Figure 1. Mechanisms of hemolytic anemia in reducing NO bioavailability and association with vasculopathic sub-phenotypes of sickle cell disease.
Hemolysis releases cell-free plasma hemoglobin and arginase 1 into plasma, which catabolize NO and L-arginine. Activation of vascular oxidases, such as xanthine oxidase, NADPH oxidase and uncoupled eNOS, generate superoxide which scavenges NO. Hemolytic anemia and reduced NO bioavailability are associated with vasculopathic clinical complications in SCD patients.