Adult Sickle Cell Disease Patients Research Articles

Prevalence of Pulmonary Hypertension among Sudanese Patients with Sickle Cell Disease

Background Sickle Cell Disease (SCD) is a hereditary condition characterized by aberrant red blood cell morphology, leading to persistent hemolytic anemia. The consequential impact of SCD on the pulmonary vasculature can result in pulmonary hypertension (PHT), a severe complication that detrimentally affects the well-being and survival of individuals with SCD. The prevalence and risk determinants of PHT in SCD patients exhibit variations across diverse geographical regions and populations. This study aims to ascertain the prevalence of PHT among Sudanese SCD patients and identify associated factors. Methods A cohort of thirty-one adult sickle cell disease (SCD) patients, as confirmed by hemoglobin electrophoresis, were recruited for participation in this cross-sectional study. Comprehensive data encompassing demographic, clinical, and laboratory parameters were collected. Doppler echocardiography was employed to quantify pulmonary arterial systolic pressure (PASP) and evaluate right ventricular size and function. Results Within our cohort, the prevalence of PHT was 29%. Active cigarette smoking demonstrated a significant association with PHT (P=0.042), while hydroxyurea therapy exhibited no noticeable impact on PHT (P=0.612). Conclusion Our investigation revealed a PHT prevalence of less than one-third in our SCD patient population, aligning with prior studies. Notably, independent of other factors, cigarette smoking emerged as a distinct risk factor for PHT in SCD patients. This highlights the potential utility of smoking cessation as an intervention to delay the onset of this condition. However, further research is imperative to elucidate the mechanisms through which smoking contributes to PHT development in individuals with SCD.

Genotypic Variations in Exercise-Induced Hemoglobin Oxygen Desaturation in Sickle Cell Disease: The Role of Hemoglobin Levels

Background: Sickle cell disease (SCD) presents abnormal hemoglobin S (HbS) and frequent vaso-occlusive crises. Previous studies reveal exercise intolerance in SCD patients. However, the role of exercise-induced hemoglobin oxygen desaturation (EIHOD) and its predictors remains unclear. This study investigates EIHOD in adult SCD patients, focusing on potential predictors, aligning with the hypothesis that EIHOD is prevalent and varies across genotypes, with hemoglobin as a predictor. Methods: A cross-sectional study was conducted on adult patients with HbSS and HbSC genotypes in a steady state at the Korle-Bu Teaching Hospital, Ghana. Clinical, hematological, and haemolytic markers were assessed. Lung function was evaluated through spirometry, and a six-minute walk test (6MWT) was performed to assess EIHOD. Logistic regression was used to identify predictors of EIHOD. We hypothesis that, EIHOD is common in SCD, varying across genotypes, with hemoglobin predicting its occurrence. Results: The prevalence of EIHOD was 41% in HbSS patients and 36.1% in HbSC patients. No significant differences were observed in age, white blood cell count, platelet count, hemolytic markers, hemoglobin levels, or lung function parameters between SCD patients with and without EIHOD. In the logistic regression model, none of the variables predicted EIHOD in HbSS patients. In HbSC patients, reduced hemoglobin was the only predictor of EIHOD (OR=0.551; 95% CI=0.315-0.964; p-value= 0.037). Discussion: The study highlights a high prevalence of EIHOD within the HbSS genotype, emphasizing the importance of hemoglobin levels as a predictor of EIHOD in SCD. Contrarily, hemolytic markers and lung function were not predictors of EIHOD across either genotype. These results suggest the potentially heightened significance of EIHOD-related complications in patients with the HbSS genotype. Conclusion: EIHOD is common in SCD, more so in HbSS. Reduced hemoglobin predicts EIHOD in HbSC. Lung function and hemolytic markers don't. Understanding the impact of EIHOD in SCD may guide interventions to improve exercise tolerance and reduce complications in this population. No Funding. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Pulmonary Hypertension in Sickle Cell Disease: Novel Findings of Gene Polymorphisms Related to Pathophysiology.

Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD), affecting 6-10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of this disease. However, questions remain, particularly regarding the clinical heterogeneity of the disease in terms of symptoms, complications, and survival. Beyond the classical mechanisms that have been thoroughly investigated and include hemolysis, nitric oxide availability, endothelial disorders, thrombosis, and left heart failure, attention is currently focused on the potential role of genes involved in such processes. Potential candidate genes are investigated through next-generation sequencing, with the transforming growth factor-beta (TGF-β) pathway being the initial target. This field of research may also provide novel targets for pharmacologic agents in the future, as is already the case with idiopathic PH. The collection and processing of data and samples from multiple centers can yield reliable results that will allow a better understanding of SCD-related PH as a part of the disease's clinical spectrum. This review attempts to capture the most recent findings of studies on gene polymorphisms that have been associated with PH in SCD patients.

Electrocardiographic Abnormalities in Adult Homozygous Sickle Cell Disease Patients in Nnamdi Azikiwe University Teaching Hospital, Nnewi, South-Eastern Nigeria

Background; Sickle cell anaemia is the most common monogenic hematologic disorder in Nigeria. Cardiovascular pathology, resulting in electrocardiographic abnormalities are a common finding in adult sickle cell patients.
 Objective; This study investigated the pattern of electrocardiographic (ECG) abnormalities in steady state adult sickle cell anaemia (HbSS) patients and compared the findings with that of age and sex matched Haemoglobin AA(HbAA) controls.
 Methodology; Fifty steady state adult HbSS participants were recruited from the haematology clinic at Nnamdi Azikiwe University Teaching Hospital while fifty age and sex matched HbAA controls were recruited from the hospital community. Participants underwent resting 12 lead ECG using a Schiller CARDIOVIT AT-1 ECG machine. Data was analyzed using Statistical Package for Social Sciences version 21.
 Results; The prevalence of ECG abnormalities amongst the adult sickle cell participants and controls was 70% and 10% respectively. ECG abnormalities were more common amongst male sickle cell participants and left ventricle hypertrophy was the most frequent ECG abnormality detected.
 Conclusion; There is a high prevalence of ECG abnormalities amongst adult sickle cell anaemia patients. Regular Electrocardiography is recommended for early detection of these abnormalities for early treatment and improved quality of life.
 Keywords: Electrocardiographic Abnormalities, Sickle Cell Disease Patients, Nnamdi Azikiwe University, Haemoglobin AA

Montreal cognitive assessment in Brazilian adults with sickle cell disease: The burdens of poor sociocultural background.

