disability systems and overcome insurance coverage and financial burdens by expanding their Co-Pay Relief program to include coverage of COVID-19 expenses. The Co-Pay Relief program may provide direct payment for co-payments, co-insurance and deductibles required by a person’s insurance for medications prescribed to treat and manage their disease. The program helps patients on a first-come, first-serve basis and processes applicants in the order in which their completed applications are received. The maximum annual award for a single patient’s COVID-9 care is $500. Click here to learn more about the eligibility criteria. 

Interested patients, providers, and pharmacies may apply for assistance by calling the Co-Pay Relief team toll-free at 866-512-3861, or by visiting https://copays.org/.
2020 ASH Advocacy Efforts

In 2020, the American Society of Hematology (ASH) continued to work with federal agencies, leaders at the United States Department of Health and Human Services (HHS) and the U.S. Congress to help enhance and expand government activities in sickle cell disease (SCD) research, training, and services.  As part of these efforts, in November, ASH and over 60 SCD partner groups sent a letter to Congressional leaders asking for $5 million of dedicated funding for the SCD Data Collection Program be included in the final House-Senate negotiated omnibus appropriations bill for fiscal year (FY) 2021.  Additionally, ASH has been working with SCD champions on Capitol Hill to introduce legislation that would authorize the Centers for Medicare & Medicaid Services (CMS) to develop a Medicaid demonstration project to improve access to state-of-the-art, high quality outpatient care for individuals living with SCD with a focus on young adults.  See other highlights of ASH’s related efforts over the past year.

Watch Six-Part Animated Video Series: Blood Transfusions: What You Need to Know and Do.

A red blood cell transfusion is a common procedure that is usually safe; however, this procedure can sometimes cause health problems, such as infections and iron overload (a buildup of excess iron in the body). Watch the six-part animated video series produced by the Georgia Health Policy Center and the Sickle Cell Community Consortium about what you can do to lower your risk of health problems related to blood transfusions:

SCD and COVID-19 Resources 

 The following links are frequently updated with timely information for the community and providers.

1st Patients To Get CRISPR Gene-Editing Treatment Continue To Thrive https://www.npr.org/sections/health-shots/2020/12/15/944184405/1st-patients-to-get-crispr-gene-editing-treatment-continue-to-thrive

NPR has had exclusive access to follow Gray through her experience since she underwent the landmark treatment on July 2, 2019. Since the last time NPR checked in with Gray in June, she has continued to improve. Researchers have become increasingly confident that the approach is safe, working for her and will continue to work. Moreover, they are becoming far more encouraged that her case is far from a fluke.

At a recent meeting of the American Society for Hematology, researchers reported the latest results from the first 10 patients treated via the technique in a research study, including Gray, two other sickle cell patients and seven patients with a related blood disorder, beta thalassemia. The patients now have been followed for between three and 18 months.

All the patients appear to have responded well. The only side effects have been from the intense chemotherapy they’ve had to undergo before getting the billions of edited cells infused into their bodies.

The New England Journal of Medicine published online this month the first peer-reviewed research paper from the study, focusing on Gray and the first beta thalassemia patient who was treated.

Study Identifies Potential Trends in Pediatric Sickle Cell Mortality https://www.hcplive.com/view/study-identifies-potential-trends-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).

The 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,” weas published in Blood.

