The modern use of hydroxyurea for children with sickle cell anemia
Over the past 40 years, the introduction and refinement of hydroxyurea therapy has led to remarkable progress in the care of individuals with sickle cell anemia (SCA). From initial small proof-of-principle studies to multicenter phase III controlled clinical trials and then numerous open-label studies, the consistent benefits of once-daily oral hydroxyurea have been demonstrated across the lifespan. Elevated fetal hemoglobin (HbF) serves as the most important treatment response, as HbF delays sickle hemoglobin polymerization and reduces erythrocyte sickling. Increased amounts of HbF, especially when distributed across the majority of erythrocytes, improve clinical outcomes by reducing hemolytic anemia and preventing vaso-occlusion, thereby ameliorating both acute and chronic – and overt and covert – complications. Additional benefits of hydroxyurea beyond HbF induction include lower neutrophil and platelet counts, reduced inflammation, and improved rheology. Toxicities of hydroxyurea i
