Inherited thrombophilia is a genetic tendency to venous thromboembolism. The Factor V Leiden and prothrombin G20210A mutations are the most common defects, accounting for more than 50 percent of cases. Deficiencies in protein S, protein C, and antithrombin account for most of the remaining cases, while rare causes include the dysfibrinogenemias [1,2].
The total incidence of an inherited thrombophilia in subjects with a deep vein thrombosis ranges from 24 to 37 percent overall compared with about 10 percent in controls. (See "Overview of the causes of venous thrombosis", section on 'Inherited thrombophilia'.)
This topic review will discuss the genetics, prevalence, clinical presentation and diagnosis of the prothrombin G2010A mutation.
Issues related to screening for and management of the inherited thrombophilias are discussed separately. (See "Evaluation of the patient with established venous thrombosis" and "Screening for inherited thrombophilia in asymptomatic individuals" and "Management of inherited thrombophilia" and "Diagnosis and treatment of venous thrombosis and thromboembolism in infants and children".)
Prothrombin (factor II) is the precursor of thrombin, the end-product of the coagulation cascade. It is a vitamin K-dependent protein which is synthesized in the liver and circulates with a half-life of approximately three to five days. Vitamin K acts as a cofactor for posttranslational gamma-carboxylation of prothrombin which is required for functional activity. (See "Vitamin K and the synthesis and function of gamma carboxyglutamic acid".)