Sickle cell disease (SCD) patients are at higher risk of developing silent cerebral infarcts and overt stroke, which may reflect cognitive impairment, functional limitations, and worse quality of life. The cognitive function of Brazilian adult SCD patients (n=124; 19-70 years; 56 men; 79 SS, 28 SC, 10 S/β0, 7 S/β+) was screened through Montreal Cognitive Assessment (MoCA) and correlated the results with possible predictive factors for test performance, including sociocultural, clinical, laboratory data and brain imaging. The Median MoCA score was 23 (8-30); 70% had a 25-or-less score, suggesting some level of cognitive impairment. There were no significant associations between MoCA results and any clinical or laboratory data in SS and SC patients; however, a significant correlation (P=0.03) with stroke was found in HbS/β-thalassemic patients. Correlations were further detected according to sociodemographic conditions, such as age (r=-0.316; P<0.001), age at first job (r=0.221; P=0.018), personal (r=0.23; P=0.012) andper capitafamiliar incomes (r=0.303; P=0.001), personal (r=0.61; P=0), maternal (r=0.536; P=0), and paternal educational status (r=0.441; P=0). We further sought independent predictors of performance using multivariable regressions and increased education was an independent predictor of better scores in MoCA (0.8099, 95% confidence interval [CI]: 0.509-1.111). Brain imaging analysis showed significant and progressive atrophy in important cerebral areas related to memory, learning, and executive function. These data point to the high prevalence and impact of cognitive decline in adult SCD patients, mirrored in brain atrophic areas. It is also possible to observe the influence of sociodemographic conditions on patients' cognitive performances and the need for creating focused therapeutic plans that address these deficiencies. Moreover, the absence of a significant correlation of MoCA values with stroke in the SS and SC groups may be related to the worst sociocultural and economic conditions of the Brazilian African descent population, in which the impact of low educational stimulation on cognitive function can outweigh even the anatomical damage caused by the disease.

Poor Sleep Quality in Jamaican Adults With Sickle Cell Disease: Prevalence, Risk Factors, and Association With Quality of Life

Poor sleep and chronic illnesses have a bidirectional relationship where presence of one can worsen the other. Sickle cell disease (SCD) is associated with significant morbidity and early mortality. In this study, we examine sleep quality, its predictors, and its association with quality of life in Jamaican adults with SCD. This cross-sectional study evaluated 177 well adult SCD patients for sleep quality using The Pittsburgh Sleep Quality Index (PSQI) and quality of life using the Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me). Multiple linear regression models examined the predictors of poor sleep quality. The mean global PSQI score was 6.9 (SD 4.2) with 56.5% having poor sleep quality. Women had significantly worse scores for sleep efficiency (p 0.005), sleep latency (p 0.03) and higher use of sleeping medications (p 0.02). Those overweight/obese had significantly worse subjective sleep quality (p 0.001) and sleep efficiency (p 0.05). In multivariate regression analysis, overweight individuals had poorer sleep quality (OR: 2.9; 95% C.I.: 1.07, 7.88) than those with normal weight whereas those unemployed and looking for a job had lower prevalence of poor sleep quality (OR 0.2; 95% C.I.: 0.05, 0.77) compared to employed individuals. Participants with good sleep quality had significantly better functioning in all 5 domains of the ASCQ-Me. In conclusion, persons with SCD who are overweight or obese are at increased risk of poor sleep which can negatively affect quality of life. Patient populations and healthcare providers will need to manage the emerging burden of overweight/obesity.

Cost-effectiveness of l-glutamine versus crizanlizumab for adults with sickle cell disease: model focused on reducing pain episode costs from Qatar's healthcare perspective.

Treatment options for preventing vaso-occlusive crises among sickle cell disease patients are on the rise, especially if hydroxyurea treatment has failed. This economic analysis is conducted to assess the comparative clinical effectiveness, safety, and acquisition cost of l-glutamine and crizanlizumab for older adolescents and adults (⩾16 years old) with sickle cell disease in Qatar, with an emphasis on treatment costs and acute pain crises. We conduct a decision-tree model, where we compare the clinical and economic outcomes of two novel Food and drug administration (FDA)-approved medications which are available in Qatar; l-glutamine and crizanlizumab over a time horizon of 1 year in a hypothetical cohort of adult sickle cell disease patients from a Qatar healthcare perspective. The main outcome is incremental cost per sickle cell disease-related acute pain crises averted. Model clinical parameters were derived from individual drug randomized trials, published literature, whereas cost parameters from Qatar healthcare payer system (2020-2021). A sensitivity analysis was carried out, and the study results were robust around model inputs. Costs were converted to 2020 US dollars. Study results showed that both treatment modalities' costs were the main driver of this analysis, with an average annual cost of the treatments per patient being $189,014 for crizanlizumab (5 mg/kg), $143,798 for crizanlizumab (2.5 mg/kg), and $74,323 for l-glutamine. The probability of no first-time sickle cell disease-related vaso-occlusive crises averted was 0.001/year for glutamine, 0.26/year for crizanlizumab (5 mg/kg), and 0.34/year for crizanlizumab (2.5 mg/kg). Lower dose crizanlizumab (2.5 mg/kg) dominated the higher one (5 mg/kg). The incremental cost-effectiveness ratio of crizanlizumab (2.5 mg/kg), when compared to l-glutamine was $81,265 per sickle cell disease-related vaso-occlusive crises averted. When comparing crizanlizumab (5 mg/kg) and l-glutamine, crizanlizumab (5 mg/kg) showed higher efficacy, yet the crizanlizumab incremental cost-effectiveness ratio was at $459,620 than l-glutamine. Crizanlizumab (2.5 mg/kg) may be a cost-effective intervention, yet it is not the approved dose for preventing vaso-occlusive crises in adolescents and adults with sickle cell disease. Crizanlizumab (5 mg/kg) was more cost-effective than the approved l-glutamine per sickle cell disease vaso-occlusive crisis prevented. Of note, we primarily focused on modeling acute vaso-occlusive pain, which limited our ability to consider other key outcomes in sickle cell disease.

