What is the significance and treatment for a prothrombin gene mutation 20210A?

From the Guidelines

Prothrombin gene mutation 20210A is a significant genetic risk factor for developing abnormal blood clots, and treatment depends on whether you've already had a clot or just carry the mutation. For patients who have experienced a blood clot with this mutation, anticoagulation therapy is typically recommended, usually with direct oral anticoagulants (DOACs) like apixaban (Eliquis) 5mg twice daily or rivaroxaban (Xarelto) 20mg daily with food. Alternatively, warfarin (Coumadin) with a target INR of 2-3 may be used. The duration of treatment varies based on whether the clot was provoked by a temporary risk factor (3-6 months) or unprovoked (often indefinite) 1.

Key Considerations

• For those who only carry the mutation without having had a clot, preventive anticoagulation is not routinely recommended, but temporary prophylaxis may be advised during high-risk situations like surgery, pregnancy, or long flights.
• In these cases, low molecular weight heparin like enoxaparin (Lovenox) 40mg subcutaneously daily may be prescribed, as suggested by the American College of Chest Physicians evidence-based clinical practice guidelines 1.
• This mutation increases blood clotting risk by causing elevated levels of prothrombin (Factor II), making blood more likely to clot.
• The risk is further increased when combined with other factors like oral contraceptive use, pregnancy, or additional clotting disorders, so lifestyle modifications including maintaining healthy weight, staying active, and avoiding smoking are important preventive measures.

Pregnancy Considerations

• For pregnant women with no prior history of VTE who are known to be homozygous for factor V Leiden or the prothrombin 20210A mutation and have a positive family history for VTE, antepartum prophylaxis with prophylactic- or intermediate-dose LMWH and postpartum prophylaxis for 6 weeks with prophylactic- or intermediate-dose LMWH or vitamin K antagonists targeted at INR 2.0 to 3.0 is recommended 1.
• For pregnant women with no prior history of VTE who are known to be homozygous for factor V Leiden or the prothrombin 20210A mutation and who do not have a positive family history for VTE, antepartum clinical vigilance and postpartum prophylaxis for 6 weeks with prophylactic- or intermediate-dose LMWH or vitamin K antagonists targeted at INR 2.0 to 3.0 is suggested 1.

From the FDA Drug Label

For patients with a first episode of DVT or PE who have documented deficiency of antithrombin, deficiency of Protein C or Protein S, or the Factor V Leiden or prothrombin 20210 gene mutation, homocystinemia, or high Factor VIII levels (>90th percentile of normal), treatment for 6 to 12 months is recommended and indefinite therapy is suggested for idiopathic thrombosis The prothrombin 20210A gene mutation is a thrombophilic condition that increases the risk of venous thromboembolism (VTE). The treatment for patients with this mutation who have had a deep vein thrombosis (DVT) or pulmonary embolism (PE) is anticoagulation therapy with warfarin for 6 to 12 months, with indefinite therapy suggested for idiopathic thrombosis. The target INR for warfarin therapy is 2.5 (range, 2.0 to 3.0) 2.

• Key points:
  • Prothrombin 20210A gene mutation is a thrombophilic condition
  • Treatment: anticoagulation therapy with warfarin for 6 to 12 months
  • Target INR: 2.5 (range, 2.0 to 3.0)
  • Indefinite therapy may be suggested for idiopathic thrombosis

From the Research

Significance of Prothrombin Gene Mutation 20210A

• The prothrombin gene mutation 20210A is associated with an increased risk of venous thromboembolism (VTE) 3, 4, 5.
• The mutation is a risk factor for a first venous thromboembolic episode, but the long-term risk for recurrent VTE is similar to that of patients with a normal genotype 3.
• The risk of thrombosis is increased when the prothrombin mutation is present together with other thrombotic risk factors, such as factor V Leiden or oral contraceptive use 4.

Treatment for Prothrombin Gene Mutation 20210A

• Carriers of the prothrombin mutation should be treated with oral anticoagulants after a first deep venous thrombosis for a similar length of time as patients with a normal genotype 3.
• The use of oral contraceptives by women with the prothrombin G20210A variant or factor V Leiden, either alone or combined with other thrombotic risk factors, is associated with a significant increase in the risk of venous thrombosis 4.
• Screening for thrombophilia in otherwise healthy children younger than 15 years who belong to families with inherited defects predisposing to thrombosis seems unjustified, as the thrombotic risk in these children appears to be very low 6.

Interaction with Other Risk Factors

• The prothrombin gene mutation does not seem to increase the risk of arterial thrombosis, such as myocardial infarction or stroke 5.
• The risk of venous thrombosis associated with the prothrombin mutation is smaller in magnitude than that associated with factor V Leiden 5.
• The presence of other thrombotic risk factors, such as antiphospholipid antibodies, can increase the risk of thrombosis in carriers of the prothrombin mutation 7.