Purpose: Pulmonary hypertension (PH) is a chronic complications of sickle cell disease (SCD) with limited known biomarkers, beyond increases in plasma brain natriuretic peptide levels. Experimental Design: We conducted a proof-of-concept study to identify serum protein biomarkers that were differentially expressed in SCD patients with elevated tricuspid regurgitation velocity (TRV – a noninvasive marker of PH). Results: We found 41 out of 92 target proteins that were significantly different between the non-elevated (TRV≤2.6 m/sec; N = 35) and highly elevated TRV group (TRV≥2.9 m/sec; N = 35, p<0.05). Six of them passed a Bonferroni correction (p value < 0.0005) including T-cell surface glycoprotein, lymphotactin, SLAM family member 7, galectin-9, TNF-related apoptosis-inducing ligand receptor 2, and tumor necrosis factor receptor superfamily member 11A . We observed up to a 1.2-fold increase in the high TRV group for these six proteins. These six proteins had strong positive correlation with serum NT-proBNP levels (a positive control marker elevated in PH (r >= 0.44). Additionally, these markers correlated with other clinical parameters of PH in SCD. Conclusion: Circulatory protein markers of the immune response are increased in SCD patients with elevated TRV as compared to those without elevated TRV.

Background: Sickle cell disease (SCD) is one of the most common inherited red blood cell disorders in the world, and the vast majority of infants born with SCD are from Sub-Saharan Africa (SSA). Recent studies have definitively established that hydroxyurea is safe and highly effective for children with SCD in SSA. However, there is a lack of data on the long-term outcomes for children with SCD in SSA beyond early childhood. Procedure: We conducted a retrospective analysis of AYA SCD patients ≥16 yo who received care in a pediatric SCD clinic in Malawi between January 2015 and December 31, 2022 Results: We identified 207 patients ≥16 yo in the SCD clinic electronic database. The vast majority (195, 94%) were alive and receiving care in the pediatric SCD clinic. Three patients had died, and 9 were lost to follow-up. The mean age of patients alive and receiving care was 18±1.9 yo. The mean age at diagnosis was 5.7±1.1 yo. Nearly all AYA patients (N=187, 96%) were taking hydroxyurea for a mean duration of 6±2.7 years. Mean baseline laboratory values were: hemoglobin 8.0±1.3 g/dL, mean corpuscular volume 92±8.4 fl, white blood count 14.2±7.0 × 10 3 /µL, absolute neutrophil count (ANC) 6.2±4.8 × 10 3 /µL, and platelets 343±167 × 10 3 /µL. Among all patients, 21% had at least one transfusion, and 23% of patients had been hospitalized at least once for sickle cell-related complications. Conclusion: We provide the first description of an AYA cohort with SCD receiving routine care with hydroxyurea in a dedicated pediatric clinic under real-world conditions. This study highlights hydroxyurea’s long-term feasibility and underscores the need to enhance the capacity for comprehensive adult care, especially in SSA’s rapidly expanding AYA population.