Ineffective Erythropoiesis with Aging in Adults with Sickle Cell Disease

INTRODUCTION In the United States, life expectancy for adults with sickle cell disease (SCD) has improved over the last several decades and providers are now encountering increasing numbers of patients in the fourth, fifth and sixth decades. One notable feature of older SCD patients is lower ‘steady state’ hemoglobin (Hb) levels. Although it is well established that lower Hb levels are associated with increased adverse outcomes including pulmonary hypertension, stroke, cognitive decline, acute chest syndrome, frequency of vaso-occlusive crisis and shortened survival, a full understanding of the mechanisms accounting for the more prevalent and severe anemia in older SCD patients remains to be elucidated. Involved factors may include the long-term effect of chronic hemolysis, age-associated increased inflammation, progressive renal insufficiency and an age-related decline in nutritional adequacy. Despite lacking a uniform explanation for anemia applicable to individual SCD patients, it remains a management goal to optimize Hb level as possible within constraints associated with the development of secondary hemochromatosis. We postulate that the pathways to anemia in SCD patients may change with advancing age and that a better understanding of these pathways may result in a more directed intervention for the older sickle cell patient. METHODS Adult patients visiting Inova Adult Sickle Cell Center over a 6-month period (January through June 2023) with Hb levels below 9 g/dL were evaluated by a contemporary hematologic panel that included complete blood count with differential, reticulocyte count, comprehensive metabolic panel (included total bilirubin and creatinine), and lactate dehydrogenase (LDH). The reticulocyte proliferation index (RPI) was determined utilizing a readily accessible calculator (MedCalc) and a univariate regression analysis was performed for RPI against age. An RPI of &amp;lt; 2 was considered evidence for hypoproliferative anemia. RESULTS Of the 139 unique adult SCD patients visiting our clinic in this 6-month period, 60 had Hb levels equal to or below 9 g/dL. Of these, 8 patients had serum creatinine levels ≥ 1.5 mg/dL and were considered to have hypoproliferative anemia based on renal insufficiency. Among the remaining 52 patients, the mean age was 34.9 years, mean Hb was 7.49 g/dL and the mean RPI was 2.52. In patients with age ≤ 40 years, mean RPI was 2.74, compared to mean RPI of 1.61 in patients with age &amp;gt; 40 years. The mean Hb was 7.55 g/dL vs 7.21 g/dL mean total bilirubin was 3.08 mg/dL vs 2.15 mg/dL and mean LDH was 509 U/L vs 434 U/L in these two age groups (Fig 1). Regression analysis indicated that an increase in age corresponded to a reduction in RPI at 95% confidence level (Fig 2; regression coefficient: -0.04; 95% CI: -0.08 - -0.003; p-value: 0.03). CONCLUSION From the data we gathered, we conclude that despite chronic hemolysis in sickle cell disease, low RPI and ineffective erythropoiesis are evident to some extent in the majority of adult SCD patients even in the absence of renal failure and this significantly increases with age. Older patients with SCD are more likely to have ineffective erythropoiesis. We speculate that this may be evidence for age-associated bone marrow failure not unlike myelodysplasia (MDS) which occurs with increased frequency in the general population with advancing age. If future studies confirm disordered erythropoiesis, clonal hematopoiesis, or other markers of MDS, novel treatments known to be effective in patients with MDS may be examined in selected anemic SCD patients.

A Comprehensive Echocardiographic Portrait of Adult Sickle Cell Disease Patients in the Modern Era

Background Cardiovascular complications, especially pulmonary hypertension, are a known cause of mortality in patients with sickle cell disease (SCD). With advances in medicine and the introduction of various disease-modifying medications, the incidence and prevalence of cardiovascular complications are poorly documented. Aim To determine rates of cardiovascular complications in patients with SCD in the modern era of disease-modifying medications in a single center. Method We performed a retrospective observational single-center study of patients with SCD: all genotyped and ≥16 years old who had a recent echocardiogram performed during the study period of 2019-2023. Demographics, echocardiogram results, and laboratory findings were collected and analyzed. Descriptive statistics are presented in percentages, medians, and interquartile ranges. An unpaired Student's t-test and Fisher's exact test were used to determine, where appropriate, the level of significant differences among continuous and categorical variables, respectively, with p value &amp;lt;0.05 considered statistically significant. Data was analyzed using GraphPad Prism version 9.0.2. Results As of June 2023, 80 patients (38 male and 42 female, median age 30 years) had undergone a routine transthoracic echocardiogram. Sixty-five patients had the HbSS genotype, 8 HbSC, and 7 HbSB null. Sixty-one patients had received at least one treatment, and 19 (24%) were on concurrent therapy. Hydroxyurea was the common SCD-modifying therapy that the patients received (51 patients), followed by L-glutamine and voxelotor (11 each) and crizanlizumab (9 patients). In total, 56 (70%) patients had at least one cardiac abnormality. The most common cardiac abnormality was left atrial dilatation (41%), followed by left ventricular hypertrophy (33%), right atrial dilation (24%), and left ventricular dilatation (23%). Pulmonary hypertension was present in 30 (38%) patients with tricuspid regurgitation velocity (TRV) ≥2.5 msec (Table 1). The cohort of patients with pulmonary hypertension tended to be older (median age 31 years, p=0.0357), have a higher creatinine level (median 0.8, p=0.0414), and have coexisting echocardiographic abnormalities such as left atrial dilatation (70% vs. 24%, p&amp;lt;0.0001) or right atrial dilatation (40% vs. 14%, p=0.0136) than SCD patients without pulmonary hypertension (Table 2). Conclusion We present a comprehensive echocardiographic assessment of patients with SCD. Despite advances in the treatment of SCD, there remains a high prevalence of cardiac involvement in SCD patients. We found out that 70% of the patients we reviewed had at least one cardiac abnormality on echocardiography. Left atrial dilatation and left ventricular hypertrophy were the most common cardiac abnormalities noted. Pulmonary hypertension was observed in 37.5% of patients with co-existing right and left atrial enlargement. Larger studies are needed to corroborate these findings.

Atrial Arrhythmia in Sickle Cell Anemia: A Missing Piece to Prevent Cerebrovascular Complications?

Background: Although Sickle Cell anemia (SCA) patients carries an increased risk of stroke and an important left atrial (LA) remodeling, the reality of atrial arrythmia (AA) has never been prospectively assessed. Purpose: The aim of this study was to identify the prevalence and predictors of atrial arrhythmia in SCA patients among Drepacoeur registry. Methods: From January 2019 to November 2022, consecutive adult patients with SCA were referred to the physiology department to specifically analyze cardiac function and were prospectively included. They underwent a 24-hour electrocardiogram monitoring (ECG-Holter), transthoracic echocardiography, and laboratory tests on the same day. The primary end point was the occurrence of AA, defined by the presence of excessive supraventricular ectopic activity (ESVEA) on ECG-holter (i.e. &amp;gt;720 premature atrial contractions [PACs] or any run ≥ 20 PACs), recent history of paroxysmal atrial fibrillation (AFib), of persistant AFib. Results: Overall, 130 patients were included. Mean age was 45±12 years, 48% were male. AA was observed in 34 (26%) patients (17 with more than 720 PACs/day, 6 with at least a run ≥ 20 PACs, 11 with recent history of paroxysmal AFib and 5 with persistant AFib). Ageing (52±9 vs. 42±12 years, P=0,004), LA dilation (LAV i, 71±24 vs. 52±14 ml/m², P&amp;lt;0.001) and history of stroke without underlying cerebral vasculopathy (23% vs. 7%, P=0.04) were independently associated with AA. Age and LAV i correlated with PAC load on ECG-holter (R=0,56, P&amp;lt;0,001 and R=0,33, P&amp;lt;0.001 respectively). Interestingly n age over 47 years or a LAV i &amp;gt;55ml/m² could predict AA with a positive prective value of 33% and a negative one of 92%. Conclusion: Atrial arrythmia is common in adult SCA patients and is associated with ageing, LA remodeling and considerably increases the risk of ischemic stroke. This study provides tools for early detection of AA and prevent cardiac and cerebrovascular dramatic complications in this highly vulnerable population.

