Genetic risk factors for phlebothrombosis: New aspects under special consideration of the inherited resistance to activated protein C (coagulation factor V Leiden).

Beside the inherited deficiencies in antithrombin III, protein C and protei n S the resistance to activated protein C is the so far most common thrombo philic defect, A point mutation in the gene of factor V (guanine for adenin e substitution at position 1691) has been described as the underlying molec ular basis, This defect has been referred as to factor V Leiden mutation ac cording to the place where it has been found first, In the general European population a 2-7% prevalence of this defect has been reported, The heteroz ygous factor V Leiden mutation leads to a 5-10 fold, the homozygous form to a 50-100 fold increased risk of thrombosis, Patient DNA can be screened fo r this mutation by use of the polymerase chain reaction, The evaluation of patients with venous thromboembolism should in addition t o the determination of antithrombin III, protein C and protein S include th e search for resistance to activated protein C, The functional resistance t o activated protein C assay should be performed first line followed by a ge netic analysis if indicated. As long as appropriate evidence from clinical trials is not available the benefit of a prolonged anticoagulation in patie nts with recurrent venous thromboembolism or life threatening first episode s and the presence of factor of factor V Leiden mutation has to be weighed up individually against the potential harm by severe hemorrhage under this therapy.