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Effects of hydroxyurea on hemoglobin F and water content in the red blood
cells of dogs and of patients with sickle cell anemia
EP Orringer, DS Blythe, AE Johnson, G Phillips , GJ Dover and JC Parker
Department of Medicine, University of North Carolina at Chapel Hill
27599-7600.
A rationale for clinical trials of hydroxyurea (HU) treatment in sickle
cell disease is that the agent increases red blood cell (RBC) fetal
hemoglobin content. However, an additional effect of HU is to raise the
mean corpuscular volume (MCV). To investigate the action of HU in a species
that makes no electrophoretically distinguishable fetal hemoglobin, we
treated dogs with the drug and compared their response to that of five
patients with sickle cell anemia. Both dogs and patients had an increase in
MCV, but the effect of HU treatment on the mean corpuscular hemoglobin
concentration (MCHC), density, and water content of the RBCs differed in
the two species. The dog RBCs became low in MCHC, high in ion and water
content, and low in mean density. Thus, HU can raise MCV and lower MCHC
without influencing fetal hemoglobin synthesis. A different pattern was
seen in the sickle cell patients during HU treatment. Although the MCV of
their RBCs increased, there was no change in MCHC, ion content, or mean
density. A notable change in the sickle cell patients' blood was that two
subpopulations of cells were nearly eliminated during HU treatment; the
hypodense reticulocyte fraction and the hyperdense fraction that contains
irreversibly sickled cells. These findings lead us to suggest that trials
of HU in sickle cell disease must recognize the possibility that any
beneficial effect of this agent might be due not only to an increase in
hemoglobin F alone, but perhaps also to the associated increase in MCV or
the altered RBC density profile.
Volume 78,
Issue 1,
pp. 212-216,
07/01/1991
Copyright © 1991 by The American Society of Hematology
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