Most Adults with Severe HbSC Disease are not Treated with Hydroxyurea.

HbSC disease is the second most frequent sickle cell disease (SCD) genotype after HbSS. Globally, approximately 55,000 newborns are delivered annually with HbSC disease, with the highest HbC gene frequency in West Africa. In Ghana, 40% of adults attending the Ghana Institute of Clinical Genetics SCD clinic have HbSC. Unlike HbSS, hydroxyurea is not routinely recommended for use in individuals with HbSC disease because of the perceived high risk benefit ratio. To test the hypothesis that at least 5% of adults with HbSC will meet the American Society of Hematology (ASH) criteria for severe disease, we conducted a retrospective descriptive cohort study of all individuals with HbSC (≥18 years) who attended the clinic in 2019 (N=1,018). HbSC adults ages 18-45 years were then selected (n=639). We identified a comparison group of 639 individuals with HbSS, frequency matched by age and gender to the individuals with HbSC. Severe disease was defined as a history of ≥ 3 SCD-associated moderate to severe pain episodes/year, a history of acute chest syndrome, and severe symptomatic chronic anemia that interferes with daily activities or quality of life. Study endpoints were the proportion of individuals with SCD who met the definition of severe disease and were eligible for hydroxyurea. In total, 10.0% (64/639) of individuals with HbSC met the eligibility criteria for hydroxyurea therapy, compared to 24.1% (154/639) of individuals with HbSS, p<0.001. Less than 1% and 3% of individuals with severe HbSC and HbSS, respectively, are routinely prescribed hydroxyurea in this tertiary care medical center.