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

Abstract

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 () 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 (, Adj ). In non-SCA only age correlated with SpO 2 . -thalassemia 3.7 deletion highly correlated with decreased MCH (Pearson correlation coefficient 0.60, ). In multivariable models, lower SpO 2 correlated with higher MCH (-coefficient 0.32, ) or with decreased copies of -thalassemia 3.7 deletion (-coefficient 1.1, ), and independently in both models with lower HbF% (-coefficient 0.15, ) and Glucose-6-Phosphate Dehydrogenase genotype (-coefficient 1.12, ). 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.