Sickle Cell Research Articles

5176 Time In Range Preferred Over A1c And Fructosamine To Monitor Glycemic Control In Sickle Cell Disease

Abstract Disclosure: A. Patel: None. B. Simon: None. Introduction: In sickle cell disease, hemoglobin A1c is unreliable due to anemia, hemolysis, transfusions, and increased red blood cell turnover. In this population, plasma glucose should be used to make a diagnosis of diabetes, but there are no reliable long-term measures of glycemic control. Measures of serum protein glycation such as fructosamine are often used as markers of short-term control[1]. Continuous glucose monitoring (CGM) time in range (TIR) may offer another more reliable metric of control in this population2. Case: A 58-year-old male presented to the office for uncontrolled type 2 diabetes mellitus. His medical history included sickle cell anemia (Hb SS disease), hypertension, monoclonal gammopathy, and priapism. He was diagnosed with type 2 diabetes mellitus approximately one year prior based on a fructosamine level of 470 umol/L (0-285 umol/L) and elevated fasting glucose level of 128 mg/dL. He started metformin 500 mg daily. Three months later, repeat fructosamine was 401 umol/L, and metformin was increased. Months later, fructosamine levels remained elevated at 419 umol/L; metformin was increased to 2 grams daily and he was referred to endocrinology. The patient was given a CGM (Freestyle Libre 2 system, Abbott Diabetes Care) as an additional method to assess control. CGM showed an excellent 2-week TIR (70-180mg/ dL) of 98%. Repeat fructosamine after 2 weeks of CGM wear was elevated at 500 umol/L. It was hypothesized that the history of IgG kappa monoclonal gammopathy was falsely elevating his fructosamine level. A glycated albumin level was 13.5% (10.7-13.5%). The patient was advised to discontinue his metformin. Four months later, his glycated albumin remained in range, and a 2-week TIR was 100%. Discussion: This case demonstrates how sickle cell disease and monoclonal gammopathy affect laboratory values typically used to diagnose and monitor type 2 diabetes. Fructosamine, a measure of non-enzymatic glycation of serum proteins, is non-specific2. Increased protein from monoclonal gammopathy (giving more protein glycation sites) was the probable cause of the persistently elevated fructosamine, leading to overtreatment of what may not have been a true diagnosis of diabetes. This case also demonstrates the value of CGM, with glucose values and TIR indicating near normoglycemia. Diagnostic CGM may be a useful measure of glucose control in patients with hemoglobinopathies.

8291 Graves’ Disease and Moyamoya Syndrome: A Complex Case of Thyroid Dysfunction and Neurovascular Abnormalities

Abstract Disclosure: A. Jamil: None. Q.V. Luong: None. A. Llorens Bonilla: None. A. Siddiqui: None. Background: Moyamoya disease is a cerebrovascular disease characterized by progressive stenosis and occlusion of cerebral arteries, particularly the internal carotid arteries, proximal anterior and middle cerebral arteries associated with a net-like collateral vessel formation. Moyamoya disease in association with certain systemic conditions (e.g. Graves’ disease, sickle cell anemia, neurofibromatosis type 1, and Down Syndrome) has been referred to as moyamoya syndrome. Graves’ disease is an autoimmune disease in which the development of thyroid-stimulating hormone (TSH) receptor autoantibodies leads to overproduction of thyroid hormones. Although the pathophysiology is unclear, Graves’ disease can adversely impact the clinical course of moyamoya syndrome.Clinical Case: A 26-year-old woman diagnosed with Graves’ disease at the age of 20 years who was in remission presented to the ED with right upper extremity weakness and headache. A stroke work-up was performed, and an initial CT head without contrast showed an acute infarct in the left temporal area. Extensive workup for hypercoagulability and cardiac causes were negative. MRI brain showed multiple infarcts of the left cerebral hemisphere with ivy sign, which are prominent linear or punctate high intensity areas in the subarachnoid space reflecting the development of collaterals that occurs in moyamoya disease. TSH at the time was noted to be <0.01 uIU/mL (range: 0.30-4.20 uIU/mL), indicating a thyrotoxic state. She was discharged on methimazole and antiplatelet therapies. However, the patient continued to have hypertension and headaches which did not resolve with the return to euthyroidism. At age 29, she again developed acute right upper and lower extremity weakness, and consequently presented to the ED. Imaging studies showed multiple punctate infarcts in her bilateral frontal lobes and bilateral ICA stenosis consistent with moyamoya disease. However, her biochemical studies showed euthyroidism. Ultimately, she underwent right frontotemporal craniotomy and direct parietal superficial temporal artery to middle cerebral artery bypass by neurosurgery to decrease her future stroke risk for her moyamoya syndrome, and her Graves’ disease remains in remission.Conclusions: The coexistence of Graves’ disease in moyamoya syndrome may suggest a pathophysiologic connection. It has been suggested that hemodynamic changes in cerebrovascular flow due to thyrotoxicosis might contribute to ischemic neurologic deficits. Surgical intervention for revascularization procedures should be attempted after optimal control of thyrotoxicosis, as this may help to prevent further ischemic events in the future and improve patient outcomes. Presentation: 6/1/2024

