Prothrombin Gene Mutation

A common polymorphism in the prothrombin (factor II) gene, has been associated with an increased risk of venous thromboembolism. The prothrombin mutation, known as G20210A, involves a guanine to adenine substitution at position 20210 in the untranslated region gene. Patients with this mutation have increased plasma prothrombin levels, possibly due to increased translation efficiency or greater stability of mRNA.

Four independent studies have demonstrated that this prothrombin mutation is associated with a two to fivefold increase in risk for venous thromboembolism. It may exist in either a heterozygous or homozygous state. Heterozygotes have a 3-fold increased risk of venous thrombosis. The mutation is found in 1 to 3% of the general Caucasian population, in 5 to 10% of patients with thrombosis and in up to 20% of patients with familial thrombosis. The mutation is very rare in non-Caucasian populations (<0.6% in African Americans and 0% in Asians). As with other prothrombotic risk factors, the prothrombin mutation interacts synergistically with other hereditary risk factors for venous thromboembolism, such as the factor V Leiden mutation.

Controversy exists regarding a possible association between the prothrombin mutation and arterial thrombosis. One study indicated that the polymorphism might increase the risk of myocardial infarction in young women, especially smokers. Another study showed evidence of a relationship with cerebrovascular ischemic disease in young patients.

The clinical utility of genetic testing depends on the ability of testing results to change patient management in a way that improves clinical outcomes. The clinical utility of genetic tests for thrombophilia is based on the overall risk of thromboembolism and the risk to benefit ratio of anticoagulant therapy. Two medical societies have issued position statements that question the value of genetic testing.

The American College of Chest Physicians (ACCP) published guidelines for the treatment of thromboembolic disease in 2008. They stated that the presence of hereditary thrombophilia has not been used as a major factor to guide duration of anticoagulation therapy for venous thromboembolism because it is not a major risk factor for recurrence.

In 2011, the Evaluation of Genomic Applications in Practice and prevention Working Groups (EGAPP) stated that:

  • There is no evidence that knowledge of Factor V Leiden mutation or prothrombin gene mutation status affects anticoagulation therapy to avoid recurrence
  • There is convincing evidence that treatment beyond three months reduces the recurrence of venous thromboembolism regardless of mutation status.
  • There is no evidence that knowledge of Factor V Leiden mutation or prothrombin gene mutation status among asymptomatic family members of patients with venous thromboembolism leads to prophylactic anticoagulation therapy.

Laboratory testing for the prothrombin gene mutation is most commonly ordered for patients with a history of unexplained, recurrent or familial thrombosis. Prothrombin gene mutation is detected by PCR analysis. Some laboratories may include it in a hypercoagulability or venous thromboembolism panel. Results are reported as Not Present, Present-Heterozygous, or Present-Homozygous.

Reference value is not present.

Specimen requirement is on 5 mL lavender top (EDTA) tube of blood.

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