The investigation and management of inherited thrombophilia

Abstract

Inherited thrombophilia can be defined as a genetically determined tendency to venous thromboembolism. Genetic risk factors for venous thrombosis include antithrombin deficiency, protein C deficiency, protein S deficiency, activated protein C resistance due to the factor V gene Leiden mutation, inherited hyperhomocysteinaemia, elevated factor VIII levels and the prothrombin gene G20210 A variant. A genetic risk factor is now identifiable in up to 50% of unselected patients with venous thrombosis. Individuals with inherited thrombophilia may develop venous thrombosis at a young age, or they may present with thrombosis at an unusual site or in the apparent absence of any precipitating event. A family history of thrombosis is suggestive of inherited thrombophilia. Laboratory investigations for inherited thrombophilia should include testing for activated protein C resistance and the factor V gene Leiden mutation, and screening for deficiencies of antithrombin, protein C or protein S. Screening for the prothrombin gene G20210 A variant, and measurement of plasma factor VIII and homocysteine levels should be considered in individual cases. In recent years the multifactorial nature of thrombophilia, both circumstantially and on a genetic level, has become increasingly apparent. Individuals with more than one inherited thrombophilia risk factor are particularly prone to thrombosis and their identification is a priority.