Issues concerning the laboratory investigation of inherited thrombophilia

Inherited thrombophilia, defined as an increased familial tendency to develop thrombosis, may be due to congenital deficiencies or abnormalities of antithrombin, protein C or protein S; to the presence of a point mutation in the factor V gene (G1691A, factor V Leiden) leading to a poor anticoagulant response to activated protein C; or to the presence of a mutation in the prothrombin gene (G20210A) leading to increased plasma levels of prothrombin. The laboratory investigation of inherited thrombophilia should be limited to patients with a history of venous thromboembolism and, if positive, to their family members even though they are still asymptomatic. There is no indication for indiscriminate screening of the general population or screening of asymptomatic women before prescribing oral contraceptives. Testing should be based on the phenotype for antithrombin, protein C and protein S; on the phenotype and genotype (factor V Leiden mutation) for activated protein C resistance; and on the genotype (G20210A mutation) for hyperprothrombinemia. Phenotypic testing should be performed no sooner than three months after acute thrombotic events and at least 2 weeks after discontinuation of oral anticoagulant treatment.