Optimizing Albuminuria Assessment in Patients with Sickle Cell Disease: Insights from the Sikamic Study

Background Patients with sickle cell disease (SCD) are at increased risk of developing renal complications, making early detection and management of these issues critical. Albuminuria has been identified as a relevant biomarker associated with chronic kidney disease (CKD) progression in SCD, as demonstrated in several studies (Gonzalez et al., 2017; Guasch et al., 2018). Quantification of albuminuria is typically performed using the urine albumin-to-creatinine ratio (ACR). However, this measurement is not without its challenges, as variability in results can occur due to several factors, including analytical method, varying sampling conditions, and biological and medical factors such as physical activity, diurnal changes, diet, and hydration, which require the collection of multiple consecutive first morning samples. Studies have shown that the use of ACR from first morning urine samples provides results comparable to the gold standard 24-hour urine collection, with improved precision and less intra-individual variability than random urine samples typically collected during clinic visits (Witte 2009, Jermendy 2001, Lambers 2008). Collecting more urine samples generally improves precision and statistical power, but Kröpelin et al (2025) showed that collecting more than three consecutive urine samples does not significantly improve precision. Material and method The ongoing SIKAMIC study is a phase IIb, international (France and Africa), double-blind, randomized, placebo-controlled trial. The study aims to determine the effect of hydroxycarbamide on albuminuria level after 6 months of treatment in SCD adult patients. Here, we analyzed the variability of ACR in all patients pre-selected for the study. Microalbuminuria is commonly considered the first clinical indicator of glomerular damage in SCD. As per the KDIGO (Kidney Disease: Improving Global Outcomes), microalbuminuria is characterized by an ACR ranging from 3 to 30 mg/mmol, while macroalbuminuria refers to an ACR greater than 30 mg/mmol. For SIKAMIC study, patients with an ACR above 3 mg/mmol and below 100 mg/mmol were included. ACR was measured in first morning urine samples over three consecutive days. Patients were instructed to collect these samples at home, which were either collected by a hospital courier or brought to the hospital/laboratory by the patient for analysis. Estimated glomerular filtration rate (eGFR) was calculated using the CKD EPI formula without ethnic criteria. Means and standard deviations of the three measurements were calculated per patient, and a reproducibility test was performed using Mixed Effect Model and Bland Altman analyses (Graphpad Prism 9). Results Out of the initial 179 patients pre-selected for the study (59 from France and 120 from Africa) 99 patients (34 in France and 65 in Africa) met the inclusion criteria and were enrolled in the SIKAMIC study. Pre-selected patients from Africa were younger than patients from France with a mean age of 28.3 years and 33.8 years respectively (p&amp;lt;0.001). However, the mean ACR did not differ between groups (11.8 vs 12.7 mg/mmol; p=0.8) as observed for the mean eGFR value (123 vs 120.9; p=0.75). Additionally, the sex ratio was similar between groups (0.62 vs 0.67). For all patients, the mean ACR was 14.6, 17.3 and 15.6 mg/mmol on days 1, 2 and 3, respectively, with no significant difference (p=0.43; Figure 1 : A). The mean standard deviation of ACR between day 1, 2 and 3 was 6.8 mg/mmol, suggesting good consistency and reproducibility of the ACR measurements over the three days. Bland-Altman plots are shown in Figure 1 for the total population (n=161; 1B), microalbuminuric (1C; n=86) and macroalbuminuric (1D; n=11) patients, illustrating the agreement of ACR measurements within these subgroups. Conclusion : The SIKAMIC study contributes valuable insights into the evaluation of albuminuria in SCD patients. The reproducibility of the ACR appears to be sufficient to allow satisfactory monitoring on a single morning measurement in SCD routine care, both in Africa and Europe population of SCD patients.

Benefit of Inpatient Pain Plan Utilization on Hospital Length of Stay in Adolescents and Young Adults with Sickle Cell Disease

Introduction Vaso-occlusive crisis (VOC) is the most common manifestation of sickle cell disease (SCD) and the most common cause for emergency department (ED) visits and hospital admissions. VOC accounts for approximately 230,000 annual admissions in children with SCD. Patients with SCD face inconsistent analgesic management, leading to high inpatient healthcare utilization and financial burden for healthcare institutions. Furthermore, patients describe their pain management as the area of their care in most need of improvement. A prospective longitudinal cohort study showed that implementation of individualized pain plans in adult patients with SCD significantly decreased the duration of VOC hospital stays by 1.2 days. A similar study in children showed no change in duration of hospital stay, however the study was limited by a small sample size. We hypothesized parallel results to the prior adult study in adolescent and young adult (AYA) SCD patients. Methods At UCSF Benioff Children's Hospital Oakland, we implemented inpatient pain plans for SCD patients with frequent VOC admissions (i.e., &amp;gt;1 VOC admission in the prior year or complicated VOC admission history). Pain plans are individualized and embedded into the patient's electronic health record. These plans include detailed daily analgesic recommendations with the general recommendation for discharge on day 5 of the pain plan. After IRB approval, we performed a retrospective chart review of SCD patients with individualized inpatient pain plans initiated between November 2017 and April 2022. We recorded baseline demographic information including age at pain plan initiation, SCD genotype and sex. We assessed length of inpatient hospitalization for VOC admissions in the year prior and the year after pain plan initiation for each individual patient. We also noted number of admissions secondary to VOC during this two year time period. Results Twenty-six patients with SCD and individualized pain plans were identified (Table 1). Average length of hospital stay for VOC was significantly decreased in the year after inpatient pain plan initiation (Table 2). There was a trend towards increased admissions due to VOC in the year after inpatient pain plan initiation (Table 2). Conclusions Similar to the prior adult study in SCD patients, we found significantly reduced inpatient length of hospitalization after initiation of an inpatient pain plan for AYA patients with SCD and VOC. Although there was a trend towards increased hospitalizations in the year after inpatient pain plan initiation, this was likely secondary to the average patient age with an expected increased in VOC year over year. The National Heart, Lung, and Blood Institute (NHLBI) SCD guidelines recommend an individualized prescribing and monitoring protocol be written by a SCD provider and used in patients withVOC to promote effective, timely, and safe analgesic management. We further demonstrate that individualized pain plans for AYA patients with SCD can decrease length of hospital stay due to VOC, likely secondary to more effective pain management recommendations that have been prior agreed upon by the patient/family and SCD provider. We currently are calculating morphine equivalents and hypothesize total opioid utilization will be concomitantly decreased due to this significantly decreased length of hospitalization.

