Thrombophilic disorders

Thrombophilic disorders are defined as inherited or acquired defects, pathophysiologically and statistically associated with an increased risk of thrombosis. Venous thromboembolism (VTE) is the most prominent manifestation of thrombophilia. Inherited abnormalities include deficiencies of antithrombin, protein C, and protein S, factor V Leiden mutation, and the prothrombin G20210A mutation. Acquired APC resistance, hyperhomocysteinemia, sticky platelet syndrome and elevated levels of factors VIII, IX and XI also have been associated with an increased risk of VTE. Acquired thrombophilic disorders are represented by antiphospholipid syndrome and cancer. The association between thrombophilia and the risk of recurrent VTE is weaker than the association between thrombophilia and the risk of the first manifestation of VTE. Long-term anticoagulant therapy with warfarin is not recommended in primary prevention for the thrombophilia carriers, however, short-term prophylaxis with low-molecular-weight heparin in high risk conditions is indicated. The risk of VTE recurrence is slightly increased in patients with the factor V Leiden or the prothrombin gene mutation, moderately increased in those with mild hyperhomocysteinemia, and highest in those with elevated factor VIII levels or antiphospholipid syndrome. Idiopathic VTE, residual thrombosis, proximal thrombosis, or elevated D-dimer levels after cessation of anticoagulant therapy are additional important predictors of recurrent VTE.

Contrary to the VTE, most inherited thrombophilic defects do not appear to be important risk factors for arterial thrombosis.

For women with thrombophilic defects, the risk of pregnancy loss, intrauterine growth retardation, placental abruption, severe pre-eclampsia and the HELLP syndrome is increased about 2-fold. Obstetric complications, particularly recurrent spontaneous abortions or intra-uterine fetal death, may be the first manifestation of the antiphospholipid antibody syndrome. The pharmacological thromboprophylaxis during pregnancy is useful in patients with thrombophilic disorders and previous pregnancy complications.

Routine screening of patients with VTE for a thrombophilic defect is not justified, but some specific subcategories of patients may benefit from thrombophilia testing. The thrombophilic disorders are worth testing only if appropriate mechanisms for subsequent clinical counseling exist.

Keywords: Key words: thrombophilia, venous thromboembolism, pregnancy, screening, thromboprophylaxis.