8194 Extramedullary Hematopoiesis Involving Bilateral Adrenal Glands In A Patient With Sickle Cell Anemia

Abstract Disclosure: V.T. Pham: None. L.N. Sendos: None. Title: Extramedullary hematopoiesis involving bilateral adrenal glands in a patient with sickle cell anemia Background: Extramedullary hematopoiesis refers to blood cell production occurring outside the bone marrow. It is a reactive process caused by inadequate production or excessive destruction of blood cells typically seen in patients with hereditary anemias or infiltrative bone marrow disorders. Extramedullary hematopoiesis usually occurs in the spleen, liver and lymph nodes, but it can also very rarely arise from the adrenal glands. Case Presentation:We present a case of a 42-year-old male with a history of sickle cell anemia who presented with chest pain and shortness of breath and had a chest CT angiography which incidentally showed a 5.6 x 3.8 cm left adrenal mass and a 2.9 x 2.1 cm right adrenal mass. Further evaluation with an MRI abdomen with and without contrast revealed a 5.5 cm lobulated left adrenal mass with patchy areas of microscopic fat and faint delayed heterogeneous enhancement as well as a 2.2 cm right adrenal nodule. The nodules were described as markedly T2 hypointense with heterogeneous T1 hyperintense/isointense signal on MRI with a broad differential diagnosis including extramedullary hematopoiesis in bilateral adrenal glands, lipid poor adenoma or neoplasm. Regarding his sickle cell disease history, the patient was diagnosed as an infant and had very rare episodes of sickle cell pain crisis as a child. However, once he entered adulthood, he began to have multiple episodes of sickle cell pain crisis requiring hospitalizations and transfusions. On further review of patient’s prior imaging scans during these previous hospitalizations, he was first noted to have bilateral sub centimeter adrenal nodules on a CT Abdomen without contrast done almost a decade prior to his current presentation. We ordered biochemical evaluation which did not show any evidence of adrenal hormonal hypersecretion. His case was discussed at our multidisciplinary conference with the radiology and surgery team and it was concluded that the imaging characteristics were most consistent with extramedullary hematopoiesis in the setting of bilateral adrenal gland involvement and patient’s history of sickle cell anemia. Therefore, no immediate surgical resection was recommended. Given the size of the left adrenal mass being greater than 4 cm in size, we advised follow-up imaging for surveillance. Discussion:There has been a rise in detection of adrenal incidentalomas due to the increased use of advanced diagnostic imaging in healthcare settings. When patients with hematologic diseases are found to have adrenal incidentalomas, it is important to consider extramedullary hematopoiesis in the differential diagnosis to avoid unnecessary invasive procedures and surgeries. Presentation: 6/2/2024

Antisickling, hemolytic activities and toxicological evaluation of three plants species from the Nigerien Pharmacopoeia: Annona senegalensis Linné. Boscia senegalensis (Pers) Lam. and Ampelocissus afr

