Mitochondrial therapeutics. Red cell hemolysis produces cell-free hemoglobin and heme, which leads to NO scavenging, formation of ROS, and platelet activation. Red cells also release ADP, which activates platelets and arginase, decreasing NO bioavailability (not shown). Hemoglobin leads to decreased platelet mitochondrial complex V activity and oxidative stress. Arginine therapy improves mitochondrial function in sickle cell patients, but whether the mechanism involves direct inhibition of platelet activation by NO, countering the deleterious effects of hemoglobin/heme, transiently modulating platelet complex I, or by  limiting systemic-ischemia-reperfusion stress remains to be determined. Professional illustration by Patrick Lane, ScEYEnce Studios.