Inherited Hypercoagulable States

Abstract

Hypercoagulable states are a group of conditions associated with increased predisposition to thromboembolic events. Most of the inherited abnormalities recognized to date are associated with venous thromboembolism (VTE) rather than arterial thrombosis. The well-recognized inherited hypercoagulable states are the deficiencies of antithrombin, protein C and protein S, and the resistance to APC (factor V Leiden). These entities represent aberrations in the natural anticoagulant systems that exist in plasma. Other causes of inherited thrombophilia include abnormalities in the proteins of the fibrinolytic system, dysfibrinogenemias, deficiency of heparin cofactor II, abnormal thrombomodulin, elevated levels of histidine-rich glycoprotein, and the recently described variation in the prothrombin gene. One entity that has become firmly established as a predisposing factor for recurrent VTE is hyperhomocysteinemia. About half of VTE episodes in patients with inherited thrombophilias occur in relation to events that are generally recognized as predisposing states, such as surgery, pregnancy (particularly puerperium) and immobilization. In this review, the risks of VTE associated with inherited risk factors are discussed, and guidelines for the diagnosis and management are presented.