The aim of this study consits to evaluate the antisickling and antihemolytic activities and to determine the subacute toxicity of three plants Annona senegalensis L.; Boscia senegalensis (Pers) Lam.; and Ampelocissus africana (Lour) Merr.. The plant material contains leaves and bark of Annona senegalensis roots, leaves and bark root of Boscia senegalensis and the roots of Ampelocissus africana. A single method (80% ethanol maceration) is used to extract the five samples. The antisickleemic and antihemolytic effects are established with sickle cells disease (SCD) in the presence of sodium metabisulfite. Subacute toxicity is tested on Wistar strain rats. All samples showed an antisickling effect but leaves of Annona senegalensis (LAS) showed the highest percentage of antisickling activity (89.55%) at 50mg/ml. The anti-hemolytic effect was demonstrated in all samples by inhibition of hemolysis in the presence of a hemolysant. The toxicity results showed that the aqueous extracts of Annona senegalensis leaves and Boscia senegalensis root bark have non-toxic effects to wistar strain rats. However, some manifestations including fatigue, stretching and slight dyspenea were observed at doses of 150mg/mL and 300mg/mL. This work can contribute as a starting point towards the development of an improved traditional medicine (ITM) method which can help to treat the sickle cell disease. Keywords: Annona senegalensis L., Boscia senegalensis (pers) Lam and Ampelocissus Africana (Lour) Merr. Antisickness activity, Toxicity.

Beyond Ischemia: The Rare Occurrence of Hemorrhagic Strokes in Pediatric Sickle Cell Anemia

Beyond Ischemia: The Rare Occurrence of Hemorrhagic Strokes in Pediatric Sickle Cell Anemia

Alloimmunization and consequential delayed hemolytic transfusion reactions in sickle cell disease patients: A case series

Abstract: Alloimmunization is a significant complication of blood transfusion, especially in sickle cell patients, and may lead to a delayed hemolytic transfusion reaction (DHTR). DHTR is defined as evident hemolysis and a positive direct antiglobulin test (DAT) 24 h to 28 days posttransfusion with either a positive eluate or a newly identified alloantibody in the plasma. Hyperhemolysis syndrome (HS) is a fatal form of DHTR in which the posttransfusion hemoglobin (Hb) level is less than the pretransfusion Hb level. In this case series, we have reported three cases of alloimmunized sickle cell disease patients with clinically significant DHTR. The second case is typical of HS. All three cases were DAT positive, alloimmunized with multiple alloantibodies, and had substantial hemolysis posttransfusion. In this series, we have provided an algorithmic approach to resolve such complex immunohematological problems and have highlighted some of the limitations of serology methods. High-dose corticosteroid and intravenous immunoglobulin prove to be an effective treatment for DHTR.

Prevalence and associated risk factors of myocardial ischemia in children living with sickle cell anemia in Lagos, Nigeria.

Myocardial ischemia (MI) in children living with sickle cell anemia (SCA) is rarely reported. MI among children living with this disease could portend untoward outcomes on their quality of life and survival. This study evaluated the prevalence and associated risk factors of MI in children living with SCA during a vaso-occlusive crisis (VOC) compared with those with SCA who had no symptoms nor an MI in the past (those in "steady state") in Lagos, Nigeria. This comparative cross-sectional study was conducted over 10 months (between March and December 2019) among 250 children living with SCA aged 6 months-18 years (125 in VOC and 125 age and sex-matched controls in steady state). The assessment of MI was determined by measuring cardiac troponin T (cTnT) and electrocardiography (ECG). The prevalence of MI measuring cTnT alone in children with SCA during VOC and steady state was 42.4% and 23.2%, respectively. Comparatively, measuring ECG alone, the prevalence of MI in VOC and steady state was 40.8% and 20.8%, respectively. The prevalence of MI measuring cTnT and ECG in children with SCA in VOC and steady state was 38.4% and 20%, respectively. Older age, severity of pain, longer duration of illness, frequent crises per year, elevated white blood cells, and platelet count were significantly associated with MI in participants with SCA. However, with multivariate analysis, age, severity of pain, and elevated platelet counts remained significantly associated with the occurrence of MI. This study affirms the high prevalence of MI in children with SCA irrespective of the diagnostic criteria. Routine evaluation should be done in this cohort to avert MI-associated sequelae.

Assessment of Biventricular Systolic and Diastolic Function Using Conventional and Strain Echocardiography in Children with Sickle Cell Disease Surviving 1-year After Hematopoietic Stem Cell Transplant.

