Sickle Cell Research Articles

Hydroxyurea reduces the levels of the fetal globin gene repressors ZBTB7A/LRF and BCL11A in erythroid cells in vitro

Abstract Objectives Hydroxyurea (HU) is the most widely used therapy for adults and children with sickle cell disease (SCD). It is believed to act largely by inducing the transcription of fetal γ-globin genes to generate fetal hemoglobin (HbF), which inhibits the pathological polymerization of sickle hemoglobin (HbS). The mechanisms by which hydroxyurea elevates HbF are unclear. We explored the hypothesis that hydroxyurea induces HbF expression by inhibiting the expression of 2 γ-globin gene repressors, BCL11A and ZBTB7A (also known as LRF), which normally bind the γ-globin gene promoters to inhibit their expression after birth. Methods We treated immortalized murine erythroleukemia cells and normal human donor CD34+ hematopoietic stem and progenitor cell-derived erythroblasts with hydroxyurea and measured the effects on globin, BCL11A and ZBTB7A protein and mRNA expression. Results Treating murine erythroleukemia cells or human CD34+ hematopoietic stem and progenitor cell-derived erythroblasts with hydroxyurea reduced the protein levels of BCL11A and ZBTB7A compared to the vehicle-treated control. BCL11A mRNA levels were reduced in both cell types upon hydroxyurea treatment. However, ZBTB7A mRNA levels were only reduced in human CD34+ hematopoietic stem and progenitor cell-derived erythroblasts. Conclusions Hydroxyurea can act in erythroid cells to reduce the levels and activity of two direct fetal γ-globin transcriptional repressors with accompanying de-repression of the γ-globin genes and induction of HbF, which may explain the mechanism of action leading to amelioration of symptoms in SCD patients treated with this drug.

Sickle cell disease awareness and perception among Christian religious leaders in Accra Metropolis: a qualitative study.

Sickle Cell Disease (SCD) is a severe hemoglobin gene mutation disorder inherited from both parents. 2% of Ghanaian newborns are affected by SCD; one in three Ghanaians has the hemoglobin S gene. Christian religious leaders may play a role in the prevention of SCD through the promotion of genetic counseling, genotype screening for premarital couples, and offering counseling to couples on prenatal screening and diagnosis for SCD. However, little is known about the awareness and perception of SCD among Christian religious leaders in Ghana, and this study aims to explore these. This study adopted a qualitative descriptive design to explore the awareness and perception of SCD among Christian religious leaders in the capital city of Ghana. A purposive sampling technique selected 16 participants from churches under the main Christian groups. The participants were chosen based on their roles and responsibilities within their respective churches. Data was collected using a semi-structured interview guide, which included open-ended questions to encourage participants to share their thoughts and experiences. The interviews were conducted in a private setting to ensure confidentiality. The data was then analyzed using a thematic analysis approach, which involved identifying recurring themes and patterns in the participants' responses. The study's findings are crucial. They reveal a high awareness of SCD among Christian religious leaders, but also some misconceptions. Most of the religious leaders knew SCD was a genetic disease, although a few associated SCD with superstitious beliefs, poor dietary intake, and lifestyle. Some also stated that SCD was a disease of the blood group instead of the defective haemoglobin gene. They perceived SCD to be burdensome, disruptive, and draining, and they associated the disease with burnout in Persons Living with SCD (PLWSCD) and their families. The religious leaders had a good social network with PLWSCD, including family, friends, colleagues, and congregants. These findings underscore the need for intense education about SCD, especially among Christian religious leaders. It is crucial to engage all stakeholders to intensify public awareness and education about SCD while improving the management and social support systems available to PLWSCD and families. This includes the religious institution's leadership, PLWSCD and families, the Ministry of Health, Ghana Health Service, and the Ghana Education Service. As active stakeholders, religious leaders can play a vital role in supporting PLWSCD if they are equipped with the necessary knowledge about the condition. .