Articles in the medical literature

1.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. Online ahead of print.
Authors James B Papizan  1 , Shaina N Porter  1 , Akshay Sharma, Shondra M Pruett-Miller  1
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. Full-text links    
2.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. Online ahead of print.
Authors Stephanie O Ibemere  1 , Sarah B Dubbs  2 , Huiman X Barnhart  3 , Jacqueline L Brown  4 , Caroline E Freiermuth  5 , Patricia Kavanagh  6 , Judith A Paice  7 , John J Strouse  8 , R Gentry Wilkerson  9 , Paula Tanabe  10 , 
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.
3.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. Online ahead of print.
Authors Joanne Harmon  1 , Victoria Pitt  2 , Peter Summons  3 , Kerry J Inder  4
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. Full-text links    
4.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 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. Full-text links    
5.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. Full-text links    
6.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 behaviour 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, 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 behaviour) assessments of sleep should be mutually considered to guide interventions.
Keywords: blood disorders; developmental trajectory; obstructive sleep apnoea; polysomnography; sickle cell anaemia; sleep characteristics. Full-text links      
7. 
8.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  1 , Andrew Campbell  2 , Raffaella Colombatti  3 , Biree Andemariam  4 , Rachel Kesse-Adu  5 , Marsha Treadwell  6 , Baba P D Inusa  7
Abstract The fourteenth annual ASCAT conference was held 21-23 October 2019. The theme of the conference was ‘Sickle Cell and Thalassaemia 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 thalassaemia 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; Thalassaemia. Conflict of interest statement A Campbell: research funding and consultancy from Global Blood Therapeutics (GBT), Novartis; and consultancy for Bluebird Bio; B Andemariam: consultancy for Bluebird Bio, CRISPR/Vertex, Novartis, NovoNordisk, Roche, Cyclerion, Terumo, Sanofi; DSMB: Global Blood Therapeutics; research funding: Imara; B Inusa: education funding: Novartis, AstraZeneca, Global Blood Therapeutics, Celgene, Vertex; ARISE declaration: This project has received funding from the European Union Horizon 2020 Research and Innovation Programme under Marie-Sklowdowska Curie Agreement, No 824021 ARISE project C. Strunk: consultancy Global Blood Therapeutics, Novartis and Medunik USA and Forma Therapeutics; R Colombatti: research funding: Global Blood Therapeutics, Novartis. No disclosures to declare from the other co-authors. 4 references Full-text links      
9.Hemoglobin Target and Transfusion Modality for Adult Patients With Sickle Cell Disease Acute Chest Syndrome J Intensive Care Med. 2020 Dec 14;885066620978770. doi: 10.1177/0885066620978770. Online ahead of print.
Authors Joseph L Simonson  1 , Juliana A Rosentsveyg  1 , Noah G Schwartz  2 , Abhinav Agrawal  1 , Seth Koenig  3 , Gulrukh Z Zaidi  1 Abstract
Background: Despite the importance of transfusion in treating sickle cell disease acute chest syndrome, the target hemoglobin and optimal modality for transfusion remain unknown.
Objectives: To compare hospital length of stay (LOS) in intensive care unit (ICU) patients with acute chest syndrome transfused to hemoglobin ≥ 8 g/dL versus patients transfused to hemoglobin < 8 g/dL; and to compare hospital LOS in acute chest syndrome patients treated with and without exchange transfusion.
Methods: We performed a retrospective cohort study of all acute chest syndrome patients treated in the medical ICU at 2 tertiary care hospitals between January 2011 and August 2016 (n = 82). We compared median hospital LOS in patients transfused to hemoglobin ≥ 8 g/dL by the time of ICU transfer to the medical floor versus patients transfused to hemoglobin < 8 g/dL as well as patients who received exchange transfusion versus no exchange transfusion using Wilcoxon rank-sum tests. We modeled the association between hospital LOS and hemoglobin at ICU transfer to the medical floor using multivariable log-linear regression.
Results: Median hospital LOS was about half as long for patients transfused to hemoglobin ≥ 8 g/dL versus hemoglobin < 8 g/dL (8.0 versus 16.5 days, P = 0.008). There was no difference in LOS for patients treated with and without exchange transfusion. On average, a 1 g/dL increase in hemoglobin was associated with a 19.5% decrease (95% CI 10.8-28.2%) in LOS, controlling for possible confounding factors.