Hematopoietic stem cell transplant (HSCT) is a potentially curative therapy for children with sickle cell disease (SCD). The effects of HSCT on ventricular function are not well characterized in children with SCD. Echocardiograms from children with SCD who underwent HSCT between 2007 and 2017 were retrospectively analyzed before and 1-year after HSCT. Left ventricular (LV) volumes, mass, and ejection fraction were calculated by the 5/6 area*length method. LV end-diastolic and systolic dimensions, septal, and posterior wall thickness, and fractional shortening were measured by M-mode. Mitral and tricuspid inflow Dopplers (E and A waves) as well as mitral, tricuspid, and septal tissue Dopplers (E', A') were assessed. E/A, E'/A' and E/E' ratios were calculated. Biventricular strain imaging was performed using speckle-tracking echocardiography. Peak global systolic longitudinal and circumferential LV strain, and global longitudinal right ventricular strain, as well as early and late diastolic strain rate, were measured on LV apical 4-chamber, LV short-axis mid-papillary, and RV apical views, respectively. Forty-seven children (9.7 ± 5.5years, 60% male) met inclusion criteria. Pre-HSCT, subjects had mild LV dilation with normal LV systolic function by conventional measure of ejection fraction and fractional shortening. There was a significant reduction in LV volume, mass, and ejection fraction after HSCT, but measurements remained within normal range. LV longitudinal and circumferential strain were normal pre-HSCT and showed no significant change post-HSCT. RV strain decreased after HSCT, but the absolute change was small, and mean values were normal both pre- and post-HSCT. Conventional measures of diastolic function were all normal pre-HSCT. Post-HSCT there was a reduction in select parameters, but all parameters remained within normal range. Early and late diastolic strain rate parameters showed no significant change from pre- to post-HSCT. At one-year after HSCT in children with SCD conventional measures of systolic and diastolic function are within normal limits. Except for a small decrease in RV systolic strain with values remaining within normal limits, systolic strain and diastolic strain rate values did not significantly change 1-year after HSCT.

Metabolic profile characterization of voxelotor in human urine based on in vivo and in vitro models for doping control.

Voxelotor was approved for the treatment of sickle cell anemia as a potent hemoglobin S polymerization inhibitor. Owing to its ability to affect blood components and its potential to enhance athletic performance, voxelotor was included in the prohibited list issued by the World Anti-Doping Agency in 2023, banning its use both in and out of competition. This study aimed to comprehensively investigate the metabolic profile of voxelotor in human urine and identify suitable metabolites for long-term analytical retrospectivity in doping control. A novel strategy for metabolite identification was established by combining in vivo human administration with isotope labeling-based in vitro metabolism analysis. A single microdose of voxelotor was administered orally to five volunteers, and urine samples were collected for up to 28 days post-administration. Concurrently, in vitro incubation of human liver microsomes with voxelotor and D3-voxelotor was conducted, and the microsomal incubates were analyzed via liquid chromatography-high-resolution mass spectrometry. Targeted metabolite searches in human urine samples and automated nontargeted screening of isotope metabolite ion pairs in incubation samples led to the discovery of 9 phase I metabolites and 23 phase II metabolites. Analysis of the urine excretion curves revealed that 4 metabolites, along with voxelotor, were suitable for long-term anti-doping monitoring, with a detection window exceeding 20 days. Using both in vivo and in vitro metabolic models, this study provides comprehensive insight into the metabolic profile of voxelotor in human urine for the first time, enhancing the capacity for doping screening and extending the retrospectivity of voxelotor detection.

Characteristics and outcomes of children and young adults with sickle cell disease supported with extracorporeal membrane oxygenation (ECMO): An updated analysis of the ELSO registry.

Sickle cell disease (SCD) is a global hemoglobinopathy; approximately 300 000 individuals are diagnosed annually. Acute chest syndrome (ACS), a common complication, leads to significant hospitalization and mortality, particularly in cases of severe respiratory distress. ECMO outcomes in this specific population are poorly described. This retrospective observational study, utilizing data from the Extracorporeal Life Support Organization (ELSO) registry, focuses on children and young adults (<40 years) with SCD undergoing ECMO from 1998 to 2022. We observed a growing trend in ECMO cases over the last 15 years, with 210 SCD patients identified in the registry (five neonates, 95 children, 110 adults). ECMO was predominantly initiated for pulmonary support (62%), and most of the primary diagnoses were related to SCD (reported as "SCD" or "acute chest syndrome"). The global survival rate was 55.8% (59% for children and 52.7% for adults). None of the children supported for extracorporeal cardiopulmonary resuscitation survived, and only 2/18 (11%) of adults cannulated for ECPR survived. Complication rates, including acute renal failure (33.8%) neurological events (13%), thrombotic (23.3%), or bleeding events (22.9%) were not noticeably different from reported outcomes in the ELSO registry. Our findings suggest that ECMO outcomes in SCD patients align with general ECMO trends and may not be limited by suspected unfavorable results in children and young adults. Despite limitations, our study contributes valuable insights into using ECMO in SCD, emphasizing the need for further research and understanding in this underexplored domain.

