SS Sickle Cell Disease Research Articles

Detection of Subclinical Cardiac Dysfunction in Patients With Sickle Cell Disease Using Speckle-Tracking Echocardiography

Sickle cell disease (SCD) is characterized by chronic anemia and recurrent ischemia-reperfusion episodes, which can lead to high-output heart failure. The impact of SCD on cardiac structure and function remains underinvestigated. We conducted a single-institution retrospective analysis of clinical and echocardiographic data from patients with hemoglobin SS SCD (SCD-SS) between January 2016 and June 2022. Patients with known heart failure, left ventricular (LV) ejection fraction <50%, moderate or severe valvular heart disease, congenital heart disease, established coronary artery disease, diabetes mellitus, hypertension, or coexistent lung disease were excluded. Compared with healthy controls (n = 28), patients with SCD-SS (n = 66) had a significantly higher left atrial (LA) volume index (35.7 vs 23.9 ml/m², p <0.001) and average E/e' (7.4 vs 6.5, p = 0.003) but lower average e' (12.3 vs 13.6 cm/s, p = 0.047) and LA reservoir strain (32.9% vs 42.4%, p <0.001). Patients with SCD-SS had higher LV end-diastolic (132.5 vs 104.1 ml, p <0.001) and LV end-systolic volumes (51.0 vs 43.8 ml, p = 0.017) with reduced LV global longitudinal strain (17.6% vs 20.0%, p <0.001). In addition, patients with SCD-SS showed reduced right ventricular (RV) global longitudinal strain (19.7% vs 22.8%, p <0.001) in the setting of normal RV tricuspid annular plane systolic excursion. Maximal systolic tricuspid regurgitation velocity (231 vs 202 cm/s, p <0.001) and right atrial area (16.6 vs 12.8 cm², p <0.001) were statistically greater in SCD-SS. Hemoglobin and hematocrit negatively correlated with LA volume index, average E/e', LV end-diastolic and LV end-systolic volumes. In conclusion, patients with SCD-SS had notable differences in cardiac chamber size and impaired LV, RV, and LA strain compared with healthy controls. Further investigations are needed to assess the impact of these variables on SCD clinical course and prognosis.

Hospital Prevalence of Sickle Cell Disease in Children Under 5 Years of Age in a Region of the Democratic Republic of Congo

Backgroung: The burden of sickle cell disease in hospitals is less described in both children and adults where there is a lack of universal screening programs. This is more observed in low-income countries and compromises the life expectancy of people with unrecognized major sickle cell disease. The objective of this study was to estimate the more or less concrete burden of sickle cell disease in pediatric hospitals, mainly in children under 5 years of age. Materials &amp; methods: To do this, a cross-sectional and descriptive survey was carried out at the level of the pediatric services of 5 health facilities of the City of Kindu, capital of the province of Maniema in the Democratic Republic of the Congo from December 2, 2019 to October 15, 2020, that to say 10 months. It consisted mainly in the systematic screening of the electrophoretic profile of children under 5 admitted to the said health facilities using a rapid test. Results: The analyzes showed that the hospital prevalence of major sickle cell disease was 12.7%. The mean age of children with major sickle cell anemia was 41 ± 18 months. The median age was 48 months with the extreme ages 2 and 59 months. The 48 to 59 months age group was represented with 56.1% of children with SS sickle cell disease. The prevalence of sickle cell status was significantly associated with age group (p &lt;0.0001). The sex ratio M/F was 1.1. The sickle cell status was independent of the sex of the child. Conclusion: The findings of this study show that the burden of sickle cell disease in pediatric hospitals and mainly in children under 5 years of age is underestimated in the absence of systematic screening. Faced with the delay in the implementation of universal screening in Africa, systematic hospital screening of all children and mainly those under 5 years of age using rapid tests will improve diagnosis and life expectancy of patients with major sickle cell anaemia.

Use of Conventional Transfusion Thresholds Contributes to Ongoing Iron Overload Issues in Patients with Homozygous (SS) Sickle Cell Disease

