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

<jats:p>Low hemoglobin oxygen saturation (SpO<jats:sub>2</jats:sub>) 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<jats:sub>2</jats:sub>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<jats:sub>2</jats:sub>was 97% (IQ range 94–99%) in SCA (<jats:italic>N</jats:italic>= 458), lower () than non-SCA (median 99%, IQ range 98–100%;<jats:italic>N</jats:italic>= 394). Within SCA, associations with SpO<jats:sub>2</jats:sub>were observed for hematological variables, transferrin saturation, body-mass-index<jats:italic>z</jats:italic>-score, hemoglobin F (HbF%), genotypes, and hemolytic markers; mean cell hemoglobin (MCH) explained most variability (, Adj ). In non-SCA only age correlated with SpO<jats:sub>2</jats:sub>. -thalassemia 3.7 deletion highly correlated with decreased MCH (Pearson correlation coefficient 0.60, ). In multivariable models, lower SpO<jats:sub>2</jats:sub>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<jats:sub>2</jats:sub>in children with SCA. Potential mechanisms and implications are discussed.</jats:p>