Children with HbSβ0 thalassemia have higher hemoglobin levels and lower incidence rate of acute chest syndrome compared to children with HbSS.

Abstract

Based on the presumed clinical similarity between the two most severe sickle cell disease (SCD) genotypes, hemoglobin (Hb) Sβ0 thalassemia and HbSS, randomized controlled trials (RCTs) have included both genotypes. Our group has demonstrated that healthcare providers inadequately distinguish the two diagnoses through clinical and laboratory parameters. In a retrospective cohort study utilizing data from the Silent Cerebral Infarct Transfusion trial (NCT00072761), we tested the hypothesis that children with genotypic diagnoses of HbSβ0 thalassemia, when compared to HbSS, have significantly different rates of SCD comorbidities. Exclusion criteria included those with previous overt stroke or treatment with hydroxyurea or regular blood transfusion therapy. Among children with HbSβ0 thalassemia (n=22) and HbSS (n=786), the mean hemoglobin was higher in children with HbSβ0 thalassemia (9.2g/dl) compared to HbSS (8.1g/dl, P<0.001). In children with HbSβ0 thalassemia, when compared to HbSS, the incidence rate of acute chest syndrome (ACS) was 3.0 and 14.4 events per 100 patient-years (P=0.028), and mean transcranial Doppler (TCD) velocities were 112.6 and 135.6cm/sec, respectively (P=0.026). The number of children with HbSβ0 thalassemia and HbSS with conditional TCD velocities were zero (0%) and 26 (4.9%), respectively (P=1.00), and the number with silent cerebral infarcts were five (27.8%) and 209 (30.8%), respectively (P=0.78). We have provided preliminary evidence that clinically relevant differences occur in ACS rates and TCD velocities between children with HbSβ0 thalassemia and HbSS. Future SCD RCTs should consider balanced allocation of these SCD genotypes, particularly when ACS and abnormal TCD velocities are primary outcome measures.