Introduction: Homozygous sickle cell disease is characterized by chronic anemia which contributes to a clinical course characterized by recurrent pain crisis episodes. These episodes are usually managed with the use of packed red blood cell products. Randomized data is currently available that supports lower transfusion thresholds in non-sickle cell related conditions including but not limited to patients undergoing orthopedic procedures, cardio-vascular interventions and those needing intensive care. Due to lack of similar randomized trials in patients with sickle cell disease, recommendations from other trials are applied to patients with sickle cell diseases as well. However, this has the potential of worsening iron overload states that patients with sickle cell disease usually suffer from. Methods: Patients with homozygous SS sickle cell disease were evaluated with regarding to transfusion support given during hospitalization for vaso-occlusive pain crisis episodes. The hemoglobin threshold that was used for deciding whether or not to give packed red cell transfusion was studied in patients who were previously getting periodic red blood cell exchange procedures for chronic sickle cell related pain. Serum ferritin levels during the period of exchange transfusion support was compared with levels during simple transfusions. 8 patients were selected from the cohort of patients with homozygous sickle cell disease who had been receiving elective packed red blood cell exchanges. Patients with ferritin levels persistently remaining above 1000 ng/ml were then evaluated with regard to transfusion thresholds used for simple transfusion support during hospitalization for pain crisis episodes. Results: Six patients had persistently high ferritin levels. Thresholds for simple transfusion in this group were studied. A total of 30 units of packed red blood cells were found to be transfused over a 6-month period. During this period only one patient required an exchange transfusion session. 2 out of 30 units were given for a Hgb level above 7 g/dl. The majority, representing 24 out of the total 30 pack red blood cell units were given above a Hgb threshold of 6.0 g/dl. Only 4 units were given using a Hgb threshold less than 6 g/dl. Mean ferritin level before and after the period of simple transfusion support was 6097 ng/ml and 6076 ng/ml respectively. Mean Hgb level in while on exchange transfusion was 7.4 g/dl and it was 6.9 g/dl in those receiving a simple transfusion protocol. Conclusions: Transfusion threshold used in patients with homozygous SS sickle cell disease appears to be similar to patients without sickle cell disease. Current practice based on studies including TRICC and TRISS is to keep the Hgb level above 7 g/dl. This has been shown to be safe and in fact even improves patient outcomes. However, in patients with sickle cell disease this may not be appropriate since their baseline Hgb levels are lower to begin with. Also, transfusions don't appear to improve Hgb levels considerably. These patients also tend to have iron overload at baseline which likely will not improve unless all transfusions are limited. Therefore, applying a lower transfusion threshold would be recommended to avoid acute transfusion related issues and long-term iron overload problems in patients with SS disease.

SS Sickle Cell Disease and Severe Malaria in Children Aged 0 to 15 Hospitalized in the Pediatric Department of the Donka CHU National Hospital in Conakry, Republic of Guinea

Introduction: The superposition of distribution maps of HbS and plasmodium falciparum is at the origin of several theories on the relationship between sickle cell disease and malaria. Objective: Determine the sociodemographic aspect and identify the main complications of SS sickle cell disease in children with severe malaria at the Donka Pediatrics Department. Methods: Prospective, descriptive study, lasting 12 months from January 01 to December 31, 2021 including all children from 0-15 years hospitalized whose diagnoses of severe malaria and SS sickle cell anemia were retained during the study period. Results: The frequency was 6.65%, The age group of 5-9 years represented 41.93% with a sex ratio (M/F) = 1.3. Frequency peaks were encountered in June, July and August (36.56%). Consanguineous marriage was found in 65.59%. Fever was present in 100% of our patients followed by osteo-articular pain (93.54%). Malaria severity criteria were represented by prostration with 81.7%, followed by anemia (77.42%), hyperparasitaemia (46.23%), respiratory distress (45.16%) and seizures (34.4%). Complications were dominated by bronchopneumopathy, osteomyelitis, dactylitis and necrosis of the femoral head. The evolution was favorable in 95.70% of cases. Conclusion: The prevalence of sickle cell disease associated with severe malaria remains high in the department with consanguinity often found. Reducing these two pathologies will necessarily involve the use of means of prevention against malaria and premarital examinations.

Glucose-6-Phosphate Dehydrogenase Deficiency: Difficulties in Diagnosis at the Souro Sanou University Hospital, Burkina Faso

Glucose-6-phosphate dehydrogenase deficiency is the most common enzymopathy worldwide. The precise prevalence of G6PD is unknown in Burkina Faso. The objective of the study was to describe the difficulties to diagnose this disease at the Souro Sanou University hospital (CHUSS) in Bobo-Dioulasso. It involved five patients comprising one child with homozygous SS sickle cell disease, one adolescent screened following a family investigation, and three adults including a man and two women. Blood smear stained with May Grunwald Giemsa was performed to look for specific signs of G6PD-deficient red blood cell and brilliant cresyl Blue for Heinz Bodies. A microscope Olympus BX53 equipped with a Camera (XC10) and connected to a computer was used to read blood smears and capture images. Genes sequencing by Sanger method were performed in a specialized laboratory in molecular genetics. For each analysis, the protocol and instructions of the equipment and reagent manufacturer were applied. Of the five patients, three had anemia and only one had hyperreticulocytosis. Two patients had biological signs of hemolysis and one patient had an elevated CRP. Blood smear stained with MGG and cresyl blue showed specific signs of G6PD-deficient red blood cells and Heinz bodies in all patients. Biochemical analysis and molecular typing confirmed G6PD deficiency. The presence of G6PD-deficient red blood cells in the blood smear guides the diagnosis of G6PD deficiency. The diagnosis is biochemical and is based on the combined measurement of G6PD plus pyruvate kinase and/or hexokinase.