Conclusions: Transfusion to a hemoglobin target ≥ 8 g/dL is associated with decreased hospital LOS in patients with acute chest syndrome. There was no difference in LOS between patients who received exchange transfusion and those who did not.
Keywords: acute chest syndrome; blood transfusion; exchange transfusion; sickle cell anemia. Full-text links    
10.Post-Transcriptional Genetic Silencing of BCL11A to Treat Sickle Cell Disease N Engl J Med. 2020 Dec 5. doi: 10.1056/NEJMoa2029392. Online ahead of print.
Authors Erica B Esrick  1 , Leslie E Lehmann  1 , Alessandra Biffi  1 , Maureen Achebe  1 , Christian Brendel  1 , Marioara F Ciuculescu  1 , Heather Daley  1 , Brenda MacKinnon  1 , Emily Morris  1 , Amy Federico  1 , Daniela Abriss  1 , Kari Boardman  1 , Radia Khelladi  1 , Kit Shaw  1 , Helene Negre  1 , Olivier Negre  1 , Sarah Nikiforow  1 , Jerome Ritz  1 , Sung-Yun Pai  1 , Wendy B London  1 , Colleen Dansereau  1 , Matthew M Heeney  1 , Myriam Armant  1 , John P Manis  1 , David A Williams  1
Abstract Background: Sickle cell disease is characterized by hemolytic anemia, pain, and progressive organ damage. A high level of erythrocyte fetal hemoglobin (HbF) comprising α- and γ-globins may ameliorate these manifestations by mitigating sickle hemoglobin polymerization and erythrocyte sickling. BCL11A is a repressor of γ-globin expression and HbF production in adult erythrocytes. Its down-regulation is a promising therapeutic strategy for induction of HbF.
Methods: We enrolled patients with sickle cell disease in a single-center, open-label pilot study. The investigational therapy involved infusion of autologous CD34+ cells transduced with the BCH-BB694 lentiviral vector, which encodes a short hairpin RNA (shRNA) targeting BCL11A mRNA embedded in a microRNA (shmiR), allowing erythroid lineage-specific knockdown. Patients were assessed for primary end points of engraftment and safety and for hematologic and clinical responses to treatment.
Results: As of October 2020, six patients had been followed for at least 6 months after receiving BCH-BB694 gene therapy; median follow-up was 18 months (range, 7 to 29). All patients had engraftment, and adverse events were consistent with effects of the preparative chemotherapy. All the patients who could be fully evaluated achieved robust and stable HbF induction (percentage HbF/(F+S) at most recent follow-up, 20.4 to 41.5%), with HbF broadly distributed in red cells (F-cells 58.9 to 93.6% of untransfused red cells) and HbF per F-cell of 9.0 to 18.6 pg per cell. Clinical manifestations of sickle cell disease were reduced or absent during the follow-up period.
Conclusions: This study validates BCL11A inhibition as an effective target for HbF induction and provides preliminary evidence that shmiR-based gene knockdown offers a favorable risk-benefit profile in sickle cell disease. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT03282656). Copyright © 2020 Massachusetts Medical Society. Cited by 1 article Full-text links    
11.CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia N Engl J Med. 2020 Dec 5. doi: 10.1056/NEJMoa2031054. Online ahead of print.
Authors Haydar Frangoul  1 , David Altshuler  1 , M Domenica Cappellini  1 , Yi-Shan Chen  1 , Jennifer Domm  1 , Brenda K Eustace  1 , Juergen Foell  1 , Josu de la Fuente  1 , Stephan Grupp  1 , Rupert Handgretinger  1 , Tony W Ho  1 , Antonis Kattamis  1 , Andrew Kernytsky  1 , Julie Lekstrom-Himes  1 , Amanda M Li  1 , Franco Locatelli  1 , Markus Y Mapara  1 , Mariane de Montalembert  1 , Damiano Rondelli  1 , Akshay Sharma  1 , Sujit Sheth  1 , Sandeep Soni  1 , Martin H Steinberg  1 , Donna Wall  1 , Angela Yen  1 , Selim Corbacioglu  1
Abstract Transfusion-dependent β-thalassemia (TDT) and sickle cell disease (SCD) are severe monogenic diseases with severe and potentially life-threatening manifestations. BCL11A is a transcription factor that represses γ-globin expression and fetal hemoglobin in erythroid cells. We performed electroporation of CD34+ hematopoietic stem and progenitor cells obtained from healthy donors, with CRISPR-Cas9 targeting the BCL11A erythroid-specific enhancer. Approximately 80% of the alleles at this locus were modified, with no evidence of off-target editing. After undergoing myeloablation, two patients – one with TDT and the other with SCD – received autologous CD34+ cells edited with CRISPR-Cas9 targeting the same BCL11A enhancer. More than a year later, both patients had high levels of allelic editing in bone marrow and blood, increases in fetal hemoglobin that were distributed pancellularly, transfusion independence, and (in the patient with SCD) elimination of vaso-occlusive episodes. (Funded by CRISPR Therapeutics and Vertex Pharmaceuticals; ClinicalTrials.gov numbers, NCT03655678 for CLIMB THAL-111 and NCT03745287 for CLIMB SCD-121.). Copyright © 2020 Massachusetts Medical Society. Cited by 2 articles Full-text links    