Steady-State Von Willebrand Factor Antigen Levels Predict Low Platelet Counts and Risk for Complications in Hospitalizations for Painful Sickle Cell Vaso-Occlusive Episodes

We previously reported that a &amp;gt;20% decline in platelet counts from steady state to presentation predicted severe complications during hospitalization for vaso-occlusive pain crisis (VOC) in 130 adult sickle cell disease (SCD) patients. 1 Sharp platelet decline in acute chest syndrome was reported to be accompanied by large von Willebrand Factor (VWF) aggregates adherent to pulmonary vascular endothelium in SCD. 2 A prospective study of 24 SCD patients found a significant increase of VWF reactivity in VOC admissions relative to steady state, which correlated with low platelet counts and the development of acute chest syndrome. 3 We aimed to investigate the role of steady-state VWF antigen level and ADAMTS13 activity as predictors of platelet count decline and severe complications in VOC admissions. Plasma levels of VWF antigen and ADAMTS13 activity were measured 4 for 56 patients at steady-state outpatient visits (Baseline). VWF antigen was expressed as fold increase or decrease from the concentration in normal pooled plasma of 12.2 ug/ml; ADAMTS13 activity was expressed as fold of the value from normal pooled plasma which was considered 100% activity. Electronic records of VOC admission that occurred &amp;gt;21 days after Baseline were reviewed. Exclusion criteria included non-VOC admissions defined as elective admission for surgery, admission for accident or injury, admission for delivery of an infant, or admission with a pain score &amp;lt;8/10 at presentation. 5 A total of 98 qualifying admissions were identified. Severe complication during the admission was defined as having any of the following: 1) acute chest syndrome, new infiltrate on chest X-ray, or use of ventilator; 2) acute kidney injury; 6 3) acute liver injury; 7 4) thrombotic or hemorrhagic stroke; 5) venous thromboembolism including deep vein thrombosis, atrial thrombosis, and pulmonary embolism; 6) need for transfer to the intensive care unit; 7) need for exchange blood transfusion; 8) death during hospitalization. Platelet counts at presentation to the emergency room (ER) leading to the admissions under study were recorded, as well platelet counts at Baseline. The 56 patients had a median (range) age of 37 (21-66) years; 52% are female, 89% with hemoglobin SS or Sβ 0-thalassemia, and 57% on hydroxyrea (HU). Severe complication occurred in 35 (36%) of the 98 admissions involving 27 (48%) of the patients. Focusing on the first admissions, higher steady-state VWF antigen levels correlated strongly with lower ER platelet counts (ρ= -0.50, P=0.00011, Figure 1A) and higher steady-state ADAMTS13 activity correlated weakly with ER platelet counts (Spearman's ρ= 0.30, P=0.025). The ratio of VWF antigen to ADAMTS13 activity ratio also correlated strongly with lower ER platelet counts (ρ= -0.52, P=0.000052, Figure 1B). In contrast, steady-state VWF antigen level (ρ= -0.17, P=0.23), ADAMTS13 activity (ρ= 0.19, P=0.17), and VWF antigen to ADAMTS13 activity ratio (ρ= -0.23, P=0.098) showed no significant correlation with steady-state platelet counts. The correlations remained by adjusting for age, gender, Hb genotype severity, HU, and treatment of anticoagulant, aspirin, or non-steroidal anti-inflammatory drugs at VOC visits. In analyses restricted to admissions &amp;gt;1 year after Baseline, the correlation between steady-state VWF antigen level and ER platelet counts appeared to persist. Focusing on the 28 first admissions, steady-state VWF antigen level (ρ= -0.50, P=0.0071) and VWF antigen to ADAMTS13 activity ratio (ρ= -0.44, P=0.018) correlated negatively with ER platelet counts. Steady-state ADAMTS13 activity did not correlate with ER platelet counts in admissions that occurred &amp;gt;1 year after Baseline (ρ= 0.16, P=0.43). We further examined the association of steady-state VWF antigen level, ADAMTS13 activity, and their ratio with risk for severe complication in admission. Focusing on the first 56 admissions, which involved 23 complications, steady-state VWF antigen level in the top quartile (1.63) associated with risk for severe complications (OR=6.5, 95% CI 1.4-31, P=0.018, n=56), adjusting for age, gender, Hb genotype severity, and HU. Our observations suggest that steady-state VWF antigen level and the ratio of VWF antigen level to ADAMTS13 activity predict low platelet counts at presentation to VOC admissions, and that steady-state VWF antigen level in SCD patients may be a relatively stable marker for risk of severe VOC complications.

Component-Specific Effects of Team Case Management on Adult Sickle Cell Utilization in Moderate to Low Utilizers

Background: Utilization in adult sickle cell disease (SCD) patients is driven by a large array of biopsychosocial predictors which are often dominated by social determinants of health. We have previously demonstrated that disease management in an Adult Sickle Cell Medical Home may curb avoidable ED visits and hospitalizations, particularly in high utilizers (Blood).[i] However, further analysis is needed to determine the relative “doses” of components, and component-specific effects, of such team interventions as medical care for biological determinants; behavioral health counseling for behavioral determinants; case management for social determinants, and; administrative/reimbursement management for administrative determinants. And further analysis is needed to determine how the latter three, non-biological, components affected total utilization and subtypes of care utilization among moderate to low utilizers within the Medical Home. We examined the latter question for this analysis. The analysis was correlational and non-causal since interventions and outcomes occurred in the same time period. Method: We excluded data available during the “Pre-CoVID” years (2017-2019), in order to isolate impact apart from the COVID phenomenon. We also excluded the 50 Highest utilizers, defined as those with &amp;gt;$200,000 in annual medical charges in a given year and high utilization of the hospital, because they were already assigned specific case managers. Thus, our sample, unlike high-utilization patients, was not assigned specific case managers. We counted and empirically weighted any contact with any member of the Medical Home during a particular year as an intervention. We stacked counts of interventions-multiple visits were weighed more heavily than a single visit. Interventions could have included behavioral health counseling by a licensed clinical social worker. The number of these visits was counted. Case management by Community Health Workers called Patient Navigators (PNs) could have included three types of visits: inpatient, outpatient, and telephone. PN visit weights were obtained by measuring the number of each type of visit, and the time of each visit. Last, prior authorization case management by a reimbursement specialist who was a licensed pharmacy tech each intervention was counted. Thus, the maximum intervention score for any patient in any year was not capped. We calculated charges due to all ambulatory, ED, and hospital utilization separately, and we also calculated combined charges for all utilization. Statistics include Spearman's Correlations, comparing the annual intervention score to charges for each utilization outcome, recognizing that charges would reflect charges for ambulatory medical and behavioral interventions. Results: The sample included N=466 distinct individuals in 2020, 499 in 2021, and 522 in 2022, the “CoVID Years.” Correlations between the annual intervention scores and ambulatory, ED, hospital, and total utilization charges during each corresponding year are shown in Table 1. High PN contact (doses) correlated with more ambulatory visits. More PN contact (dose) was correlated with more inpatient discharges and either more ED visits, or insignificant reductions in ED visits. Conclusion: The case management components of an ambulatory case management program, where patients were not assigned case managers, were inconsistently associated with annual utilization costs for ambulatory care. Because these data were measured essentially simultaneously, we cannot draw causal inferences between management dose and utilization. Perhaps the most significant finding was determining a system of empiric weights for different types of interventions, and summary scores of all interventions may represent a new method to measure team interventions for case management in SCD. [i] Intensive Case Management in an Adult Sickle Cell Medical Home: Annual Effects on Utilization Efficiency Using Community Health Workers; Shirley Johnson, BA, LSW1*, Daniel M Sop, BS, MS2, Yue May Zhang, MS3*,Benjamin Jaworowski, BS 1*and Wally R Smith, MD4

