Association of idiopathic venous thromboembolism with single point-mutation at Arg506 of factor V

The Risk of Recurrent Venous Thromboembolism in Patients with an Arg506→Gln Mutation in the Gene for Factor V (Factor V Leiden)

“…5,6 This abnormality is caused by the substitution of a single amino acid -glutamine for arginine -at position 506 (Arg 506 → Gln, also referred to as factor V Leiden), in the coagulation factor V molecule. [7][8][9] In its activated form protein C is a natural anticoagulant that cleaves two activated coagulant factors, factor VIIIa and factor Va, thereby inhibiting the conversion of factor X to factor Xa and of prothrombin to thrombin. The mutation in the factor V molecule renders factor Va resistant to proteolysis by activated protein C. Venous thromboembolism develops in up to 40 percent of patients with resistance to activated protein C. [10][11][12] Although it is important to know the risk of recurrent venous thromboembolic disease in order to make decisions about therapy in carriers of the factor V Leiden mutation, the few studies of the risk have yielded conflicting results.…”

Acquired APC resistance and oral contraceptives: differences between two functional tests

“…The defect, called APC resistance, is often caused by a mutation Greengard et al, 1994;Voorberg et al, 1994; in factor V (factor V Leiden ) at a predominant APC cleavage site (Arg 506 → Gln). APC resistance associated with factor V Leiden is a hereditary defect that increases the risk for venous thrombosis some 7-fold in the case of heterozygosity (Koster et al, 1993;Rosendaal et al, 1995) and 80-fold in the case of homozygosity (Rosendaal et al, 1995).…”

“…This defect, called APC resistance, appears to be a common hereditary risk factor for venous thrombosis (Griffin et al, 1993;Koster et al, 1993;Rosendaal et al, 1995;, which in the majority of the cases is associated with a single point mutation in factor V Greengard et al, 1994;Voorberg et al, 1994;. This mutation, often referred to as factor V Leiden , causes the replacement of an amino acid (Arg506 → Gln) at a predominant APC cleavage site which renders the activated form of factor V, factor Va, less susceptible to proteolysis by APC (Aparicio & Dahlbäck, 1996;Heeb et al, 1995;Kalafatis et al, 1995;Nicolaes et al, 1995).…”

Factor VLeiden

“…Some studies attribute more than 95% of cases of APC resistance to the FV Leiden mutation [3,9,12]. FV Leiden is present in heterozygous form in 5% of the general Caucasian population and is less common or rare in other ethnic groups [13][14][15][16][17][18].…”