Neuropsychological, behavioral, and quality‐of‐life outcomes in children and adolescents with sickle cell disease treated with nonmyeloablative matched sibling donor hematopoietic cell transplantation: A case series

Despite advances in the treatment of sickle cell disease (SCD), cerebrovascular and cognitive insults can have lifelong consequences. Hematopoietic cell transplantation (HCT) is an established curative therapy, and recent studies have demonstrated efficacy with reduced toxicity nonmyeloablative (NMA) regimens, but little is known about neuropsychological outcomes. The objective of this study was to describe neuropsychological, behavioral, and quality-of-life outcomes with medical correlates in children with SCD who received an NMA matched sibling donor (MSD) HCT. Retrospective cohort analysis of nine recipients with hemoglobin SS SCD who underwent MSD HCT using the National Institutes of Health (NIH) NMA protocol. Mean full-scale intellectual functioning (FSIQ) was average pre-HCT (FSIQ= 92.1, SD 9.0; n = 8) and 2years post-HCT (mean FSIQ= 96.6; SD 11.1; N = 9). Neuropsychological functioning was largely average across all cognitive domains, and no pre/post-HCT differences were found to be statistically significant given the small sample size. However, effect sizes revealed moderate improvements in processing speed (Cohen's d = .72) and verbal memory (Cohen's d = .60) post-HCT, and declines in measures of attention (Cohen's d = -.54) and fine motor speed and dexterity (Cohen's d = -.94). Parents endorsed better quality of life (Cohen's d = .91), less impact of SCD on their family, and less worry about their child's future (Cohen's d = 1.44). Neuropsychological functioning in a sample of children and adolescents treated uniformly with NMA MSD HCT remained stable or improved in most cognitive domains, and improvements in quality of life and family functioning were observed.

Clinical presentation of major sickle cell syndrome in children under 5 years at Kindu hospital environment, Democratic Republic of Congo (DRC)

Sickle cell disease is the most common genetic disorder of hemoglobin in the world today. Screening is the basis of any program aimed at its fight. Faced with the difficulties of implementing screening in countries with limited resources, it is important to resort to alternative strategies, in particular the optimization of clinical suspicion. This study was conducted with the objective of presenting the clinical characteristics of SS sickle cell disease revealed by laboratory screening in pediatric hospitals. A cross-sectional, descriptive study with prospective collection was carried out in 5 health facilities in the city of Kindu in the DRC between December 2, 2019 to October 15, 2020. Our results show that the hospital prevalence of major sickle cell syndrome was 12.7% in the study population. Boys accounted for 53% of cases. The most represented age group was 48 to 59 months with 56.1%. On the clinical level, the examination of our respondents objectified a malnutrition in 36.8% of cases, the presence of frontal bumps in 10.5% of cases, lymphadenopathy in 10.5% of cases, hypertrophy of the tonsils. in 8.8% of cases, conjunctival jaundice in 35.1% of cases, hepatomegaly in 7.0% of cases and splenomegaly in 21.1% of cases. There are significant associations between certain epidemiological characteristics studied in homozygous SS subjects, in particular the age of 48 to 59 months with jaundice (p = 0.012) and splenomegaly (p = 0.028), undernutrition with jaundice (p = 0.037) and the presence of lymphadenopathy (p = 0.013), presence of frontal lumps with enlarged tonsils (p = 0.0001) and hepatomegaly (p = 0.008), splenomegaly with jaundice (p = 0.001) and presence of lymphadenopathy (p = 0.004) and finally hepatomegaly and the presence of lymphadenopathy (p = 0.008). In short, it emerges that many children with major sickle cell syndrome have a less expressive clinical presentation. This is probably linked to the fact that at this age they still have a level of hemoglobin F sufficient to attenuate the impact of hemoglobin S. The associations observed between various clinical parameters show that it is possible to develop a clinic score that can guide the suspicion of the disease and motivate a biological screening.

Sex-based differences in the manifestations and complications of sickle cell disease: Report from the Sickle Cell Disease Implementation Consortium.