A-354 Evaluating Emergent POC Technology for Sickle Cell Testing in Resource Limited Settings

Abstract Background Sickle cell disease (SCD) represents a collection of inherited hematological disorders characterized by abnormal sickle-shaped erythrocytes resulting in an increased risk of morbidity and mortality. SCD represents a significant global health burden, affecting more than 300,000 newborns per year. Most of these births occur in resource limited areas, including sub-Saharan Africa, where the mortality rate before the age of five is estimated to be as high as 50-80% and the existing infrastructure and resources cannot support most current and robust methods that offer hemoglobin variant detection and quantification for the diagnosis and monitoring of SCD. While newborn screening programs (NBS) to identify individuals affected with SCD have demonstrated efficacy in reducing morbidity and early mortality, NBS programs are limited outside of the US and Europe and face many practical challenges for universal implementation in a resource limited setting. The need for inexpensive and reliable hemoglobin variant detection and quantification at the Point of Care is essential to the diagnosis and management of SCD in resource limited settings with a high prevalence of SCD, and the expansion of NBS programs. This study aims to evaluate an inexpensive testing strategy using two methodologies for POC screening and confirmation of SCD that could be supported in a low resource setting. Methods The two-step testing strategy for evaluation of POC testing for hemoglobin variant detection and quantification included testing residual specimens from normal and known sickle cell patients by first screening with the HemoTypeSC, a qualitative lateral flow immunoassay (LFIA) that has improved sensitivity and specificity from other available LFIA methodologies given the use of monoclonal antibodies for the detection of hemoglobin variants. Confirmatory testing and quantification of hemoglobin variants was accomplished with the use of the Gazelle POC test a miniaturized chip-based cellulose acetate electrophoresis device capable of identification and quantification of normal and variant hemoglobin. Statistical evaluation of device performance and clinical agreement between the device and known disease status was achieved in EP evaluator. Results The two-tier testing strategy demonstrated effective and inexpensive mechanism for SCD screening and confirmation. Overall, the HemoTypeSC and Gazelle demonstrated 100% qualitative agreement between methods, with the total cost of the two-tiered testing strategy estimated at under $6 per sample. Conclusions In conclusion, the two-tiered approach using the HemoTypeSC and Gazelle yielded a practical and cost-effective strategy for screening and confirmation of hemoglobin variants for the detection and monitoring of SCD. Both the strip and chip-based methodologies provide rapid results, are accessible at the point-of-care, and require minimal sample volume, a feature ideal for use in a pediatric population in low resource settings. Overall, these methods show promise for the use and expansion of NBS programs to improve public health initiatives for the diagnosis of SCD.

Glucose-6-phosphate dehydrogenase deficiency detection using fluorocytometric assay: Evaluation after 1 year of clinical implementation.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common enzymopathy that affects red blood cells (RBCs) and renders them susceptible to oxidative stress. G6PD deficiency can cause hemolytic anemia, especially after exposure to certain drugs or infections. The diagnosis of G6PD deficiency is usually based on spectrophotometric measurement of enzyme activity, but this method has limitations in heterozygous females and in patients with other hematological disorders. In this study, we evaluated the use of flow cytometry as an alternative method for detecting G6PD deficiency in 514 samples (265 females and 249 males) from a clinical laboratory. We compared the results of flow cytometry with those of spectrophotometry and molecular analysis, and assessed the performance of flow cytometry in different subgroups of patients. We found that flow cytometry was able to identify G6PD deficiency in most cases, with high sensitivity and specificity. Flow cytometry also allowed the quantification of the percentage of G6PD-deficient RBCs, which varied among heterozygous females due to X-chromosome inactivation. Moreover, flow cytometry detected several cases of G6PD deficiency that were missed by spectrophotometry, especially in heterozygous females with normal or subnormal enzyme activity. However, flow cytometry also showed some false negative results, mainly in patients with sickle cell disease. Therefore, flow cytometry is a reliable and efficient tool for screening G6PD deficiency, but some precautions should be taken in interpreting the results in patients with other hematological conditions.

