Mechanisms of action of hydroxyurea.

Hydroxyurea acts on the bone marrow and, by its cytotoxic effects, selects a population of erythroblasts that can synthesize increased amounts of HbF. It has no known direct effects on gene expression. Bone marrow cellularity may also be diminished (left). Higher concentrations of HbF reduce the level of HbS polymer and the numbers of deformed, dense, and damaged erythrocytes. Cells with a high HbF content survive longer, attenuating hemolysis and leading to a reduction in reticulocytes. Circulating granulocytes, monocytes, and platelets are diminished (center). Fewer dense, poorly adhesive erythrocytes are less apt to adhere to and perturb the endothelium, reducing the likelihood of vasoocclusion (right).¹²⁵