12.Educational needs of patients and caregivers living with sickle cell disease results in development of web-based patient decision aid J Adv Nurs. 2020 Dec 4. doi: 10.1111/jan.14704. Online ahead of print. Authors Diana Ross  1   2   3 , Cynthia Sinha  2   3 , Nitya Bakshi  1   2   3 , Lakshmanan Krishnamurti  1   2   3
Abstract Aims: We performed an assessment to understand perceived decisional needs among those living with sickle cell disease. Additionally, we desired understanding of their preferred methods and quality of learning and sought guidance in development of a web-based patient decision aid.
Design: The purpose of this qualitative study was to determine ways patients and caregivers receive education about sickle cell disease and available therapies. We sought to understand preferences for education, quality of current knowledge and information they would like to obtain.
Methods: Recruitment for the initial needs assessment occurred between October 2013 -April 2014. Further recruitment for clarification of internet-based searches occurred between January 2015 -September 2016. We conducted a total of 201 semi-structured qualitative interviews with patients and caregivers.
Results: Six themes emerged: healthcare provider education is good but does not meet all the learning needs of the patient/caregiver; patients/caregivers feel a strong desire to seek information about treatment options on their own; adult patients and parents diverged in their core objectives in seeking information: quality of life (QOL) was the major outcome of interest in considering potential treatment options; experience of peers is preferred source for learning about treatment options; and educational needs may be supplemented with a web-based interactive educational tool. Conclusion: Patients with sickle cell disease and their caregivers are motivated by a desire to improve QOL in seeking treatment options and use many methods to seek education to supplement what they learn from their healthcare providers and may benefit from the use of a web-based decision aid. Impact Educational needs of patients/caregivers with sickle cell disease were identified and provide the basis to inform the design of educational strategies for them. Nurses and others can assist with learning needs by sharing the website and answering questions that arise.
Keywords: education; haematology; nurses; nursing sickle cell disease; qualitative. © 2020 John Wiley & Sons Ltd. 27 references Full-text links    
13.Neuropathic pain in sickle cell disease: measurement and management Hematology Am Soc Hematol Educ Program. 2020 Dec 4;2020(1):553-561. doi: 10.1182/hematology.2020000142.
Authors Alexander Glaros  1   2 , Amanda M Brandow  3
Abstract The identification of chronic pain and neuropathic pain as common contributors to the overall pain experience of patients with sickle cell disease (SCD) has altered the way we should evaluate difficult-to-treat pain. The recognition of these 2 entities is not generally routine among various medical specialties and provider levels that treat SCD. Due to the relative recency with which neuropathic pain was first described in SCD, validated assessment tools and evidence-based treatments remain lacking. Although clinical assessment and judgment must continue to inform all decision making in this understudied area of SCD pain management, a number of validated neuropathic pain assessment tools exist that can make possible a standardized evaluation process. Similarly, investigation of available neuropathic pain treatments for the uniquely complex pain phenotypes of SCD has only just begun and is better established in pain conditions other than SCD. The aim of this review is to briefly summarize the proposed basic pathophysiology, assessment, and treatment of neuropathic pain in patients with SCD. Furthermore, the aim of this review is to encourage an expanded framework for the assessment and treatment of SCD pain that appreciates the hidden complexities of this common complication of SCD. © 2020 by The American Society of Hematology. Conflict of interest statement Conflict-of-interest disclosure: The authors declare no competing financial interests. 4 figures Full-text links      
14.Optimizing the management of chronic pain in sickle cell disease Hematology Am Soc Hematol Educ Program. 2020 Dec 4;2020(1):562-569. doi: 10.1182/hematology.2020000143.