IntroductionSex-based clinical outcome differences in sickle cell disease (SCD) remain largely unknown despite evidence that female sex is associated with an increased lifespan. To better characterize sex-based differences in SCD, we assessed pain, treatment characteristics, laboratory measures and complications among males and females currently enrolled in the Sickle Cell Disease Implementation Consortium (SCDIC) registry.MethodsThe SCDIC consists of eight comprehensive SCD centers and one data coordinating center that received funding from the National Heart Lung and Blood Institute to improve outcomes for individuals with SCD. Eligibility criteria included: 15 to 45 years of age and a confirmed diagnosis of SCD. Self-report surveys were completed and data were also abstracted from the participants’ medical records.ResultsA total of 2,124 participants were included (mean age: 27.8 years; 56% female). The majority had hemoglobin SS SCD genotype. Females had worse reports of pain severity (mean (SD) T-score 51.6 (9.6) vs 49.3 (10), p<0.001), more vaso-occlusive episodes (p = 0.01) and a higher occurrence of 3 or more hospital admissions in the past year (30.9% vs. 25.5, p = 0.03). On multivariable analysis, males had higher odds of acute chest syndrome (odds ratio (OR) 1.4, p = 0.002), cardiovascular (OR 1.70, p<0.001) and musculoskeletal (OR 1.33, p = 0.0034) complications and lower odds of depression (OR 0.77, p = 0.0381). Females had higher fetal hemoglobin levels with and without hydroxyurea use (9.6% vs 8.5%, p = 0.03 and 3% vs 2.2%, p = 0.0005, respectively).ConclusionOur data suggests that sex differences in clinical outcomes do occur among individuals with SCD. Future research needs to explore the mechanisms underlying these differences.

Infections and Major Sickle Cell Syndromes at the Ziguinchor Peace Hospital / Senegal

Background: Sickle cell disease is an inherited disorder of hemoglobin. It poses a public health problem in Senegal and mainly affects children and adolescents. Infections are the main cause of morbidity and mortality in children with sickle cell disease. The objective of our work was to assess infections associated with major sickle cell syndromes at the Ziguinchor Peace Hospital (ZPH).&#x0D; Methods: This was a retrospective study, from October 1, 2015 to October 31, 2020. Included were sickle cell patients homozygous SS and heterozygous SC, hospitalized with fever ≥ 39°C, in whom an infectious assessment was performed. Excluded from the study were patients whose complete blood count, C-Reactive Protein, and rapid diagnostic test for malaria were not performed.&#x0D; Results: During the study period, we collected 66 patient files (43 boys and 23 girls). The mean age was 7.6 years [8 months – 21 years]. The population consisted of SS sickle cell disease patients in 98.5% of cases. The average body temperature was 39.6°C [39 – 40.5°C]. The clinical picture on admission was predominantly vaso-occlusive crisis and anemia. The positivity of the bacteriological examinations was 2 cases for the blood culture, 3 cases for the urine culture. The infections were dominated by bronchopneumonia (31.8%); ear, nose and throat infections (31.8%) and osteoarthritis (15.2%). Four children presented with severe malaria and the immediate course was favorable for all patients.&#x0D; Conclusion: otorhinolaryngological infections; Bronchopulmonary and osteoarticular diseases are frequent in children with sickle cell disease at the Ziguinchor peace hospital. we recommend support for the microbiology unit and systematic sampling in febrile sickle cell patients.

