Most adults with severe HbSC disease are not treated with hydroxyurea

Abstract

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.

Systemic medications for sickle cell disease and potential applications for sickle cell retinopathy

“…Of note, hydroxyurea is not routinely recommended for patients with HbSC disease, even those with severe disease, these patients may have milder systemic disease manifestations. Further, hydroxyurea has not been formally evaluated in HbSC patients [12 ▪ ]. Given that proliferative sickle cell retinopathy has been shown to be more common in patients with HbSC disease and is by far the most common cause of vision loss in individuals with SCD, future studies are necessary to determine the efficacy of hydroxyurea in patients with HbSC disease.…”

Seeing haemoglobin SC: Challenging the misperceptions

“…A retrospective review of 639 participant records from the Ghana Institute of Clinical Genetics, the largest SCD clinic in Ghana found that about 10% of adolescents and adults with HbSC disease had severe SCD, using the American Society of Hematology criteria, and yet 99% of those with severe disease were not on any form of diseasemodifying therapy. 7 While this may have been contextual, driven by the availability, acceptability and affordability of disease-modifying therapies in Ghana, it magnifies the disparities in disease management between SCD genotypes. Not only are there missed opportunities to manage HbSC disease effectively, but many knowledge gaps also remain.…”

It’s high time to turn the spotlight on HbSC disease

“…Ghunney et al 1 also show us that the prevalence of HbSC disease is higher in Ghana (40%) than in the US (30%), which further underscores the urgency of addressing important questions on the options for disease-modifying therapy for this large population of patients. Interestingly, the prevalence of some HbSC comorbidities in the study by Ghunney et al (see figure ) is lower than reported in prior studies in higher-income countries 9 ; this could be a result of survival bias because many children with severe complications die before reaching adulthood in Ghana owing to a lack of early diagnosis and adoption of preventive interventions.…”

“…In this issue of Blood Advances , the study by Ghunney et al 1 sheds light on the prevalence and severity of HbSC disease, the second most common variant of sickle cell disease (SCD), in a large cohort of patients with SCD at the Ghana Institute of Clinical Genetics SCD Clinic. The authors find that about 10.5% and 24.1% of individuals with HbSC and HbSS, respectively, were eligible for initiation of hydroxyurea based on disease severity; unfortunately, of those, less than 3% and 1%, respectively, were prescribed the drug.…”