Getting Help During Active Pain Crises in Sickle Cell Disease: Patient and Caregiver Perspectives in Canada

Plain Language Summary What is this summary about? This is a plain language summary of an article originally published in Patient Preference and Adherence. This study aimed to identify the notable symptoms and impacts of sickle cell disease from the point of view of individuals living with sickle cell disease and their caregivers. The study also sought to understand the factors involved in individuals living with sickle cell disease’ and caregivers’ decisions and preferences if and when they seek care during a pain crisis. This summary describes: the symptoms experienced by adolescents and adults living with sickle cell disease and their severity; the treatments they and their caregivers prefer to use when they are experiencing a pain crisis; and the factors that go into deciding when and whether individuals living with sickle cell disease and their caregivers should seek outside help -- to go to a hospital, for example - during a pain crisis. What were the results? Individuals living with sickle cell disease undergoing an acute pain crisis and their caregivers consider many factors when deciding whether to seek care at a medical facility. These include: The intensity of their symptoms If the facility has a treatment plan for them already in place If the facility has long wait times If the facility has an understanding and compassionate staff The individual's age and ability to manage their daily responsibilities Racial bias, shown in the actions and lack of empathy of Emergency Department staff toward individuals living with sickle cell disease, frequently factored into the individuals' and caregivers’ decision-making and hinders their ability to get the treatment needed during a pain crisis. What do the results mean? There is a need for a unified care team at medical facilities that treats all individuals living with sickle cell disease with the same high level of empathy and treatment quality and for a strong support system for individuals living with sickle cell disease outside of the hospital or clinic. This is an abstract of the Plain Language Summary of Publication article. View the full Plain Language Summary PDF of this article to read the full-text Link to original article here

Sickle Cell Disease and Lead Poisoning in New York City, 2005-2019.

Previous analyses of New York City (NYC) health department's lead registry indicated that, among children with lead poisoning, an increased prevalence of sickle cell disease (SCD) exists. However, SCD is not considered a risk factor for lead poisoning. We assessed the association between SCD and childhood lead poisoning to determine if specific lead poisoning prevention efforts are needed for children with SCD. We analyzed NYC's lead registry data for children with venous blood lead levels (BLLs) ≥15 mcg/dL during 2005 to 2019. t tests and χ2 tests were performed to compare demographic characteristics, BLLs, and lead exposure risks in non-Hispanic Black children with and without SCD. A t test was used to compare observed SCD prevalence among Black children with BLLs ≥15 mcg/dL with an estimated 0.43% SCD prevalence among Black NYC children. Among 1728 Black children with BLLs ≥15 mcg/dL identified, 37 (2.14%) had SCD. When comparing children with and without SCD, both mean age at peak BLL (62.8 versus 42.7 months; P = .003) and peak BLL (42.59 versus 23.06 mcg/dL; P = .008) were higher for children with SCD. Among risk factors for lead exposure, children with SCD had higher prevalence of pica. Observed SCD prevalence was 1.71% higher than estimated SCD prevalence among Black NYC children (P < .001). We found a potential association between SCD and childhood lead poisoning. Pica emerged as a potentially important risk factor. Our findings might have implications for lead poisoning prevention guidelines for children with SCD.

Seroprevalence of SARS-CoV-2 in pediatric hematology-oncology patients.

The COVID-19 pandemic disproportionately affected persons with underlying medical conditions. SARS-CoV-2 infection susceptibility and vaccine effectiveness in pediatric hematology-oncology patients were unknown. From February to July 2022, anti-spike and anti-nucleocapsid Ig were assayed in 354 pediatric hematology-oncology subjects, including 53 oncology patients receiving chemotherapy (cancer), 150 patients with sickle cell disease (SCD), and 151 benign consult and long-term follow-up patients (controls). Participants completed a questionnaire. Frequencies of COVID-19 infection, defined by positive PCR/antigen test or anti-nucleocapsid Ig, were 62% in cancer, 71% in SCD, 52% in controls, with SCD statistically different than controls (p=.001). Infection was associated with COVID-19 exposure, Hispanic/Latino or Black/African American ethnicity, multi-family dwelling, sports participation; COVID-19 booster decreased association with infection. In COVID-19-positive cancer patients, 58% had positive anti-nucleocapsid and 76% had positive anti-spike (≥10U/mL), compared to essentially 100% seroconversion in SCD and controls (p<.0001, p=.01, respectively). Infection led to high anti-spike (≥2500U/mL) in 12% cancer, 14% SCD, and 15% controls (p=.93). Vaccination resulted in anti-spike positivity in 90% cancer, 100% SCD, and 100% controls (p=.06), and in high anti-spike in 20% cancer, 47% SCD, and 41% controls (p=.36). Of boosted subjects, one of two cancer, 6/6 SCD, and 19/19 controls exhibited high anti-spike. Cancer patients demonstrated similar SARS-CoV-2 infection frequency as controls, but diminished antibody response to infection and vaccination. SCD patients exhibited seroconversion indistinguishable from controls. Vaccination was associated with higher frequency of high anti-spike than infection; vaccination plus booster was most effective in eliciting high anti-spike antibody detectable beyond 90days.