Haploidentical Aß T Cell Depleted HSCT Represents an Alternative Treatment Option in Pediatric and Adult Patients with Sickle Cell Disease (SCD)

Background: Sickle cell disease (SCD) is the most prevalent inherited hemoglobinopathy worldwide, which is associated with considerable morbidity and early mortality. Although HSCT with a MD offers a curative treatment option with an excellent 2-y OS of 95%, availability of MDs is limited and therefore haploidentical HSCT is increasingly explored. Here we update our in vitro T-depleted haploidentical HSCT approach, which is currently explored in a multicenter international trial (NCT04201210). Methods: 29 pts with SCD or SCD-ß Thal (median age: 18 years; range: 2-32) received either a CD3 +/CD19 + (n=9) or aß/CD19 + (n=20) T-haplo-HSCT and were compared with 20 SCD-pts receiving a BM graft from a MSD (median age: 23 years; range: 9-39) at our center. Indication for T-haplo HSCT pts included severe or moderate SCD related complications such as recurrent pain crisis (&amp;gt;5/year), acute chest syndrome, neurological events, osteonecrosis or nephropathy, transfusion-refractory allo-immunization. After exchange transfusion, almost identical conditioning regimens consisting of treosulfan, thiotepa, fludarabine (FTT) and ATG-Grafalon were applied in almost all pts, with the only difference in the timing of ATG (upfront in T-haplo-HSCT, prior to day 0 in MSD-HSCT). Immunosuppression (IST) was maintained for a minimum of 180 days consisting of calcineurin inhibitors (mainly tacrolimus) and MMF. Results: The OS and DFS for MSD and T-haplo-HSCT was 95% and 83%, respectively (Table 1). The median follow-up was 49 months for MSD (range 5-118) and 67 months for T-haplo-HSCT (range 0.5-135). Neutrophil engraftment was achieved after a median of 29 days for MSD pts and 17 days for T-haplo-HSCT with a median of 2.8 x 10 8 TNC/kg (range: 0.65-4.11) and 12 x 10 6 CD3 +/CD19 + or ab/CD19 + depleted CD34 + cells/kg (range: 4.8-49.2), respectively. One pt received two T-haplo HSCT due to primary graft failure after HHV6 infection with effective engraftment after the second transplantation. One pt required a stem cell boost of the same donor with slow subsequent engraftment and one pt died of infectious complications after the fourth T-haplo HSCT. A mixed chimerism &amp;lt;80% was observed in 1/20 MSD-HSCT (median 94.9%; range 40.5-100%) and in 2/29 T-haplo-HSCT pts (median 97.8%; range: 35.7 -100%). No severe cases of &amp;gt;°III aGVD was observed in both populations. MSD pts reached T cell counts &amp;gt;200/µl on day +62 (median; range: 24-293) and T-haplo-HSCT pts on day +136 (median; range: 25-758). Viral reactivation occurred both in T-haplo HSCT (20/29) and in MSD-BMT (9/20). However, one pt in the T-haplo group developed kidney failure after prolonged BKV infection and four of the T-haplo pts died of complications associated with severe CMV or HHV6 infections that were accompanied by hyperinflammation, macrophage activation and acute respiratory distress despite antiviral and anti-inflammatory treatment. One pt of the MSD group died of late treatment related toxicity in combination with preexisting SCD comorbidity. The last fatality occurred in 2020 with now 16 additional pts being transplanted safely, not least also because of a consistent letermovir prophylaxis. Overall, the treosulfan-based conditioning regimen was well tolerated with only one VOD/SOS and one CNS infarction being observed in this high-risk population. 4/20 pts in the MSD group and none in the T-haplo group developed PRES early after conditioning. Conclusions: The safety and efficacy data of this pilot series of T-haplo-HSCT in SCD reveal that T-haplo-HSCT in advanced stage pediatric and adult SCD patients lacking a MSD is feasible. However, diligent viral monitoring and early treatment of viral reactivation, in particular HHV6 is mandatory as otherwise fatal infections may develop.

Antinuclear and Specific Autoantibodies Predict Autoimmune Disease in Sickle Cell Patients: A Longitudinal Cohort Study

Introduction: Sickle cell disease (SCD), the most frequent genetic disorder, can be associated with systemic autoimmune diseases (ADs). High levels of antinuclear antibodies (ANA) are commonly described in SCD, as alloimmunization after blood transfusion. However, the specificity and the prognostic value of ANA have not been fully determined. We aimed to evaluate the association of ANA with AD development during long-term follow-up in SCD patients. Our secondary goal was to assess mortality and serious SCD-related events in this population. Patients and methods: We conducted a single-center longitudinal cohort study on 66 adult SCD patients with ANA titers ≥1/320 at baseline followed over a 13 year-period. Patients known to have an AD (n=9) were excluded from the risk analysis. Results: During follow-up, 13 out of 57 patients (23%) developed AD. Patients with ANA titers ≥1/1280 had a 3-fold increased risk of developing AD (RR 3.4[1.4;8.6]) and a 9-fold increased risk in the presence of specific autoantibodies (anti-DNA, anti-ENA, RF or ACPA) (RR 9.0[3.7;23]) with a positive (PPV) and negative predictive value (NPV) of 90%. When these two immunological features were associated, specificity and PPV reached 100%, with a NPV of 84%. There was no significant difference in the occurrence of serious SCD-related events or mortality rate according to AD. Conclusions: Sickle cell patients with high level of antinuclear antibodies and specific autoantibodies are at high risk of developing AD. The occurrence of AD does not seem to have a significant impact on the course and severity of SCD.

