Role of platelet abnormalities in MPN-associated thrombophilia. Many studies have investigated the contribution of platelets in the onset of the thrombophilic state in MPNs, and it is now clear that the increased platelet count is not a major element in the risk of thrombosis. Rather, platelet qualitative abnormalities have been implicated in the pathogenesis of hypercoagulability in ET and PV patients. Increased expression of P-selectin, thrombospondin, and the activated fibrinogen receptor GPIIb/IIIa by platelets has been found to be correlated with thrombosis. The formation of platelet-leukocyte aggregates, platelet activation, and microparticle shedding are also implicated in the pathogenesis of thrombosis in these patients. Microparticles expose the anionic phosphatidylserine, providing a catalytic surface for the generation of thrombin, which further amplifies platelet activation.