Genetic Testing for New DVT
Routine genetic thrombophilia testing is NOT recommended for adults with a first unprovoked DVT, as it does not change management or improve clinical outcomes compared to standard anticoagulation therapy. 1
Key Recommendation
The EGAPP Working Group (Evaluation of Genomic Applications in Practice and Prevention) found insufficient evidence that testing for Factor V Leiden or Prothrombin G20210A mutations leads to improved health outcomes in adults with idiopathic VTE. 1 Anticoagulation therapy provides comparable benefits regardless of mutation status, making routine genetic testing clinically unhelpful for treatment decisions. 1, 2
When Genetic Testing MAY Be Considered
Despite the general recommendation against routine testing, certain clinical scenarios warrant consideration of thrombophilia evaluation: 1
- Age <50 years with any venous thrombosis 3
- Unusual thrombosis sites (cerebral, mesenteric, portal veins) 1
- Recurrent thrombosis 1
- Thrombosis during pregnancy 1
- Strong family history of VTE in first-degree relatives 1
Specific Tests to Consider (If Testing Is Pursued)
Genetic/Molecular Tests:
- Factor V Leiden (R506Q) - most common hereditary thrombophilia, present in 15-20% of VTE patients 1
- Prothrombin G20210A mutation - second most common, present in 6% of VTE patients 1, 3
- Plasma homocysteine level (not MTHFR mutation testing) - levels >15 μmol/L confer increased VTE risk 1, 4
Functional Coagulation Assays:
Acquired Thrombophilias:
Important Caveats
Do NOT test for heterozygous MTHFR C677T mutation - this polymorphism is present in 30-40% of the general population and is NOT associated with venous thrombosis. 4 If homocysteine testing is performed and elevated (>15 μmol/L), this represents the actual risk factor, not the MTHFR genotype. 4
Timing matters for functional assays: Protein C, Protein S, and antithrombin levels can be affected by acute thrombosis and anticoagulation therapy, potentially yielding false results if tested during the acute event or while on warfarin. 1
Combined mutations increase risk substantially: Compound heterozygosity (Factor V Leiden + Prothrombin G20210A) carries a 20-fold increased risk for initial VTE, compared to 4-7 fold for Factor V Leiden alone and 2-4 fold for Prothrombin G20210A alone. 1, 3, 5
Why Testing Usually Doesn't Change Management
For patients with unprovoked DVT: Standard treatment is anticoagulation for at least 3 months, followed by risk-benefit assessment for extended therapy. 1 This approach is identical whether or not genetic mutations are present, as studies show comparable recurrence reduction with anticoagulation regardless of mutation status. 1, 2
Bleeding risk outweighs benefit in asymptomatic carriers: The annual risk of major bleeding on anticoagulation is approximately 3% with a 0.6% case fatality rate, which exceeds the absolute VTE risk in asymptomatic mutation carriers. 6 Therefore, prophylactic anticoagulation based solely on genetic testing is not recommended. 1, 6
Family member testing is not supported: Even when mutations are identified in index cases, testing asymptomatic family members does not improve outcomes, as the absolute risk of VTE remains low and prophylactic anticoagulation carries significant bleeding risk. 1, 6
Clinical Utility of Specific Mutations
Factor V Leiden: Heterozygosity increases recurrent VTE risk (OR 1.56), and homozygosity further increases risk (OR 2.65). 2 However, anticoagulation benefits are similar to non-carriers. 2
Prothrombin G20210A: Heterozygosity does NOT significantly predict recurrent VTE (OR 1.45,95% CI 0.96-2.2). 2, 7 Prospective studies confirm no increased recurrence risk in heterozygous carriers. 6
Double heterozygotes (Factor V Leiden + Prothrombin G20210A): Annual recurrence rate of 12.1% compared to 2.8-3.1% for single mutations, making this the only genetic scenario where extended anticoagulation may be more strongly justified. 7, 5