Activation state of platelets in experimental severe hemophilia A

Factor VIII (FVIII) is a key protein of the coagulation cascade where it acts as the cofactor of activated factor IX. Upon activation, FVIII dissociates from von Willebrand factor and binds to phospholipids at the surface of activated platelets to form the tenase complex, thus leading to the activation of factor X, to a burst of generation of thrombin and to the formation of fibrin that consolidates the platelet clot. 1 Abnormalities in the gene encoding FVIII lead to hemophilia A (HA), a rare Xlinked recessive hemorrhagic disorder that concerns one male in 5000. Depending on the residual activity of FVIII in plasma, HA is classified as severe (<1%), moderate (1-5%) or mild (5-25%). 2 Although this classification correlates with the bleeding phenotype, about 10% of severe HA patients rarely bleed spontaneously, indicating that FVIII activity is not the only parameter defining the phenotypic severity of the disease. n their recent publication, 4 van Bladel et al. investigated the basal state of activation and responsiveness of circulating platelets under conditions of abnormal hemostasis as a potential parameter influencing the bleeding phenotype of the patients. They found that the state of activation of platelets is up-regulated in patients with severe HA. The percentage of platelets expressing CD62P (Pselectin) at their surface was greater in patients with severe HA (15.9%) as compared to that in patients with mild/moderate HA (8.2%) and in healthy controls (6.4%). An earlier report had, however, failed to find signs of enhanced platelet pre-activation in patients with severe HA.