Hematological and Genetic Predictors of Daytime Hemoglobin Saturation in Tanzanian Children with and without Sickle Cell Anemia

Low hemoglobin oxygen saturation (SpO(2)) is common in Sickle Cell Anemia (SCA) and associated with complications including stroke, although determinants remain unknown. We investigated potential hematological, genetic, and nutritional predictors of daytime SpO(2) in Tanzanian children with SCA and compared them with non-SCA controls. Steady-state resting pulse oximetry, full blood count, transferrin saturation, and clinical chemistry were measured. Median daytime SpO(2) was 97% (IQ range 94–99%) in SCA (N = 458), lower (P < 0.0001) than non-SCA (median 99%, IQ range 98–100%; N = 394). Within SCA, associations with SpO(2) were observed for hematological variables, transferrin saturation, body-mass-index z-score, hemoglobin F (HbF%), genotypes, and hemolytic markers; mean cell hemoglobin (MCH) explained most variability (P < 0.001, Adj r (2) = 0.09). In non-SCA only age correlated with SpO(2). α-thalassemia 3.7 deletion highly correlated with decreased MCH (Pearson correlation coefficient −0.60, P < 0.0001). In multivariable models, lower SpO(2) correlated with higher MCH (β-coefficient −0.32, P < 0.001) or with decreased copies of α-thalassemia 3.7 deletion (β-coefficient 1.1, P < 0.001), and independently in both models with lower HbF% (β-coefficient 0.15, P < 0.001) and Glucose-6-Phosphate Dehydrogenase genotype (β-coefficient −1.12, P = 0.012). This study provides evidence to support the hypothesis that effects on red cell rheology are important in determining SpO(2) in children with SCA. Potential mechanisms and implications are discussed.