Management of Renal Dysfunctions in Escort-HU Study

▪BACKGROUNDRenal impairment is a progressive chronic complication of sickle cell disease (SCD) that begins in childhood and may progress until renal failure. It is responsible for mortality in 12% of SS SCD adults (Tehseen S, 2017).Causes of renal damages in SCD patients are multiple: hemolysis, vaso-occlusive episodes which lead to renal injuries, papillary necrosis, medullary fibrosis and focal segmental glomerulosclerosis (Rees D, 2010).Hydroxycarbamide (hydroxyurea or HU) is a myelosuppressive drug marketed since 1968 for the treatment of hematological malignancies, and authorized since 2007 in Europe as an orphan medicinal product for the prevention of recurrent vaso-occlusive crises and acute chest syndrome in adults and children older than 2 years with SCD. HU also seems to protect kidney function in SCD by decreasing proteinuria (Bartolucci P, 2015).As renal excretion is a pathway of HU elimination (60% of dose excreted in urine), consideration should be given to decrease the dose of HU in patients with renal impairment.We propose to study SCD patients with renal diseases treated with hydroxycarbamide (Siklos) and enrolled in ESCORT-HU (European Sickle Cell Disease COhoRT - HydroxyUrea), European multicenter prospective non interventional study.METHODSFrom January 2009 to June 2017, 1841 patients were enrolled in the ESCORT-HU study. 1016 patients were adults and 824 were children (1 date of birth missing). Among them, renal lesions have been reported in the study database in 220 patients (194 adults, 25 children, 1 date of birth missing).At inclusion the renal status of patients are reported in the electronic Case Report Form (e-CRF) using different clinical approaches. It allows to distinguish patients with a medical history of renal impairment (i.e. patient with renal insufficiency of etiology not reported, with an irreversible and progressive reduction in renal function) from patients with a history of sickle cell (SC) nephropathy (patients with any renal alteration related to SCD and not necessarily irreversible and progressive).RESULTSCompared to the global cohort without any kidney involvement, patients with renal lesions were older (35.8 years vs 21.0 years) as expected, with less children (11.4% vs 50.2%) and mainly with SS genotype (94.5% vs 82.2%) (Table 1).64.1% of patients with renal lesions were already treated with HU other than Siklos before their enrollment in the study, in line with the fact that kidney lesions are correlated with the ageing of the SCD population.HU was initially prescribed at lower doses in SCD patients with renal disease and naïve of HU treatment as recommended. For patients already treated with HU other than Siklos (the dose at enrolment ~ maintenance dose), even if we observed an increase of the dose until maintenance dose, this subpopulation received HU at lower daily doses (Table 2).SCD Patients with kidney diseases reported more frequent and more severe adverse events not related to SCD (AENOTSCD) than patients without renal lesions (2.30 AE per patient vs 1.49 AE per patients and 15.4% of severe AE vs 11.2%) (Figure 1). However these events are less serious (15% of serious AE vs 25% in patients without renal lesions) (Figure 2). Similarly, when focusing on AENOTSCD causally related to HU (as judged by the investigators), patients with renal lesions reported more AE especially in patients with history of renal impairment.As recommended by some guidelines (Habibi 2015, Sharpe 2014), renin-angiotensin system (RAS) inhibitors may be used is SCD patients with renal damage in order to limit the kidney disease progression. In ESCORT-HU study, RAS inhibitors were used in 47.3% of patients with renal lesions whereas it was used in 3.0% of patients without renal lesions. Consistently RAS inhibitors are mainly used in patients with a history of SCD nephropathy (54.54% vs 21.15% in the population with renal impairment) probably because damages in this subpopulation were irreversible (Table 3).CONCLUSION12% of SCD patients, mainly adults, enrolled in the ESCORT-HU study had renal dysfunctions at enrolment. As expected this subpopulation is older than the global population of the cohort. Although HU is prescribed at lower doses, these patients go on to have more adverse events and this justifies a close monitoring of them. Controlled trials are required to evaluate the role of HU on the renal failure. [Display omitted] DisclosuresBartolucci:Novartis US: Membership on an entity's Board of Directors or advisory committees; Addmedica: Research Funding; GBT: Membership on an entity's Board of Directors or advisory committees; Fondation Fabre: Research Funding. Ribeil:Addmedica: Membership on an entity's Board of Directors or advisory committees, Research Funding. Lobitz:Addmedica: Membership on an entity's Board of Directors or advisory committees. Galacteros:Addmedica: Membership on an entity's Board of Directors or advisory committees.

Predictors of Maternal Morbidity Among Participants Enrolled in the Sickle Cell Disease Implementation Consortium Registry