Microbiome in sickle cell disease: Pathophysiology and therapeutic insights.

Sickle cell disease (SCD) is a complex genetic blood disorder characterized by abnormal haemoglobin, resulting in sickle-shaped red blood cells. While extensive research has concentrated on the genetic and physiological aspects of SCD, recent studies suggest a potential role of the human microbiome in SCD pathophysiology, adding new dimensions to its understanding. This review synthesizes current knowledge on the microbiome's involvement in SCD, focusing on alterations in the gut microbiome composition and diversity compared to healthy individuals, and their implications for disease pathogenesis. We explore how microbiome changes may contribute to vaso-occlusive crises and other complications, along with the possible associations of specific microbial taxa or markers with disease crises and clinical outcomes. Additionally, we discuss the potential of microbiome-targeted interventions, including probiotics, dietary modifications, and faecal microbiota transplantation, in managing SCD complications and improving patient outcomes. Understanding the intricate relationship between the microbiome and SCD could lead to innovative therapeutic strategies and personalized interventions for better managing the disease. This review underscores the importance of further microbiome research and its integration into holistic SCD care.

Understanding exercise (in)tolerance in sickle cell disease: impacts of hemolysis and exercise training on skeletal muscle oxygen delivery.

Sickle cell disease (SCD) is characterized by central (cardiac) and peripheral vascular dysfunctions, significantly diminishing exercise capacity and quality of life. Although central cardiopulmonary abnormalities in SCD are known to reduce exercise capacity and quality of life; the impact of hemolysis and subsequent cell-free hemoglobin (Hb)-mediated peripheral vascular abnormalities on those outcomes are not fully understood. Despite the recognized benefits of exercise training for cardiovascular health and clinical management in chronic diseases like heart failure, there remains substantial debate on the advisability of regular physical activity for patients with SCD. This is primarily due to concerns that prolonged and/or high-intensity exercise might trigger metabolic shifts leading to vaso-occlusive crises. As a result, exercise recommendations for patients with SCD are often vague or nonexistent, reflecting a gap in knowledge about the mechanisms of exercise intolerance and the impact of exercise training on SCD-related health issues. This mini-review sheds light on recent developments in understanding how SCD affects exercise tolerance, with a special focus on the roles of hemolysis and the release of cell-free hemoglobin in altering cardiovascular and skeletal muscle function. Also highlighted here is the emerging research on the therapeutic effects and safety of exercise training in patients with SCD. In addition, the review identifies future research opportunities to fill existing gaps in our understanding of exercise (in)tolerance in SCD.

Health-related quality of life of children and adolescents with sickle cell disease: An evolutionary concept analysis

The concept of Health-Related Quality of life (HRQOL) of children and adolescents with Sickle cell disease (SCD) is not clearly understood due to the lack of available studies. This review aimed to elucidate various attributes and related concepts of HRQOL in children and adolescents with SCD using Rodgers' (2000) concept analysis framework. A systematic search was performed to identify studies reporting the attributes, antecedents, consequences, surrogate terms, and related concepts of HRQOL in children and adolescents with SCD. The review included 75 articles, including 70 quantitative, two mixed-methods, and three qualitative studies. These were categorized into attributes, antecedents, consequences, surrogate terms, related concepts, and an exemplar of HRQOL in children and adolescents with SCD. The review identified nine important attributes. It includes multidimensional and dynamic concepts, acknowledging the illness, maintaining emotional balance and self-control, coping with the disease, pain management, stigma and discrimination, treatment burden, palliative care and personal resilience. The antecedents were knowledge and attitude toward the disease, self-efficacy, social support, spirituality and spiritual well-being, disease severity, access to healthcare, environmental factors, and financial considerations. The consequences were independence in personal life, improved physical health outcomes, psychological well-being, family and caregiver well-being, improved family, social and peer relationships and social interactions, improved school performance, and improved overall HRQOL and long-term outcomes. This analysis provides an overview of HRQOL concepts related to children and adolescents with SCD, guiding further research into nursing care and clinical practice.

