Hemoglobin Mediated Regulation of Platelet Functions - Abstract
In patients of hemolytic disorders, presence of excessive free hemoglobin (Hb) in plasma causes several cytotoxic effects. Hb being a potent scavenger of nitric oxide (NO) impairs the NO-mediated vasodilatory functions, thus promoting blood vessel constriction and related clinical events in hemolytic patients. This decrease in endogenous level of NO, an inhibitor of platelet activation, increases thrombophilic complications in these patients. Hb also generates reactive oxygen species (ROS) and affects several cellular functions. Hypercoagulation, thrombosis and inflammation are
hallmark features of hemolytic disorders like sickle cell disease (SCD), paroxysmal nocturnal hemoglobinuria (PNH), thalassemia, hemolytic uremic syndrome (HUS) and Aplastic anemia (AA). We have recently described a novel mechanism of Hb mediated activation of platelets. We have shown that Hb binding to glycoprotein (GP)-1b alpha on platelet, leads to platelet activation and binding to Von Willebrand factor (VWF) increases the VWF-platelet binding, promoting thrombus formation. Herein, we will briefly discuss the role of Hb in modulating the platelet functions in the backdrop of
pathophysiological conditions like hemolytic disorders including PNH and SCD.