Fetal Hemoglobin is Associated with Peripheral Oxygen Saturation in Sickle Cell Disease in Tanzania

Fetal hemoglobin (HbF) and peripheral hemoglobin oxygen saturation (SpO₂) both predict clinical severity in sickle cell disease (SCD), while reticulocytosis is associated with vasculopathy, but there are few data on mechanisms. HbF, SpO₂ and routine clinical and laboratory measures were available in a Tanzanian cohort of 1175 SCD individuals aged≥5years and the association with SpO₂ (as response variable transformed to a Poisson distribution) was assessed by negative binomial model with age and sex as covariates. Increase in HbF was associated with increased SpO₂ (rate ratio, RR=1.19; 95% confidence intervals [CI] 1.04, 1.37 per natural log unit of HbF; p=0.0004). In univariable analysis, SpO₂ was inversely associated with age, reticulocyte count, and log (total bilirubin) and directly with pulse, SBP, hemoglobin, and log(HbF). In multivariable regression log(HbF) (RR 1.191; 95%CI 1.04, 1.37; p=0.013), pulse (RR 1.01; 95%CI 1.00, 1.01; p=0.026), SBP (RR 1.008; 95%CI 1.00, 1.02; p=0.014), and hemoglobin (1.120; 95%CI 1.05, 1.19; p=0.001) were positively and independently associated with SpO₂ while reticulocyte count (RR 0.985; 95%CI 0.97, 0.99; p=0.019) was independently inversely associated with SpO₂. In SCD, improving SpO₂, in part through cardiovascular compensation and associated with reduced reticulocytosis, may be a mechanism by which HbF reduces disease severity.