Factor V Leiden and factor VIII function as cofactors in the blood coagulation cascade to accelerate the rate of activation of factor X and prothrombin, respectively.

The classification of the factor VIII deficiency, generally based on the measurement of plasma activity levels of factor VIII, comprises severe (<1% normal factor VIII activity), moderate (1-4% factor VIII activity), or mild (5-25% factor VIII activity). Patients with hemophilia A and B and factor levels less than 1% of normal bleed frequently, with pronounced tendency of spontaneous bleeding episodes (e.g., in the absence of an obvious precipitating event). However, there are patients with equally low levels of factor VIII or factor IX who only bleed once or twice per year, or not at all. Also, there are some patients with unusually mild clinical presentation whose first symptomatic bleeding episode occurs relatively late in life The clinical phenotype is not always the same, even among related patients sharing the same molecular defect.

The simultaneous presence of a defect resulting in impeded blood clotting, and a hereditary defect predisposing to hypercoagulability, might play a role in ameliorating the hemorrhagic tendency in severe hemophiliacs [1-5]. Recent case reports point out that hemophiliacs carrying prothrombotic risk factors, as well as their primary blood clotting defect, are predisposed to venous thrombosis and cerebral complications [6,7]. Factor V Leiden (G1691A) and prothrombin G20210A variants are among the most common causes of inherited thrombophilia [8,9]. One of these two genotypes is now found in more than 60% of patients with a clinical history of familial thrombophilia. The genetic defect of coagulation factor V, known as factor V Leiden, produces a resistance to degradation by activated protein C (APC) and increases the risk of venous thromboembolism.

The aim of the present study is to investigate the inci­dence of factor V Leiden among the Bulgarian hemophilic population and to clarify phenotype-genotype correlations.