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A multiparameter analysis of sickle erythrocytes in patients undergoing
hydroxyurea therapy
KR Bridges, GD Barabino, C Brugnara, MR Cho, GW Christoph, G Dover, BM Ewenstein, DE Golan, CR Guttmann, J Hofrichter, RV Mulkern, B Zhang and WA Eaton
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115,
USA.
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 umbilical vein
endothelial cells in a laminar flow chamber, RBC phthalate density
profiles, mean corpuscular hemoglobin concentration and cation content,
reticulocyte mean corpuscular hemoglobin concentration, 1H-nuclear magnetic
resonance transverse relaxation rates of packed RBCs, and plasma membrane
lateral and rotational mobilities of band 3 and glycophorins. Hydroxyurea
increases the fraction of cells with sufficiently long delay times to
escape the microcirculation before polymerization begins. Furthermore, high
pretreatment adherence to human umbilical vein endothelial cells of sickle
RBCs decreased to normal after only 2 weeks of hydroxyurea treatment,
preceding the increase in fetal hemoglobin levels. The lower adhesion of
sickle RBCs to endothelium would facilitate escape from the
microcirculation before polymerization begins. Hydroxyurea shifted several
biochemical and biophysical parameters of sickle erythrocytes toward values
observed with hemoglobin SC disease, suggesting that hydroxyurea moderates
sickle cell disease toward the milder, but still clinically significant,
hemoglobin SC disease. The 50% reduction in sickle crises documented in the
Multicenter Study of Hydroxyurea in Sickle Cell Disease is consistent with
this degree of erythrocyte improvement.
Volume 88,
Issue 12,
pp. 4701-4710,
12/15/1996
Copyright © 1996 by The American Society of Hematology
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