Newborn Screening for Sickle Cell Disease in Catalonia between 2015 and 2022-Epidemiology and Impact on Clinical Events.

In 2015, Catalonia introduced sickle cell disease (SCD) screening in its newborn screening (NBS) program along with standard-of-care treatments like penicillin, hydroxyurea, and anti-pneumococcal vaccination. Few studies have assessed the clinical impact of introducing NBS programs on SCD patients. We analyzed the incidence of SCD and related hemoglobinopathies in Catalonia and the change in clinical events occurring after introducing NBS. Screening 506,996 newborns from 2015 to 2022, we conducted a retrospective multicenter study including 100 screened (SG) and 95 unscreened (UG) SCD patients and analyzed SCD-related clinical events over the first six years of life. We diagnosed 160 cases of SCD, with an incidence of 1 in 3169 newborns. The SG had a significantly lower median age at diagnosis (0.1 y vs. 1.68 y, p < 0.0001), and initiated penicillin prophylaxis (0.12 y vs. 1.86 y, p < 0.0001) and hydroxyurea treatment earlier (1.42 y vs. 4.5 y, p < 0.0001). The SG experienced fewer median SCD-related clinical events (vaso-occlusive crisis, acute chest syndrome, infections of probable bacterial origin, acute anemia requiring transfusion, acute splenic sequestration, and pathological transcranial Doppler echography) per year of follow-up (0.19 vs. 0.77, p < 0.0001), a reduced number of annual emergency department visits (0.37 vs. 0.76, p < 0.0001), and fewer hospitalizations (0.33 vs. 0.72, p < 0.0001). SCD screening in Catalonia's NBS program has effectively reduced morbidity and improved affected children's quality of life.

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.

Screening for Pulmonary Hypertension in Pregnant Women with Sickle Cell Disease in Sub-Saharan Africa

BackgroundSickle cell disease (SCD) has evolved from a condition predominantly fatal in childhood to a chronic illness impacting many adults, including women of reproductive age. For females with SCD, pregnancy represents one of the greatest health threats, exacerbating existing health challenges and introducing new risks. Despite advancements in healthcare, routine screening for existing complications like pulmonary hypertension (PH) remains inconsistent, particularly in low- and middle-income countries (LMICs), where the prevalence of SCD is highest. Objective(s)This study aimed to assess the feasibility of screening for pulmonary hypertension (PH) in pregnant women with sickle cell disease (SCD) in LMICs, with the goal of enhancing maternal health outcomes in this vulnerable population. Study DesignA prospective multi-centre feasibility study was conducted from September 2022 to February 2023 at teaching hospitals in Ghana and Nigeria. The study included pregnant women with SCD between 28 and 34 weeks of gestation. Screening for PH utilized a tricuspid regurgitation velocity (TRV) criterion (>2.5 m/s), with adherence to American Society of Echocardiography guidelines. Statistical analysis included descriptive statistics and proportions. ResultsAmong 3091 pregnant women attending antenatal care, 88 had SCD (2.8%), and 55 were eligible for the study. We recruited 44 participants (mean age 28.9 years, SD 4.8), with 48% (21/44) SS genotype and 52% (23/44) SC genotype. Most participants (95.3%) had normal TRV (<2.5 m/s), with only one showing elevated TRV, successfully referred. Protocol adherence was 100%. Antenatal outcomes showed 95% echo uptake and 95.7% retention to term whilst postnatal echo follow-up was 43.5%. Notably, 27.1% (10/37) of deliveries required NICU admission, and 18.2% were preterm. The sole participant with PH required ICU care and experienced a preterm delivery with neonatal death on day five. Conclusion(s)Screening and referral for PH in pregnant women with SCD in LMICs are feasible but face challenges in early diagnosis, healthcare personnel availability, and postnatal follow-up. Strategic planning is crucial to address these challenges and improve outcomes in this high-risk population

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.