Authors Ifeyinwa Osunkwo  1 , Hazel F O’Connor  1 , Elna Saah  2 Abstract Chronic pain in sickle cell disease (SCD) refers to pain present on most days lasting over six months. It can start during childhood and the prevalence increases with age. By adulthood, over 55% of patients experience pain on over 50% of days; 29% reporting pain on 95% of days. The true prevalence of chronic pain in SCD is likely underappreciated as it is mostly managed at home. Patients with chronic pain and SCD frequently seek acute care for exacerbation of underlying chronic pain difficult to distinguish from their usual acute vaso-occlusive crises. When treating chronic pain in SCD, the challenge is distinguishing between non-SCD related etiologies versus chronic pain resulting from SCD pathophysiological processes. This distinction is important to delineate as it will drive appropriate management strategies. Chronic pain in SCD has profound consequences for the patient; is often associated with comorbid psychiatric illnesses (depression and anxiety), not dissimilar from other chronic pain syndromes. They may also experience challenges with sleep hygiene, various somatic symptoms, and chronic fatigue that impair quality of life. How best to treat chronic pain in SCD is not definitively established. Both acute and chronic pain in SCD is typically treated with opioids. Emerging data suggests that chronic opioid therapy (COT) is a suboptimal treatment strategy for chronic pain. This review will discuss the complexity of managing chronic pain in SCD; pain that may be dependent or independent of the underlying SCD diagnosis. We will also describe alternative treatment approaches to high-dose COT. © 2020 by The American Society of Hematology. 5 figures Full-text links      
15.Social aspects of chronic transfusions: addressing social determinants of health, health literacy, and quality of life Hematology Am Soc Hematol Educ Program. 2020 Dec 4;2020(1):175-183. doi: 10.1182/hematology.2020000104.
Author Jennifer Webb  1
Abstract Chronic monthly transfusions are a lifesaving preventative therapy for many patients with sickle cell disease; however, the burden of this therapy for patients and families is high. In the United States, there is overlap in the population affected by sickle cell disease and those with the greatest burden of social needs. Hematology providers caring for patients with SCD have an opportunity to screen for and mitigate social determinants of health, especially in those receiving chronic transfusion therapy given the frequent interactions with the healthcare system and increased demand on already potentially limited resources. Given the complexity of the treatment and medication regimens, providers caring for patients receiving chronic transfusions should implement universal strategies to minimize the impact of low health literacy, as this therapy imposes a significant demand on the health literacy skills of a family. Despite the social and literacy burden of this intervention, it is reassuring that quality of life is preserved as patients with SCD on chronic transfusion therapy often report higher health related quality of life than their peers receiving other disease modifying therapies. © 2020 by The American Society of Hematology. Conflict of interest statement Conflict of interest disclosure: The author has no relevant conflicts of interest. 1 figure Full-text links      
16.Considerations for Cannabis Use to Treat Pain in Sickle Cell Disease J Clin Med. 2020 Dec 1;9(12):3902. doi: 10.3390/jcm9123902.
Authors Donovan A Argueta  1 , Anupam Aich  1 , Fjolla Muqolli  1 , Hemanth Cherukury  1 , Varun Sagi  2 , Nicholas V DiPatrizio  3 , Kalpna Gupta  1   4
Abstract Pain in Sickle Cell Disease (SCD) is a major comorbidity and unique with acute pain due to recurrent and episodic vaso-occlusive crises as well as chronic pain, which can span an individual’s entire life. Opioids are the mainstay treatment for pain in SCD. Due to recent health crises raised by adverse effects including deaths from opioid use, pain management in SCD is adversely affected. Cannabis and its products are most widely used for pain in multiple conditions and also by patients with SCD on their own. With the availability of “Medical Cannabis” and approval to use cannabis as medicine across majority of States in the United States as well as over-the-counter preparations, cannabis products are being used increasingly for SCD. The reliability of many of these products remains questionable, which poses a major health risk to the vulnerable individuals seeking pain relief. Therefore, this review provides up to date insights into available categories of cannabis-based treatment strategies, their mechanism of action and pre-clinical and clinical outcomes in SCD. It provides evidence for the benefits and risks of cannabis use in SCD and cautions about the unreliable and unvalidated products that may be adulterated with life-threatening non-cannabis compounds.
