Platelets as Modifiers of Clinical Phenotype in Hemophilia

Platelets occupy a central role in the maintenance of hemostasis by adhering to sites of vascular injury and facilitating thrombin generation, which leads to the formation of a fibrin clot. Patients with hemophilia exhibit defective thrombin generation secondary to reduced plasma factor concentrations, which can lead to excessive and sometimes life-threatening bleeding. Individuals differ greatly with respect to platelet function and platelets from different individuals differ inherently in their ability to enact thrombin generation, the key coagulative process that is deficient in hemophilia. Similarly, some patients with hemophilia seem to bleed less often than others despite exhibiting similar plasma factor levels. The biologic factors that underlie this phenotypic variability remain poorly understood, but evidence is reviewed supporting a role for platelets and platelet-related factors in modifying bleeding tendency in patients with hemophilia and potential directions for further clinical research in this area are discussed.