Perinatal risk factors and neurocognitive outcomes in children and adolescents with sickle cell disease.

The literature on cognitive and academic outcomes for children with sickle cell disease (SCD) who experience perinatal risk factors is limited. We aimed to evaluate if low birthweight (LBW), gestational age, and history of neonatal intensive care unit (NICU) admission were associated with neurocognitive functioning, grade retention, or receipt of early intervention or formal educational support in children with SCD. This prospective birth cohort study included 336 participants, ages 8-18, with SCD, who received cognitive testing as part of standard of care and whose caregivers completed behavioral rating scales. Multivariable generalized linear regression models were used to examine associations between perinatal risks and outcome variables, after adjusting for demographic and medical covariates. The prevalence of NICU admission and LBW were 12.03% and 13.50%, respectively. Lower birthweight, earlier gestational age, and NICU admission were associated with worse working memory performance and receipt of early intervention services. Lower birthweight and NICU admission were also associated with slower processing speed. History of NICU admission was associated with caregiver ratings of hyperactivity and emotional dysregulation. The effects of perinatal risk factors on neurocognitive, academic, or educational outcomes were not dependent on SCD genotype. History of LBW or NICU admission was associated with worse cognitive outcomes and increased use of early intervention services among children with SCD. Early identification of perinatal risk factors will help identify children who will benefit from formal developmental or neuropsychological evaluations to manage the comorbidity of SCD and perinatal risks and facilitate increased intervention.

Impact of Etonogestrel-releasing contraceptive implant use in cisgender women with Sickle cell disease

BackgroundSickle cell disease is a hereditary hemolytic anemia that exposes women to increased health risks especially in pregnancy, with serious implications for the woman and fetus. Acute pain episodes can occur multiple times per month and result in reduction of quality of life and disruption of her life. ObjectiveTo assess the clinical, including pain and metabolic parameters of women with sickle cell disease using etonogestrel-releasing contraceptive implants. MethodsWomen with sickle cell disease, aged 18–40 years, with reports of pain crises in the preceding 3 months were included and followed up for 12 months. Blood samples were collected to evaluate the blood count, reticulocytes, liver profile (alkaline phosphatase, gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, and total bilirubin and its fractions), lipid profile, and lactate dehydrogenase levels before and 6 and 12 months after implant insertion. The following clinical variables were analyzed every 3 months: bleeding pattern, blood pressure, weight, body mass index, pain intensity (assessed using a visual analogic scale (VAS) from 0 to 10), and frequency of pain crises. ResultsTwenty-three women completed the study. There were no differences in laboratory variables between baseline and 6 and 12 months after implant insertion. Similarly, clinical variables did not differ, except for pain intensity (VAS pre-insertion = 8 vs. VAS 12 months post insertion = 4; p = 0.005) and frequency of pain crises (pre-insertion = 6 vs. 12 days/month post insertion = 0; p = 0.000). ConclusionsEtonogestrel-releasing contraceptive implants were associated with a reduction in the intensity and frequency of pain crises in women with sickle cell disease. Moreover, it was safety among these population due to no changes in laboratory parameters during the first 12 months of use.

Potassium dynamics in sickle cell anemia: clinical implications and pathophysiological insights

Potassium dynamics are critical in the pathophysiology of sickle cell anemia (SCA), a genetic disorder characterized by the presence of abnormally shaped red blood cells that lead to various complications such as vaso-occlusive crises and hemolytic anemia. This review focuses on the clinical implications and pathophysiological insights of potassium regulation in SCA, highlighting its impact on disease progression and potential therapeutic strategies. The dysregulation of potassium transport in SCA leads to significant K+ efflux and cellular dehydration, exacerbating the sickling process. Dehydrated sickle cells, due to potassium loss, become more rigid and prone to causing blockages in small blood vessels, leading to painful vaso-occlusive crises and ischemia. Furthermore, chronic hemolysis in SCA, aggravated by potassium imbalance, contributes to severe anemia and systemic complications. These insights underscore the importance of maintaining potassium homeostasis to mitigate disease severity and improve patient outcomes. Therapeutic strategies targeting potassium regulation show promise in managing SCA. Inhibitors of the Gardos channel, such as senicapoc, have demonstrated potential in reducing sickling and hemolysis. Additionally, hydration therapy plays a crucial role in maintaining electrolyte balance and preventing RBC dehydration. A comprehensive approach that includes monitoring and correcting electrolyte imbalances, along with standard treatments like hydroxyurea and blood transfusions, is essential for effective disease management.

