Nkya S
Mgaya J
Urio F
Makubi A
Thein SL
Menzel S
Cox SE
Newton CR
Kirkham FJ
Mmbando BP
Makani J
EBioMedicine. 2017;23146-149
Fetal hemoglobin (HbF) and peripheral hemoglobin oxygen saturation (SpO(2)) both predict clinical severity in sickle cell disease (SCD), while reticulocytosis is associated with vasculopathy, but there are few data on mechanisms. HbF, SpO(2) and routine clinical and laboratory measures were available in a Tanzanian cohort of 1175 SCD individuals aged>/=5years and the association with SpO(2) (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 SpO(2) (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, SpO(2) 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 SpO(2) while reticulocyte count (RR 0.985; 95%CI 0.97, 0.99; p=0.019) was independently inversely associated with SpO(2). In SCD, improving SpO(2), in part through cardiovascular compensation and associated with reduced reticulocytosis, may be a mechanism by which HbF reduces disease severity.
