Sickle cell disease is characterized by intraerythrocytic hemoglobin S polymerization that leads to vasoocclusive events and chronic hemolytic anemia. Hemolysis, although traditionally considered simply a cause of anemia and gallstone formation, has been shown to cause endothelial dysfunction and chronic vascular injury via the release of cell free plasma hemoglobin and arginase 1, which collectively reduce nitric oxide (NO) bioavailability and enhance reactive oxygen species (ROS) formation. 2, 3 Oxidation of hemoglobin can result in the release of free heme into plasma, which in excess has recently been shown to activate Toll-like receptor 4 (TLR4) and promote vasoocclusion and acute lung injury. 4, 5