Determinants of Red Cell Survival and Erythropoietic Activity in Patients with Sickle Cell Anemia in the Steady State

Abstract

We have studied 26 patients with sickle cell anemia to determine the factors that affect red blood cell (RBC) survival and other parameters of erythropoietic activity in the steady state. Determinants of erythropoietic activity included RBC survival by the ⁵¹Cr method, RBC production/destruction rate, a genotype, β^s haplotype, plasma ⁵⁹Fe clearance, plasma iron turnover, eryth-ron transferrin uptake), RBC Fe utilization, reticulocyte count, and erythro-poietin levels. The α genotype was the most significant determinant of RBC survival followed, to a lesser extent, by the β^s haplotype. Hb F showed no correlation with RBC survival due to patient selection bias - the patients studied had comparable Hb F levels to start with. Other determinants of erythropoietic activity (hemoglobin level, mean corpuscular volume, reticulocyte count, RBC mass, RBC production/destruction rate, and erythropoietin level) were most likely secondary determinants associated with the α genotype, and not independent determinants in themselves. The data suggest that the α genotype and, and to a lesser extent, the β^s haplotype, might be determinants of the severity of the anemia of sickle cell disease, and should be considered in genetic counseling and patient selection for aggressive therapeutic interventions.