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.