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BackgroundComprehensive care in homozygous sickle cell disease (HbSS) entails universal neonatal screening and subsequent monitoring of identified patients, a process which has been streamlined in the neighbouring island of Jamaica. In preparation for a similar undertaking in Barbados, we have developed a database of persons with known HbSS, and have piloted processes for documenting clinical manifestations. We now present a brief clinical profile of these findings with comparisons to the Jamaican cohort.MethodsHbSS participants were recruited from clinics and support groups. A history of select clinical symptoms was taken and blood and urine samples and echocardiograms were analysed. A re-analysis of data from a previous birth cohort was completed.ResultsForty-eight persons participated (32 F/16 M); age range 10–62 yrs. 94% had a history of ever having a painful crisis. In the past year, 44% of participants had at least one crisis. There were >69 crises in 21 individuals; 61% were self-managed at home and the majority of the others were treated and discharged from hospital; few were admitted. The prevalence of chronic leg ulceration was 27%. Forty-two persons had urinalysis, 44% were diagnosed with albuminuria (urinary protein/creatinine ratio ≥30 mg/g). Thirty-two participants had echocardiography, 28% had a TRJV ≥ 2.5 m/s. Re-analysis of the incidence study revealed a sickle gene frequency (95% CI) of 2.01% (0.24 to 7.21).ConclusionAlthough we share a common ancestry, it is thought that HbSS is less common and less severe in Barbados compared to Jamaica. The Jamaican studies reported a sickle gene frequency of 3.15 (2.81 to 3.52); the prevalence of chronic leg ulcers and albuminuria was 29.5% and 42.5% respectively. These comparisons suggest that our initial thoughts may be speculative and that HbSS may be an underestimated clinical problem in Barbados. A prospective neonatal screening programme combined with centralized, routine monitoring of HbSS morbidity and outcomes will definitively answer this question and will improve the evidence-based care and management of HbSS in Barbados.

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Objectives Following intravascular hemolysis, free hemoglobin A is bound to haptoglobin (Hp), internalized by monocytes bearing the hemoglobin scavenger receptor, CD163, and broken down via the heme-oxygenase (HO)-1 enzyme into the cytoprotective metabolites biliverdin and carbon monoxide. This triggers an IL10 positive feedback loop which augments CD163 expression; thereby increasing hemoglobin scavenging capacity and limiting the vascular insult caused by oxidative free heme. During iatrogenic hemolysis caused by cardiopulmonary bypass, we have demonstrated that serum Hp is temporarily consumed while the surface CD163 and HO-1 expression is up-regulated. In homozygous sickle cell disease (HbSS), chronic hemolysis is linked with exhaustion of serum Hp and suppression of CD163 compared to HbAA controls. Our objective was to determine if the extent of Hp depletion correlates with the CD163 suppression and with select clinical features within the Barbadian HbSS population. Design & Methods Persons with HbSS were referred from private and public hematology clinics and support groups. Exclusion criteria were blood transfusion in the last three months, a sickle crisis in the last month and the use of oral corticosteroids, since these may affect CD163 expression. A history of painful crises, leg ulcers, renal compromise and pulmonary hypertension was ascertained. Urine samples were analyzed for albumin:creatinine ratio and echocardiograms were analyzed for the tricuspid regurgitant jet velocity (TRJV). Whole blood was collected in EDTA and analyzed by two color flow cytometry for the mean fluorescent intensity (MFI) of CD163 expression on gated CD14+ monocytes. Plasma Hp was analyzed by ELISA. The association between Hp concentration and CD163 was analyzed using median regression. The effect of Hp concentration on clinical outcome was explored using logistic regression, adjusting for the effects of age, sex, and total hemoglobin. Results Forty-eight persons with HbSS participated. Forty-seven percent of participants had at least one painful crisis in the past year and 28% of participants had a history of chronic leg ulceration. Forty-one persons had urinalysis, of these 44% of persons were diagnosed with renal compromise as defined by a urinary protein/creatinine ratio of >30mg/g; at least 15% had macro-albuminuria (urinary protein/creatinine ratio of >300mg/g). Thirty-two participants had echocardiograms, 19% indicated pulmonary hypertension (pHTN) as defined by a TRJV ≥ 2.5m/s. The mean (95% CI) Hp concentration was 4 (3.2 to 4.8) [reference range in HbAA 41-165mg/dl]. Linear regression showed that for every 1mg/dl increase in Hp concentration, CD163 MFI increased by 0.17 (95% CI 0.05 – 0.3) p=0.01 (Figure 1). For every 1mg/dl decrease in Hp levels; the odds of reporting a pain crisis in the last year increase by 1.38 (95%CI 0.84 to 2.27) p=0.2; the odds of having renal compromise increase by 3.56 (1.19 to 10.7) p=0.02 and the odds of reporting a history of leg ulcer increase by 1.33 (0.71 to 2.49) p=0.37 (Figure 2). For every 1mg/dl decrease in Hp, the TRJV increases by 0.10 (-0.15 to 0.34) p=0.36. Conclusion Depletion of serum Hp correlates with diminished CD163 expression and with increasing severity of clinical features in HbSS. This suggests that the fault in the hemoglobin scavenging apparatus is probably due to chronic depletion of Hp. Replacement of Hp may therefore be a viable therapeutic prospect aimed at restoring the positive feedback loop and conferring vascular protection. Disclosures: No relevant conflicts of interest to declare.