Introduction Pregnancy in sickle cell disease (SCD) is associated with an exacerbation of SCD-related complications and an increased risk of maternal complications. The increased risk is partly due to physiologic adaptations in pregnancy, which include increased metabolic demands and a hypercoagulable state. The maternal death rate for SCD is 629 per 100,000 deliveries, compared to 12 per 100,000 deliveries in black women and 6 per 100,000 deliveries in the general population (Raider et al., 2016). Studies on maternal and perinatal outcomes of patients with SCD present inconsistent and conflicting results. Some studies have reported an increase in maternal complications such as pre-eclampsia, acute chest syndrome and thromboembolic events, while other studies have reported no significant risk in adverse maternal outcomes. The inconsistent findings reported in prior studies may be attributed to small sample sizes and single-centered sites. Our study aims to determine the prevalence and predictors of maternal morbidity among participants enrolled in the SCD Implementation Consortium (SCDIC) registry, which is the largest, most geographically diverse SCD participant sample in the United States. Methods This cross-sectional study included women enrolled in the SCDIC registry who had at least one pregnancy event. The SCDIC is composed of eight academic SCD centers across the United States and one data-coordinating center. Participants were enrolled in the SCDIC registry if they were 18 to 45 years of age and had a confirmed diagnosis of SCD. Enrolled participants completed a series of surveys that collected sociodemographic information, SCD and pregnancy history and data abstractions of participants' medical records was completed. Medical complications queried during pregnancy included: vaso-occlusive episodes, acute chest syndrome, blood transfusion requirement, preeclampsia, maternal diabetes and deep venous thrombosis. Descriptive analysis of sociodemographic, clinical and maternal characteristics was conducted. Bivariate analysis was performed using Chi-Square test, Mann-Whitney U test, t-test, and logistic regressions, as appropriate. A p-value of ≤ 0.05 was considered statistically significant for all analysis. Results The study sample included 743 women who had at least one pregnancy event, and a total of 1066 live births. Almost all women (96.3%) were African American, with a median age of 21 years (inter-quartile range of 19 to 23 years) at first birth. The majority had Hb SS SCD genotype (69.5%; 513 of the 738 with SCD genotype data). Of all reported pregnancies, participants did not use hydroxyurea during conception (78%), and pregnancy (84.5%). Only 2.7 % of the women reported using fertility drugs or assisted reproductive procedures. Seventy five percent of the pregnancies that ended in live births had maternal complications. The leading complications were vaso-occlusive episodes (61.2%), pregnancy requiring blood transfusion(s) (33.2%), preeclampsia (15.4%), deep venous thrombosis (5.6%) and acute chest syndrome (7.7%). When the pregnancies were stratified by SCD genotype, women with Hb SS had a higher occurrence of acute chest syndrome (63.4% vs. 26.7%), transfusion requirement (70.8% vs. 21%) and preeclampsia (66.7% vs 22.4%). In the univariate logistic regressions, multiparous women, with a history of adverse maternal outcomes in a previous pregnancy, had higher odds of vaso-occlusive episodes (OR: 3.42; 95% CI: 2.42-4.94) acute chest syndrome (OR:4.99; 95% CI:2.56- 9.48), transfusion requirement (OR:3.86; 95% CI:2.64- 5.69), and pre-eclampsia (OR:3.36; 95% CI:2.05-5.45). Conclusion In this large multicenter registry, we found pregnant women with SCD have significant maternal complications. Early antenatal care by healthcare providers knowledgeable about risk factors for adverse maternal outcomes in SCD is essential improve maternal and fetal outcomes and reduce the maternal death rate for SCD. Disclosures Hankins: Novartis: Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; MJH Life Sciences: Consultancy, Patents &amp; Royalties; UptoDate: Consultancy; National Heart, Lung, and Blood Institute: Honoraria, Research Funding; LINKS Incorporate Foundation: Research Funding; American Society of Pediatric Hematology/Oncology: Honoraria. Treadwell:Global Blood Therapeutics: Consultancy; UpToDate: Honoraria. King:Amphivena Therapeutics: Research Funding; Bioline: Consultancy; Celgene: Consultancy; Cell Works: Consultancy; Incyte: Consultancy; Magenta Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novimmune: Research Funding; RiverVest: Consultancy; Tioma Therapuetics: Consultancy; WUGEN: Current equity holder in private company. Gordeuk:CSL Behring: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Imara: Research Funding; Ironwood: Research Funding; Novartis: Consultancy. Kanter:SCDAA Medical and Research Advisory Board: Membership on an entity's Board of Directors or advisory committees; AGIOS: Membership on an entity's Board of Directors or advisory committees; BEAM: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; GLG: Honoraria; Jeffries: Honoraria; Cowen: Honoraria; Wells Fargo: Honoraria; NHLBI Sickle Cell Advisory Board: Membership on an entity's Board of Directors or advisory committees; Medscape: Honoraria; Guidepoint Global: Honoraria; bluebird bio, inc: Consultancy, Honoraria; Sanofi: Consultancy. Glassberg:Pfizer: Research Funding; Global Blood Therapeutics: Consultancy; Eli Lilly and Company: Research Funding. Shah:Novartis: Consultancy, Research Funding, Speakers Bureau; Alexion: Speakers Bureau; CSL Behring: Consultancy; Bluebird Bio: Consultancy; Global Blood Therapeutics: Consultancy, Research Funding, Speakers Bureau.

The Prevalence of Uterine Fibroids in African American Women with Hemoglobin SS Sickle Cell Disease as Determined by Pelvic Magnetic Resonance Imaging

This study explores the relationship between the development of uterine fibroids and hemoglobin SS sickle cell disease (SCD) by examining the prevalence of uterine fibroids as detected by pelvic magnetic resonance imaging (MRI) in African American (AA) women with and without SCD. A single-center, retrospective review was performed of all adult AA women at a large, academic medical center who received pelvic MRI from January 1, 2007 to December 31, 2018. Propensity score matching conditional on age and ZIP code evaluated the differences in fibroid prevalence between the two groups. Subanalyses by age in 10-year intervals were also performed. Twenty-one (23.9%) of 88 patients with SCD had fibroids on pelvic MRI versus 1493 (52.1%) of 2868 patients without SCD (p value <0.001). After propensity score matching, 21 (24.7%) of 85 patients with SCD compared to 52 (61.2%) of 85 patients without SCD had fibroids (p value <0.001). Subanalyses in 10-year age intervals showed significance for patients between 30 and 39 years old in which 4 (13.8%) of 29 SCD patients versus 374 (65.3%) of 573 no SCD patients had fibroids (p value <0.001), and for patients between 40 and 49 years old in which 9 (42.9%) of 21 SCD patients versus 667 (73.8%) of 904 no SCD patients had fibroids (p value = 0.002). These findings indicate an overall significantly lower prevalence of uterine fibroids in AA women with SCD, suggesting that SCD may be protective against the development of uterine fibroids in these patients.

Preoperative blood transfusions for sickle cell disease.

Preoperative blood transfusions for sickle cell disease.

Sickle cell disease and COVID-19: Atypical presentations and favorable outcomes.

Sickle cell disease and COVID-19: Atypical presentations and favorable outcomes.

Vitamin D Supplementation Improves Health-Related Quality of Life and Physical Performance in Children with Sickle Cell Disease and in Healthy Children.

