Is it medically appropriate to test a 19-year-old male with Factor V Leiden deficiency for the prothrombin gene mutation, given his family history of the mutation?

Testing for Prothrombin Gene Mutation in a 19-Year-Old with Factor V Leiden

Yes, it is medically appropriate to test this 19-year-old male for the prothrombin gene mutation, as the American College of Medical Genetics explicitly recommends testing for prothrombin G20210A in all patients who test positive for Factor V Leiden. 1

Primary Recommendation

The American College of Medical Genetics provides clear guidance that patients testing positive for Factor V Leiden should be considered for molecular genetic testing for the prothrombin 20210A variant, as it is the most common other thrombophilia with overlapping phenotype for which testing is readily available. 1 The rationale is straightforward:

• The prothrombin mutation is present in 1-2% of the general population 1
• Its involvement in venous thromboembolism is well-established 1
• The DNA test is as simple as that for Factor V Leiden and can even be multiplexed with it 1

Why This Testing Matters for Risk Stratification

The presence of both mutations dramatically alters clinical management and thrombosis risk:

• Patients heterozygous for both Factor V Leiden and prothrombin 20210A mutation have high recurrence risk and should be considered for indefinite anticoagulation after any thrombotic event 2
• Factor V Leiden heterozygosity alone increases recurrent VTE risk (OR 1.56,95% CI 1.14-2.12), while homozygosity further increases risk (OR 2.65,95% CI 1.2-6.0) 3
• The combination of multiple thrombophilias creates synergistic risk that exceeds either mutation alone 1

Clinical Implications of Knowing Both Mutation Statuses

For Immediate Management:

• If he has both mutations, he would be considered for lifetime anticoagulation after any thrombotic event, similar to Factor V Leiden homozygotes 2
• Standard duration anticoagulation (3-6 months) is typically sufficient for Factor V Leiden heterozygotes alone with a single VTE episode 4

For Future Risk Situations:

• Knowledge guides thromboprophylaxis decisions during high-risk periods including surgery, trauma, prolonged immobilization, or if he develops other risk factors 2, 4
• The information is critical for counseling about modifiable risk factors such as smoking, prolonged immobilization, and future medical decisions 4

Family History Consideration

The fact that his biological father has the prothrombin gene mutation is relevant but does not change the recommendation to test, as the American College of Medical Genetics recommends prothrombin testing based on the Factor V Leiden diagnosis itself, not family history. 1 However, it does mean:

• He has a 50% chance of inheriting the prothrombin mutation from his father (assuming his father is heterozygous)
• If positive, first-degree relatives should be offered selective screening as the annual VTE incidence is 0.45-0.67% in carriers versus 0.10% in non-carriers 4

Comprehensive Testing Approach

The American College of Medical Genetics recommends that physicians ordering Factor V Leiden testing should also consider the utility of screening for other heritable thrombophilic factors, especially prothrombin 20210A and plasma homocysteine levels. 1 This means:

• Test for prothrombin G20210A mutation now 1
• Consider measuring plasma homocysteine levels as another potential risk factor 1, 2
• Functional coagulation assays for Protein S, Protein C, and antithrombin III deficiencies may be considered, especially given the strong family history of thrombophilia 1

Important Caveats

• This patient should be informed that thrombophilia testing is genetic, has implications for family members, and may have confidentiality and insurance implications 2
• Testing should ideally be performed when not on anticoagulation to avoid interference with functional assays, though DNA testing for prothrombin mutation is not affected by anticoagulation status 1
• The presence of these mutations does not mandate prophylactic anticoagulation in the absence of thrombosis, but knowledge guides decisions during high-risk clinical situations 2, 4