A MULTIPARAMETER ANALYSIS OF SICKLE ERYTHROCYTES IN PATIENTS UNDERGOING HYDROXYUREA THERAPY

During 24 weeks of hydroxyurea treatment, we monitored red blood cell (RBC) parameters in three patients with sickle cell disease, including F-cell and F-reticulocyte profiles, distributions of delay times for intracellular polymerization, sickle erythrocyte adherence to human um bilical vein endothelial cells in a laminar flow chamber, RBC phthalat e density profiles, mean corpuscular hemoglobin concentration and cati on content, reticulocyte mean corpuscular hemoglobin concentration, H- 1-nuclear magnetic resonance transverse relaxation rates of packed RBC s, and plasma membrane lateral and rotational mobilities of band 3 and glycophorins. Hydroxyurea increases the fraction of cells with suffic iently long delay times to escape the microcirculation before polymeri zation begins. Furthermore, high pretreatment adherence to human umbil ical vein endothelial cells of sickle RBCs decreased to normal after o nly 2 weeks of hydroxyurea treatment, preceding the increase in fetal hemoglobin levels. The lower adhesion of sickle RBCs to endothelium wo uld facilitate escape from the microcirculation before polymerization begins. Hydroxyurea shifted several biochemical and biophysical parame ters of sickle erythrocytes toward values observed with hemoglobin SC disease, suggesting that hydroxyurea moderates sickle cell disease tow ard the milder, but still clinically significant, hemoglobin SC diseas e. The 50% reduction in sickle crises documented in the Multicenter St udy of Hydroxyurea in Sickle Cell Disease is consistent with this degr ee of erythrocyte improvement. This is a US government work. There are no restrictions on its use.