Factors that influence the bleeding phenotype in severe hemophilic patients.

Hemophilia A and B are rare, X-linked bleeding disorders resulting from a partial or total deficiency of functionally active coagulation factor VIII or factor IX, respectively. Endogenous factor levels have traditionally been used to characterize the severity of the disorder, with severe hemophilia considered as circulating levels of factor less than 1% of normal. Identifying patients with severe hemophilia is essential to effective treatment, since these patients are at highest risk of spontaneous life or limb-threatening bleeding and disability resulting from repeated joint bleeding and are most likely to benefit from prophylaxis. However, there is variability in bleeding tendency, even among patients with severe hemophilia. This article will review potential modifiers of hemophilia-associated bleeding other than endogenous factor activity, which may influence bleeding tendencies and complications in hemophilic patients considered to have severe hemophilia. These potential modifiers include physiologic factors, such as elements of the hemostatic system; pathophysiologic factors, such as hemophilic arthropathy, associated inflammation, and angiogenesis; and others, such as seasonal variation, body weight, and physical activity.