Iron Overload and Treatment Outcome in an Adult Sickle Cell Disease Cohort

Objective. Blood transfusion plays a prominent role in the management of patients with sickle cell disease (SCD) and has a compounded effect on iron overload, especially when simple top-off transfusions are given. Adults with sickle cell anemia (SCA: HbSS or HbSβ 0-thalassemia), often require episodic blood transfusions on a chronic basis and, hence, are at risk of developing transfusional iron overload. We monitored 83 adult SCD patients with a diagnosis of iron overload during routine treatment and follow up at our clinical center. The aim of this study was to observe and describe treatment outcomes for individuals with iron overload seen at the University of Illinois adult sickle cell center between 2010 and 2023. Method. Patients eligible for the study were aged 18 years or above at the time of their initial visit. Patients were identified from our institutional clinical and translational research informatics data warehouse using computable phenotype algorithms as well as SCD outpatient encounter information to improve accuracy of abstracted data. Results of our queries were abstracted in the form of identified patient data and subsequently reviewed in Epic electronic health record (Epic, Verona, WI). We retrospectively studied adult subjects with SCD seen during routine clinical care between 2010 and 2023. Selected subjects had a diagnosis of iron overload, determined by 2 consecutive ferritin levels &amp;gt;1000ng/ml in steady state plus a significant transfusion history. We extracted data on clinical laboratory markers, abdominal imaging, use of iron chelation at baseline and in the final year of follow up, whether patients were receiving chronic erythrapheresis treatment at baseline and at end of follow up, and if alive at the end of the follow up period. Subjects have variable start date and follow up period, beginning at the start of diagnosis of iron overload and ending in June 2023 or last identifiable follow up visit, or mortality. Result. Baseline characteristics of 83 adult patients included in our study are summarized in table 1. Seventy percent of the patients were female and just about everyone had HbSS disease. The females had older median age (39.5year; IQR 32-50 years) than males. The mean ferritin value was significantly higher than the initial measure after a median follows up period of 5.3 years. During the follow up period, 40% of male patients discontinued iron chelation therapy whereas only 5.6% of females did the same. Multivariable analyses were performed for association between change in ferritin measure (between follow up period) with demographic data and other covariates presented in Table 1. Covariates were eliminated by backward selection. Predictors retained in the final model include follow-up period, initial ferritin value, gender, ALT, AST, and albumin. Females had a higher drop in their follow up ferritin, but this was not significant. Neither use of iron chelation therapy at baseline nor erythrapheresis at baseline predicted a change in ferritin value, however we did not collect information on compliance or duration of therapy. Patients followed up for longer duration, or who have higher ALT, had subsequent higher measure for follow up ferritin. Higher albumin predicted a lower ferritin at follow up. The effects of liver markers on ferritin are likely correlative only. After a median follow up period of 5.3years, about 22% of the patients were confirmed to be deceased. Some patients lost to follow up have an indeterminate alive status. Predictors of mortality in multivariate analysis include follow up ferritin value, albumin, and HCV status. Positive HCV status had a strong association with cirrhosis (p=0.001) as 71% of HCV positive individuals had cirrhosis. In turn 53% of the cirrhotic patients died in the follow up period. Conclusion. Here we present an overview of the clinical outcomes of adult patients with SCD and iron overload during a median follow up period of 5.3 years. Despite limitations of a typical retrospective study, our study illustrates the difficulty associated with the management of transfusional iron overload during routine treatment follow up, especially in patients continuing to undergo episodic transfusion treatment. We also continue to underline the low adherence with chelation therapy in adult populations with SCD and iron overload, and the high mortality associated with the condition.

Roxyscan: A Novel Method to Assess Red Blood Cell Resilience to Oxidative Stress in Sickle Cell Disease

Background: Red blood cells (RBCs) are biconcave-shaped cells with viscoelastic membranes that are optimally adapted for oxygen delivery and gas exchange during their normal lifespan of 120 days. Reactive oxygen species (ROS) continuously challenge the viability of RBCs. Despite an arsenal of compounds to protect the RBC, including Glutathione (GSH), Vitamin E, superoxide dismutase (SOD) and Catalase, damage can easily be inflicted that will disrupt cellular deformability, structure, and membrane properties. The susceptibility to oxidative stress in individuals with Sickle Cell Disease (SCD) is believed to be linked to multiple factors. These include the release of heme and iron during hemolysis, inflammation processes, and a reduction in antioxidant defenses. Methods:Susceptibility of RBCs to oxidative stress was assessed with the RoxyScan. This novel application of the Lorrca MaxSis (RR Mechatronics) measures rheological behavior of RBCs in response to cumene hydroperoxide (CuHP, 100 µM) exposure during continuous shear (30 Pa). For this we used the Lorrca's peristaltic pump and suction needle, directing the blood and CuHP to the instrument's cup and mixing them for 30 seconds (s) before starting the run. Deformability of RBCs (EI, elongation index) was measured over time. PoX is defined as the time where a 10% decrease in EI is reached. EI start: EI t=0. EI final: EI t=1600s, ΔEI (EIstart-EIfinal). RoxyScan measurements were performed on blood samples from 16 adult SCD patients (HbSS, HbS/β0 or HbS/β+) and 19 healthy controls (HC). Outcome measurement PoX (calculated from curve fitted data) was correlated to laboratory parameters from complete blood count (Cell Dyn Sapphire, Abbott), RBC sickling tendency (Point of Sickling, PoS, as assessed by oxygen gradient ektacytometry on the Lorrca MaxSis), and levels of HbF/HbS (Tosoh G8). Results:RBCs from untreated HC show a stable EI over time (Fig 1A). Upon exposure to CuHP a similar decrease in EI is seen in 19 HC (Fig 1A), mean decrease 0.055, range (0.017 to 0.10). The mean and median calculated PoX in HC is 1723s and 1702s respectively. In contrast, SCD RBC showed an earlier and more pronounced decrease in EI in response to CuHP exposure (representative example, Fig 1A). Comparing the PoX between HC and SCD revealed significant differences: mean PoX HC: 1723s (SD 329s), SCD: 725s (SD 472s), ***p&amp;lt;0.0001, indicating that SCD RBCs are more susceptible to oxidative stress. Correlating PoX to routine laboratory parameters identified a correlation with Hb levels (***p=0.002), inverse correlation with reticulocyte count (***p=0.0014) and hemoglobin distribution width (HDW, ***p&amp;lt;0.001) (Fig 1B). Similarly strong inverse correlations were found for EI start and EI end (***p&amp;lt;0.001) (Fig 1B). PoX also showed an inverse correlation with red cell distribution width (RDW, ns p=0.07) and mean corpuscular volume (MCV, ns p=0.77). Interestingly, PoX showed a significant inverse correlation with PoS (***p=0.004), indicating that SCD RBCs which are more susceptible to oxidative stress tend to sickle at a higher oxygen tension. PoX showed no significant correlations with HbS/HbF levels (Fig 1B). Conclusion: In this study we demonstrate the applicability of the RoxyScan as a novel method to assess RBC resilience to oxidative stress. When applied to SCD, RBCs show an earlier and more pronounced response to oxidative stress than RBCs from HC. The inverse correlation of PoX, the major outcome parameter of this technique, with reticulocyte count could indicate a generally increased susceptibility to oxidative stress due to a higher level of hemolysis. The correlation with Hb levels affirms this. PoX showed other strong and significant correlations with routine laboratory parameters, such as HDW, implying that the greater variability in hemoglobin content is associated with higher susceptibility to oxidative stress. On a functional level, it is interesting to find strong correlations of PoX with PoS, showing a direct link between RBC sickling tendency and ability to withstand oxidative stress. On the other hand, HbS and HbF levels did not correlate significantly to PoX. Overall, our study highlights the potential use of the RoxyScan and its associated biomarkers in the analysis of the RBC's response to oxidative stress. Further research is in progress to investigate the clinical applicability of this new technique.