Keywords: cannabinoid; cannabis; pain; sickle cell disease; vaso-occlusive crises. Conflict of interest statement KG reports grants from Grifols, Cyclerion and 1910 Genetics, and honorarium from Novartis, Tautona Group, and CSL Behring, outside the submitted work. 146 references 1 figure Full-text links      
17.Preventive measures for the critical post-exercise period in sickle cell trait and disease J Appl Physiol (1985). 2020 Dec 3. doi: 10.1152/japplphysiol.00855.2020. Online ahead of print.
Authors Laurent André Messonnier  1 , Pablo Bartolucci  2 , Thomas d’Humières  3 , Etienne Dalmais  4 , Jean-René Lacour  5 , Hubert Freund  4 , Frédéric Galactéros  6 , Leonard Féasson  7
Abstract The immediate post-exercise/physical activity period is critical for sickle cell trait (SCT) carriers and disease (SCD) patients. Indeed, exercise-related blood acidosis known to trigger the cascade: HbS deoxygenation and polymerization, and subsequently red blood cells sickling, aggravates during the initial post-exercise period. This deterioration lies on the conjunction of two facts: First, blood lactate and H+ concentrations continue to increase during several minutes after exercise completion, aggravating blood acidosis. Second, blood lactate concentrations remain elevated and pH altered for 20-45 minutes in case of inactivity after intense exercise, keeping acid/base balance disturbed for a long period post-exercise. Therefore, the risk of complications (including vaso-occlusive crises and even sudden deaths) persists and even worsens several minutes after intensive exercise completion in SCT carriers or SCD patients. Light physical activity following intense exercise (namely active recovery) may, by accelerating lactate removal and acid/base balance restoration, be of paramount importance in that context. Scientific evidences suggest that a light exercise below or at maximum to the first lactate threshold would constitute an appropriate strategy.
Keywords: active recovery; anemia; complications; high-intensity exercise; vaso-occlusive crisis. Full-text links    
18.Impact of sickle cell disease on patients’ daily lives, symptoms reported, and disease management strategies: Results from the international Sickle Cell World Assessment Survey (SWAY) Am J Hematol. 2020 Dec 2. doi: 10.1002/ajh.26063. Online ahead of print. Authors Ifeyinwa Ify Osunkwo  1 , Biree Andemariam  2 , Baba P D Inusa  3 , Fuad El Rassi  4 , Beverley Francis-Gibson  5 , Alecia Nero  6 , Caterina P Minniti  7 , Cassandra Trimnell  8 , Miguel R Abboud  9 , Jean-Benoît Arlet  10 , Raffaella Colombatti  11 , Mariane de Montalembert  12 , Suman Jain  13 , Wasil Jastaniah  14 , Erfan Nur  15 , Marimilia Pita  16 , Laurie DeBonnett  17 , Nicholas Ramscar  18 , Tom Bailey  19 , Olivera Rajkovic-Hooley  19 , John James  20
Abstract Sickle cell disease (SCD) is a genetic disorder, characterized by hemolytic anemia and vaso-occlusive crises (VOCs). Data on the global SCD impact on quality of life (QoL) from the patient viewpoint are limited. The international Sickle Cell World Assessment Survey (SWAY) aimed to provide insights into patient-reported impact of SCD on QoL. This cross-sectional survey of SCD patients enrolled by healthcare professionals and advocacy groups assessed disease impact on daily life, education and work, symptoms, treatment goals, and disease management. Opinions were captured using a Likert scale of 1-7 for some questions; 5-7 indicated ‘high severity/impact’. 2145 patients (mean age 24.7 years [standard deviation (SD) = 13.1], 39% ≤18 years, 52% female) were surveyed from 16 countries (six geographical regions). A substantial proportion of patients reported that SCD caused a high negative impact on emotions (60%) and school achievement (51%) and a reduction in work hours (53%). A mean of 5.3 VOCs (SD = 6.8) was reported over the 12 months prior to survey (median 3.0 [interquartile range 2.0-6.0]); 24% were managed at home and 76% required healthcare services. Other than VOCs, fatigue was the most commonly reported symptom in the month before survey (65%), graded ‘high severity’ by 67% of patients. 39% and 38% of patients reported depression and anxiety, respectively. The most common patient treatment goal was improving QoL (55%). SCD confers a significant burden on patients, epitomized by the high impact on patients’ QoL and emotional wellbeing, and the high prevalence of self-reported VOCs and other symptoms. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved. Full-text links  

