Pathophysiological-based approaches to treatment of sickle cell disease.

Sickle hemoglobin (HbS), as a result of its polymer-related and oxidant effects, damages the sickle erythrocyte, provokes inflammation, and causes endothelial injury. All these elements cause the phenotype of sickle cell disease. Novel treatments inhibit HbS polymerization by inducing fetal hemoglobin expression, prevent or repair erythrocyte dehydration by slowing cellular potassium and water loss, and replace HbS-producing erythroid progenitors by stem cell transplantation. Future treatment prospects include gene therapy, interruption of the interaction of sickle cells with the endothelium, inhibition of oxidative damage, and protection of an injured endothelium.