Fucosyltransferase VII (FUT7) Activity in Patients with Sickle Cell Disease and Healthy Controls

Background:Sickle cell disease (SCD) is a severe monogenic disorder with a majority of the affected individuals living in Africa. Vaso-occlusion is a significant cause of morbidity and mortality in SCD, and selectin mediated intercellular adhesion is recognized as an important target for therapy. As such Anti-P-selectin agents are in clinical use to reduce the frequency of vaso-occlusive crises (VOCs) in SCD patients. Sialyl lewis x is a crucial ligand common to all members of the selectin family and the final step in the biosynthesis of sialyl lewis X antigen (fucosylation), is catalysed by Fucosyltransferase VII (FUT7). This enzyme is most expressed in leukocytes and endothelial cells. We hypothesized that FUT7 enzyme activity is abnormal in SCD patients and differs by VOC severity. We sought to measure plasma levels of FUT7 in SCD patients and healthy controls, and investigate their association with clinical and laboratory features, such as the frequency of VOCs. Methods:This wasa single centre cross-sectional analytical study at the University of Nigeria Teaching Hospital, Enugu. 38 steady state adult SCD patients and 40 HbAA age- and sex-matched healthy control subjects were enrolled. SCD patients were stratified by clinical severity into: Group A- 19 subjects with mild disease (0-1 crises and no disease complication such as stroke, chronic leg ulcers, nephropathy, or avascular necrosis in the previous year), and Group B- 19 patients with moderate to severe disease (2 or more crises in the previous year, with or without complications). We excluded patients with red cell transfusion within 4 months, on hydroxyurea, or other agents that may affect vaso-occlusive crisis frequency, and co-existing chronic disorders unrelated to SCD, such as asthma and diabetes mellitus. We performed a CBC and plasma FUT7 enzyme concentration measurements (ELISA kit, MyBiosource Inc, USA). Statistical analysis was performed with SPSS version 22.0 for Windows. A 2-tailed P value of &amp;lt;0.05 was used. Results:Our subjects were predominantly female (SCD 52.5%, HbAA 55%), with median age 28 years (range 19-46 and 19-45 for SCD and HbAA, respectively). Median frequency of VOCs in patients was 1 (range 0-5). Avascular necrosis (32.5%) was the most common complication, while stroke, acute chest syndrome, and eye disease were the least common. As expected, SCD patients had lower haemoglobin levels than HbAA (7.9±1.3g/dL vs. 12.6±1.4g/dL, P&amp;lt;0.001). Significantly higher WBC, ANC, and platelet counts were observed in SCD patients compared with HbAA controls (P&amp;lt;0.001). No significant correlations were found between FUT7 and haematocrit (r =0.06), WBC count (r = -0.08), neutrophil count (r = -0.12), and platelet count (r =0.1), with P values of 0.7, 0.6, 0.5, and 0.6, respectively. We found no difference between the median and IQR values of plasma FUT7 of SCD (2.1; 1.8-2.5) and controls (2.2; 1.8-2.8), P = 0.7. FUT7 activity was higher in SCD subjects in Group A (2.2; 1.9-2.9) than in Group B (2.0; 1.2- 2.4), with a trend towards significance P = 0.1. Discussion:In this study, FUT7 activity did not differ between SCD patients and controls. We also did not find correlations between FUT7 and blood cell counts, suggesting that plasma FUT7 activity is not increased at baseline in SCD and that the degrees of anemia or leukocytosis are not associated with changes in FUT7. Nonetheless, a mild decrease in FUT7 levels was found in more severe SCD patients and should be confirmed in a larger study. Our study did not evaluate patients in crises or who received hydroxyurea and/or other SCD-modifying therapies. Since FUT7 catalyses selectin expression, variation in its activity may be more relevant in subgroups of SCD patients on anti-selectin therapies. Future studies should be carried out in such patients to explore FUT7 activity as a marker of acute vaso-occlusion and as a modifier of response to therapy.

Insights on Sickle Cell Disease Therapies in Sierra Leone

Introduction: Ongoing sickle cell disease (SCD) gene therapy clinical trials in the United States and other high resource countries have shown promising results, and several therapies are under U.S. Food and Drug Administration review in 2023. Despite these advances, the current evidence-based practices are not accessible to much of the world's sickle cell population. As treatment advances are made for SCD, the integration of these therapies in sub-Saharan African countries-which have the highest prevalence of SCD-requires a global partnership. Sierra Leone ranks 9 th in burden in sub-Saharan Africa with annual SCD births between 4000-5000. Efforts are underway in Sierra Leone to improve awareness and healthcare infrastructure for the SCD population; however, the country still lacks a national screening program for diagnosis and faces challenges in providing comprehensive care across the lifespan. This study examines adult SCD patients' knowledge of current evidence-based care and novel gene therapies in Sierra Leone. Methods: In 2021-2022, a cohort (n=123) of adults living with SCD in Sierra Leone were surveyed as part of the INSIGHTS Study (NCT02156102). A mixed-methods recruitment strategy was used, including via public service announcements hosted on local radio stations, information disseminated via a WhatsApp group, and snowball sampling. Recruitment was conducted in two settings, one urban (Freetown) and one rural (Kono). Participants completed this cross-sectional study from September 2021-February 2022. Questions were asked regarding participants' perspectives and knowledge of hydroxyurea, the current standard of care treatment for SCD, and novel experimental gene therapy. Results: The mean age of respondents was 23.6 years (range 18-63). The majority of respondents were female (65.6%), educated at or above the senior secondary school level (78.7%), and students (70.3%). Respondents predominantly had the HbSS genotype (89.4%). Most study participants lacked awareness of hydroxyurea and gene therapy (93.5% had never heard of hydroxyurea; 95.1% had never taken hydroxyurea; 94.8% had never heard of gene therapy for SCD treatment) (Table 1). Despite this gap in knowledge, the majority (95.0%) agreed that genetic research is a necessary way to learn about treatments for SCD (Table 1). Discussion: Our results highlight disparities in current standard of care treatment and knowledge in a country with a high prevalence of SCD. While our cohort indicated a favorable attitude toward SCD research and a willingness to participate, these results highlight a significant barrier for successful implementation of current treatment and the adoption of curative genetic therapies in limited resource settings like Sierra Leone. Given the significant lack of knowledge around hydroxyurea, it is important that public health initiatives and research should be directed toward both established standard of care and creating awareness of experimental therapies.