No study determined if vitamin D supplementation improves health-related quality of life (HRQL) using pediatric Patient-Reported Outcomes Measurement Information System or physical functioning in type SS sickle cell disease (HbSS). Subjects with HbSS (n = 21) and healthy subjects (n = 23) were randomized to daily oral doses (4,000 vs. 7,000 IU) of cholecalciferol (vitamin D3) and evaluated at 6 and 12 weeks for changes in serum 25 hydroxyvitamin D (25(OH)D), HRQL, and physical functioning. In subjects with HbSS, significant reductions in pain, fatigue, and depressive symptoms and improved upper-extremity function were observed. In healthy subjects, significant reductions in fatigue and improved upper-extremity function were observed. Significant improvements in peak power and dorsiflexion isometric maximal voluntary contraction torques were observed in both groups. In subjects with HbSS, improved plantar flexion isometric maximal voluntary contraction torques were observed. Both groups saw significant improvement in their total Bruininks-Oseretsky Test of Motor Proficiency score. Daily high-dose vitamin D supplementation for African American children with and without HbSS improved HRQL and physical performance.

Deep Vein Thrombosis of the Upper Limb: About 6 Cases Collected in Dakar

Deep vein thrombosis of the upper limb is a rare location of venous thromboembolic disease. Data on this form of thrombosis are limited. We report six cases collected in Dakar. The sex ratio was 0.5 and the average age was 27.6 years with extremes of 17 and 39. Painful limb edema was the most constant sign and involved the non-dominant limb in almost all patients. Thrombosis occurred in a field of peripartum cardiomyopathy in two patients and SS sickle cell disease in one patient taking oral contraception. There was neither cancer nor venous catheter in medical history. The diagnosis was made by venous Doppler ultrasound in all patients. Subclavian involvement was the most common. The thrombophilia assessment, done for two patients, was normal. It was about exertion thrombosis on three (3) patients. All the patients had received antivitamin K treatment relaying a low molecular weight heparin. Venous limb compression was associated with anticoagulation for all patients. The treatment duration was six (6) months. There were no reports of pulmonary embolism or death. One patient presented a post-thrombotic syndrome.

A Multidimensional Electronic Hydroxyurea Adherence Intervention for Children With Sickle Cell Disease: Single-Arm Before-After Study.

BackgroundHydroxyurea is a disease-modifying medication for patients with sickle cell disease (SCD). Despite demonstrated efficacy, hydroxyurea nonadherence in clinical practice is common and results in worse health outcomes for nonadherent patients. Mobile Directly Observed Therapy (Mobile DOT) is a pilot-tested, electronic, multidimensional hydroxyurea adherence intervention for children with SCD. Mobile DOT includes sending daily text message reminders to patients to take hydroxyurea, patients recording and sending daily videos that capture their hydroxyurea administrations for the research team to review and track adherence, providing personalized feedback to patients about their adherence, and providing small monetary incentives to patients if they achieve high hydroxyurea adherence.ObjectiveThis study aimed to determine if Mobile DOT increases hydroxyurea adherence in children with SCD and to explore its impact on hematologic and clinical outcomes.MethodsThis was a single-arm, 6-month intervention study of patients with SCD on hydroxyurea who were aged ≤19 years and reported having access to an electronic device. Participants’ hydroxyurea adherence when they received Mobile DOT was compared with their adherence 6 months before and after receiving Mobile DOT. Participants’ medication possession ratio (MPR) was calculated from their pharmacy dispensing records and was used to measure adherence. Laboratory and clinical outcomes were abstracted from participants’ electronic medical records. Infrequently hospitalized patients who received at least 160 days of the intervention were considered to be engaged participants.ResultsOf 91 patients who were approached, 55 enrolled and 34 engaged with Mobile DOT. The median age of the engaged participants was 10 years (range 2-18.8 years), and 21 (62%, 21/34) participants were male, 28 (82%, 21/34) had hemoglobin SS SCD, and 19 (56%, 19/34) were prescribed hydroxyurea for at least a year before enrollment. With Mobile DOT, engaged participants’ median MPR increased from 61.7% to 84.4% (P<.001) and significantly more (67% vs 30%; P=.002) achieved ≥80% hydroxyurea adherence compared with baseline values. Engaged participants’ mean fetal hemoglobin (HgbF) levels and mean corpuscular volumes (MCV) improved significantly after 6 months of Mobile DOT (P=.04 and P=.001, respectively), but their adherence, HgbF levels, and MCV returned to baseline values during the 6 months after the intervention. Hospitalizations and the clinical outcomes that were measured occurred infrequently during the study. Nonengagement was associated with being female and having a recent SCD complication. In addition, having insufficient electronic data, being unable to quickly complete Mobile DOT each day, and not perceiving that Mobile DOT was beneficial may have further decreased engagement.ConclusionsMobile DOT shows promise as an effective intervention for some children with SCD. Modifications that may improve recruitment, reduce attrition, and increase engagement were identified and could increase the impact that Mobile DOT has on children with SCD.Trial RegistrationClinicalTrials.gov NCT02578017; https://clinicaltrials.gov/ct2/show/NCT02578017