Meetings for the Sickle Cell Community

SCDAA Webinar on National Academies SCD Report The Sickle Cell Disease Association of America (SCDAA) will be hosting a webinar on the National Academies of Sciences, Engineering, and Medicine (NASEM) Report: Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action (2020) on Thursday, December 17 from 2:30-3:30 p.m. ET, with guest speaker Dr. Kim Smith-Whitley from the Children’s Hospital of Philadelphia. The target audience for this presentation is people living with sickle cell disease and their caregivers. Those interested in attending should email lwilson@sicklecelldisease.org.
Register to Attend a Free Symposium on SCD: What’s New with Transplant and Gene Therapy? The Doris Duke Charitable Foundation  and St. Jude Children’s Research Hospital are co-hosting a virtual symposium entitled Sickle Cell Disease (SCD): What’s New with Transplant and Gene Therapy? The symposium is targeted for SCD researchers and health care providers and will focus on understanding new technologies related to hematopoietic stem cell transplantation and gene therapy. This free symposium will be held Tuesday, March 2, 2021 from 7:30 a.m. to 3:00 p.m. CT. Please note, the program is free, but pre-registration is required by March 1, 2021.  Register now.
Save the Date and Register for IASCNAPA Sickle Cell Conference

The International Association of Sickle Cell Nurses and Professional Associates (IASCNAPA) Sickle Cell Conference is going virtual! The conference will focus on multi-dimensional care, with a theme of Treating the Whole Person. The dates have changed to April 14 and 15, 2021.  The target audience is nurses, advanced practice providers, social workers, and other non-physician healthcare providers. The IASCNAPA Sickle Cell Nursing Curriculum will be presented during the conference. This curriculum is specific for inpatient nurses who provide care to people living with sickle cell disease. Look out for registration information coming soon at www.iascnapa.org.
    Register for the 2021 Virtual Hemoglobinopathy Counselor Training Course

The 2021 Hemoglobinopathy Counselor Training Course, will be presented virtually by Cincinnati Comprehensive Sickle Cell Center, on April 14 and 15.  The training course will use lectures and discussion to prepare clinicians and hemoglobinopathy counseling professionals to work effectively with patients with hemoglobinopathies by increasing their knowledge of hemoglobin disorders and variants. The registration fee is $250 and nursing and social work continuing education credits will be available. For more information, please email: SCDEvents@cchmc.org. Register here by April 1, 2021.  Registration is available online at www.cincinnatichildrens.org/HemoglobinopathyCTC