Multiple beneficial effects of hydroxyurea for SCA. (1) Fetal hemoglobin induction through soluble guanylyl cyclase activation and altered erythroid kinetics; (2) lower neutrophil and reticulocyte counts from ribonucleotide reductase inhibition and marrow cytotoxicity; (3) decreased adhesiveness and improved rheology of circulating neutrophils and reticulocytes; (4) reduced hemolysis through improved erythrocyte hydration, macrocytosis, and reduced intracellular sickling; and (5) Nitric oxide (NO) release with potential local vasodilatation and improved vascular response. Illustration courtesy of Alice Y. Chen.