(211) Deep Pain Mechanisms in Sickle Cell Disease

Sickle Cell Disease (SCD), an autosomal recessive red blood cell disorder, affects more than 100,000 individuals in the US. Deep pain that appears to stem from muscle and bones is a major complaint of patients with SCD and very little is known about putative mechanisms that cause this deep pain. To assess this pain, we used the Townes HbSS (SS) transgenic mouse model of SCD to perform behavioral assays including evoked withdrawal responses to gastrocnemius muscle pinch and the inverted screen hang, a potential measure of muscle or bone pain. For the muscle pinch assay, SS mice exhibited lower withdrawal thresholds than Townes AA controls. Furthermore, there was a sex difference between SS males and SS females in their withdrawal thresholds where females had higher sensitivity and greater pain-like behaviors than males. For the inverted screen hang assay, SS mice had significantly lower total hang time and more time on 3 paws or less compared to AA controls. Together these data suggest that these mice may experience greater deep pain. Because the TRPV1 channel has been shown to contribute to mechanical hypersensitivity in SCD mice, we used the selective and potent TRPV1 inhibitor A-425619 in behavioral assays. Intraperitoneal injection of A-425619 (100µmol/kg) partially reversed the sensitized muscle pinch withdrawal thresholds in both sexes of SS SCD mice, with a greater effect on males than in females. To further assess mechanisms underlying the sensitization in SCD mice, calcium imaging of lumbar DRG sensory neurons was performed to begin to investigate whether there is increased sensitization of sensory neurons to endogenous metabolites that could act on TRPV1, ASIC3, and P2X channels. In conclusion, these data suggest that the Townes SS mouse model of SCD has increased deep pain sensitivity compared to controls and this sensitivity appears to be partly mediated by TRPV1.

Chronic blood exchange transfusions in the management of pre-capillary pulmonary hypertension complicating sickle cell disease.

The long-term effects of chronic blood exchange transfusions (BETs) on pre-capillary pulmonary hypertension complicating sickle cell disease (SCD) are unknown.13 homozygous SS SCD patients suffering from pre-capillary pulmonary hypertension and treated by chronic BETs were evaluated retrospectively. Assessments included haemodynamics, NewYork Heart Association Functional Class (NYHA FC), 6-min walk distance (6MWD) and blood tests.Before initiating BETs, all patients were NYHA FC III or IV, median (range) 6MWD was 223 (0-501) m and median (range) pulmonary vascular resistance (PVR) was 3.7 (2-12.5) Wood Units. After a median number of 4 BET sessions, all patients had improved to NYHA FC II or III. Significant improvements in haemodynamics were observed, including a decrease in PVR (p=0.01). There was a trend to higher 6MWD (p=0.09). Median (range) follow-up time after initiation of BETs was 25 (6-53) months. During this period, two patients decided to stop BETs. One of them died from acute right heart failure and the other experienced worsening pulmonary hypertension. Two other patients died during follow-up at 25 and 54 months after BET initiation.Chronic BETs may be a potential therapeutic option in pre-capillary pulmonary hypertension complicating SCD, leading to significant clinical and haemodynamic improvements. These data must be confirmed in a prospective study.

Muscle Strength, Power, and Torque Deficits in Children With Type SS Sickle Cell Disease.

In African-American children aged 5 to 17 years with and without type SS sickle cell disease (SCD-SS), dominant hand maximal handgrip strength, peak power, and plantar flexion isometric maximal voluntary contraction (MVC) torque were compared with adjustments for body size and composition. Children with SCD-SS (n=21; age, 11±1 y) compared with healthy control children (n=23; 10±1 y) did not differ by age, sex, or maturation stage, but had significantly lower Z scores for height, weight, body mass index, arm circumference, upper arm muscle area, and lean mass-for-height. Children with SCD-SS had significantly lower unadjusted handgrip strength (16±2 vs. 23±2 kg, P<0.01), peak power (1054±107 vs. 1488±169 W, P<0.04) and MVC torques at 2 angles (10 degrees: 27±3 vs. 42±5 Nm; 20 degrees: 21±3 vs. 34±4 Nm; all P<0.05). Performance decrements persisted when handgrip strength was adjusted for lean body mass and fat mass explaining 66% of the variance; peak power adjusted for age, lean body mass, fat mass, and height explaining 91% of the variance; and the highest MVC torque (10-degree angle) adjusted for left leg length, lean mass-for-height, and fat mass-for-height Z scores explaining 65% of the variance. This suggests additional factors contribute to the attenuated anaerobic performance.