Targeting ICAM1 to Ameliorate Vaso-Occlusion and Inflammation in Sickle Cell Disease.

Sickle cell disease (SCD) is a hereditary disorder characterized by vaso-occlusion, inflammation, and tissue damage. Intercellular adhesion molecule 1 (ICAM-1) plays a crucial role in the pathophysiology of SCD by promoting the adhesion of sickle cells to the endothelium, contributing to vaso-occlusion and tissue damage. The ICAM-1 gene encodes a glycoprotein that interacts with lymphocyte function-associated antigen 1 (LFA-1) and macrophage 1-antigen (Mac-1) receptors, perpetuating inflammation, and oxidative stress. The NF-κB signaling pathway regulates ICAM-1 expression, which is elevated in patients with SCD, leading to increased endothelial cell activation and damage. Targeting ICAM-1 and its interactions with sickle cells and the endothelium has emerged as a potential therapeutic strategy for managing SCD. This review highlights the complex interplay between ICAM-1, sickle cells, and the endothelium, and discusses the potential of ICAM-1-targeted therapies for mitigating VOC and improving the quality of life for patients with SCD.

Introducing a G-Makassar variant in HSCs by in vivo base editing treats sickle cell disease in mice

Precise repair of the pathogenic mutation in hematopoietic stem cells (HSCs) represents an ideal cure for patients with sickle cell disease (SCD). Here, we demonstrated correction of the SCD phenotype by converting the sickle mutation codon (GTG) into a benign G-Makassar variant (GCG) using in vivo base editing in HSCs. We demonstrated successful production of helper-dependent adenoviral vectors expressing an all-in-one base editor mapping to the sickle mutation site. In HSC-enriched cells from SCD patients, transduction with the base editing vector in vitro resulted in 35% GTG > GCG conversion and phenotypic improvements of derived red blood cells. After ex vivo transduction of HSCs from a SCD mouse model and subsequent transplantation, we achieved an average of 88% editing at the target site in transplanted mice. Importantly, in vivo HSC base editing followed by selection generated 24.5% Makassar variant in long-term repopulating HSCs of SCD mice. The treated animals demonstrated correction of disease hallmarks without showing noticeable side effects. Off-target analyses at top-scored genomic sites revealed no off-target editing. This in vivo approach requires only one non-integrating vector, only intravenous/subcutaneous injections, and minimal in vivo selection. This technically simple approach has the potential for scalable applications in resource-limiting regions where SCD is prevalent.

The use of abstract animations and a graphical body image for assessing pain outcomes among adults with sickle cell disease

Painimation, a novel digital pain assessment tool, allows patients to communicate their pain quality, intensity, and location using abstract animations and a paintable body image. This study determined the construct validity of pain animations and body image measures by testing correlations with validated pain outcomes in adults with sickle cell disease (SCD). Analyses used baseline data from a multisite randomized trial of 359 adults with SCD and chronic pain. Participants completed questionnaires on demographics, pain severity, frequency and interference, catastrophizing, opioid use, mood and quality of life, plus the Painimation app. Participants were categorized by selected pain animations, and were split into groups based on the proportion of painted body image. The “shooting” pain animation and greater body image scores associated with poorer pain outcomes in univariate analyses, except “happy” mood days. Potential confounding was evaluated by age, gender, race, education, disability, site, depression, and anxiety. Only depression scores significantly covaried in multivariate models, accounting for the effect of greater body image score and shooting animation on all outcomes except daily pain intensity. Both pain animations and body image measures correlated with validated pain outcomes, quality of life and mental health measures. This demonstrates animations and body image data can assess SCD pain severity, potentially with more accuracy than a 0-10 scale. In exploratory analyses, depression scores accounted for the association between Painimation and other pain outcomes. Future research will explore whether Painimation can differentiate biological and psychosocial pain components. PerspectiveThis article presents the preliminary construct validity of Painimation in sickle cell disease (SCD) by examining the associations of “pain animations” and body area image data with daily e-diary and traditional self-report pain outcomes.

