The use of hydroxyurea for the prevention of sickle cell crises in
patients with homozygous HbS disease is now well established. The
beneficial effects of this compound stem from (a) selective enrichment
of red cells containing an increased amount of fetal hemoglobin, which
inhibits HbS polymerization, and (b) a decrease of leukocytes,
platelets, and reticulocytes, which significantly limits their adherence
to the vascular wall. We report the results of a clinical trial of
hydroxyurea on 55 Greek-origin patients with sickle cell/beta
-thalassemia and 14 patients with homozygous HbS disease who have been
treated with hydroxyurea for several years. Such patients have a higher
probability to benefit from hydroxyurea therapy, since in addition to
its antisickling effect, the increase of gamma -chain synthesis is
expected to diminish the deleterious effects of the unbound alpha
-globin chains. Selection of patients and monitoring throughout the
whole trial were done by the same clinicians. Quantitative expression of
the clinical condition was done using a system scoring several outcome
parameters. For a period of 52 months prior to starting treatment, the
total score of severity for 59 evaluable patients was 1182 points (3068
patient-weeks), while for the 12,018 patient-weeks of the trial this
parameter fell to only 82 points. Other observations of interest include
the significant improvement of a group of patients with hepatic
cholestasis, the development of leg ulcers possibly related to the
treatment, and the dramatic increase of hemoglobin F, often in
association with an increase of the total hemoglobin levels as a result
of decreased hemolysis. (C) 2000 Academic Press
