What is the risk of arterial and venous thrombosis in individuals with a G20210A (Prothrombin G20210A) heterozygous mutation?

Risk of Arterial and Venous Thrombosis in G20210A Heterozygous Mutation

Heterozygosity for the prothrombin G20210A mutation increases the risk of venous thromboembolism (VTE) by 2-4 fold over the general population, while evidence for increased arterial thrombosis risk is less consistent and primarily limited to younger patients. 1

Venous Thrombosis Risk

• The prothrombin G20210A mutation is the second most common heritable risk factor for VTE, present in approximately 6% of individuals with an initial episode of venous thrombosis 1
• Heterozygosity for the G20210A mutation occurs in approximately 2.2% of non-Hispanic whites, 2.2% of Hispanic whites, and 0.6% of African Americans in the United States 1
• Population studies indicate that heterozygosity for the G20210A mutation increases the risk of an initial VTE episode by 2-4 fold compared to the general population 1
• For recurrent VTE, the evidence suggests that heterozygous carriers of the G20210A mutation have a risk similar to that of patients with normal genotype (hazard ratio 1.3; 95% CI, 0.7-2.3) 2

Arterial Thrombosis Risk

• The association between G20210A heterozygosity and arterial thrombotic events remains controversial 1
• Meta-analyses have found modest associations between the G20210A mutation and arterial thrombotic events (OR, 1.32; 95% CI, 1.03 to 1.69), with stronger associations in younger patients (<55 years of age) 1
• In a study of patients with angiographically documented coronary artery disease, no statistically significant difference was found in the prevalence of the G20210A mutation compared to controls (5.3% vs 3.1%, p=0.21) 3
• While the mutation itself may not be significantly associated with arterial disease, high prothrombin activity (which is influenced by the mutation) has been independently associated with coronary artery disease 3

Combined Risk Factors

• The risk of thrombosis increases significantly when G20210A heterozygosity is combined with other thrombotic risk factors 4:
  • Oral contraceptive use in women with G20210A heterozygosity significantly increases VTE risk 4
  • Compound heterozygosity (G20210A plus Factor V Leiden) is associated with a 20-fold increased risk for initial VTE episodes 1
  • Patients heterozygous for both G20210A and Factor V Leiden have high recurrence risk and should be considered for indefinite anticoagulation therapy 5

Clinical Implications

• Testing for the G20210A mutation is recommended for patients under age 50 with any venous thrombosis, patients with venous thrombosis in unusual sites, and those with recurrent venous thrombosis 6
• For patients with a first VTE and heterozygous G20210A mutation without other risk factors, anticoagulation for 3 months is generally recommended for provoked events, while unprovoked events require at least 3 months with consideration for extended therapy 5
• Patients with G20210A heterozygosity alone (without other thrombophilic conditions or recurrent events) do not routinely require long-term anticoagulation 5
• Knowledge of G20210A status in asymptomatic relatives can guide antithrombotic prophylaxis during high-risk periods, such as surgery or postpartum periods 5, 6

Common Pitfalls and Caveats

• Do not assume that all G20210A carriers have the same risk profile; risk varies significantly based on the presence of additional thrombophilic conditions and other risk factors 5, 4
• Women with G20210A heterozygosity should avoid combined oral contraceptives due to the significantly increased thrombotic risk 5, 4
• The risk of major bleeding with chronic anticoagulant therapy must be carefully weighed against the thrombotic risk before committing to lifelong anticoagulation 5
• Regular reassessment of the risk/benefit ratio is essential for patients on long-term anticoagulation 5