Examining community-level social vulnerability and emergency department use for people living with sickle cell disease in Michigan.

This study examined associations between emergency department (ED) visits and social vulnerability index (SVI) among Michigan's population with sickle cell disease (SCD) using data from the Michigan Sickle Cell Data Collection program (n=3658 in 2018). SVI was higher among census tracts where people with SCD resided (mean SVI=0.67; SD=0.27) compared to census tracts without SCD residents (mean SVI=0.39; SD=0.25; p<.001). For children with SCD, for every 0.1 increase in SVI score, the number of ED visits increased by 6% (IRR=1.061; SE=0.03; p=.038). Future research should investigate the association between SVI and ED use, at the community and household levels, to elucidate strategies to reduce ED use among children with SCD.

CRISPR/Cas9 in the treatment of sickle cell disease (SCD) and its comparison with traditional treatment approaches: a review.

Sickle cell disease (SCD) is a common hereditary blood disorder that profoundly impacts individuals' health, causing chronic pain, anemia, organ damage, increased susceptibility to infections, and social and psychological effects. Over the years, advances in treatment have improved the long-term outcomes of SCD patients. However, problems such as limited access to hematopoietic stem cell transplantation (HSCT) and potential complications associated with the available therapies underscore the importance of continued research and development. The recent FDA approval of Casgevy (Exagamglogene autotemcel), a genetic therapy based on CRISPR/Cas9 technology, demonstrates a comprehensive effort to address the complexity of SCD using new technologies. This review explores the potential of CRISPR/Cas9 for treating SCD and evaluates its efficacy, safety, and long-term outcomes compared to traditional treatment approaches. Long-term research is needed to comprehensively assess the safety, effectiveness, and inclusion of CRISPR/Cas9, ensuring its overall efficacy.

Optical Coherence Tomography Angiography of Macular Microangiopathy in Children With Sickle Cell Disease.

In this study, we identified the presence of sickle cell maculopathy and determined correlations between hemolysis indicators and systemic and ocular manifestations in children with sickle cell disease (SCD). Thirty-three patients with SCD 5 to 18 years of age underwent optical coherence tomography angiography (OCTA) as part of a thorough eye examination. The hematological indices and clinical data (hemoglobin, fetal hemoglobin, mean corpuscular volume, and frequency of sickle cell-associated complications and therapy) were collected. The SCD group contained 33 patients (66 eyes), and the control group contained 36 healthy participants (72 eyes). The SCD group had significantly thinner parafoveal thickness ( P =0.041) and significantly smaller parafoveal volume ( P =0.041) than the controls. The SCD group had lower deep capillary plexus density than the controls ( P =0.029). The SCD group had significantly smaller flow areas than the controls ( P <0.001). The foveal avascular zone (FAZ) perimeter, foveal density, and FAZ area in the entire retina did not differ significantly between the groups ( P >0.05). The platelet level was negatively correlated with parafoveal and perifoveal thickness and density. OCTA detected early macular microvascular changes in children and adolescents with asymptomatic SCD.

Impact of Vitamin D Supplementation on Pain Management in Sickle Cell Disease Patients

Background: Vitamin D deficiency is prevalent among patients with sickle cell disease, regardless of their age or the season. Since there has been no extensive research on the impact of vitamin D on pain in sickle cell disease, this study aimed to evaluate how vitamin D supplementation influences pain management in these patients. Materials and Methods: This retrospective study was conducted on children (12.3±4.45 years old) with definitive diagnosis of sickle cell. The study was done in the Department of Oncology of Shahid Sadoughi Hospital, Yazd, Iran, over the years 2019-2021. Thirty patients (14 boys and 16 girls) with vitamin D insufficiency and deficiency entered the study and 50000 IU vitamin D was given weekly for 16 weeks. The measurement of vitamin 25(OH) D3 before and after intervention was done by ELISA method (Monobind kit, USA). Pain intensity assessment was also done. Other relevant data were extracted from the patients’ medical records. Results: In this study, amomg 30 patients, 46.6% of them had vitamin D deficiency. A significant reduction in pain intensity was observed in patients following the intervention (p&lt;0.05). Conclusion: Based on the findings of this study, vitamin D was effective in reducing pain intensity in these patients. Therefore, vitamin D can be used in the pain management of these patients.