When to Test for Factor V Leiden with Family History
Test relatives of individuals with known Factor V Leiden using direct DNA testing, particularly when knowledge may influence pregnancy management or oral contraceptive decisions. 1
Primary Testing Indications for Family Members
Relatives of individuals with venous thrombosis under age 50 should undergo testing, as the annual VTE incidence in carriers is 0.45-0.67% versus 0.10% in non-carriers. 1, 2 This represents a clinically meaningful risk difference that justifies screening in this specific population.
Relatives of individuals with documented Factor V Leiden should be considered for testing when knowledge of carrier status would influence clinical decisions, specifically: 1
- Women contemplating or using oral contraceptives
- Women planning pregnancy or currently pregnant
- Individuals facing high-risk situations requiring thromboprophylaxis decisions
Critical Context: Family History Alone Is Insufficient
A common pitfall is relying solely on family history of thrombosis to guide testing decisions. Family history in a first-degree relative has a positive predictive value of only 12-14% for detecting Factor V Leiden, making it an unreliable screening criterion by itself. 3 This means that most individuals with a positive family history will not have the mutation, and conversely, many carriers exist in families without obvious thrombotic histories.
When NOT to Test Family Members
Random screening of asymptomatic family members without specific risk factors or clinical decision points is not recommended. 1, 2 The key distinction is whether test results would change management:
- Do not screen relatives who have no upcoming decisions about oral contraceptives, pregnancy, or other high-risk situations 1
- Do not screen for general population surveillance purposes 2
- Do not screen relatives with active malignancy, as thromboprophylaxis would be indicated regardless of carrier status 1
Testing Methodology for Family Members
Use direct DNA-based genotyping when testing relatives of known Factor V Leiden carriers, rather than functional assays. 1 This approach provides definitive results and distinguishes heterozygotes from homozygotes, which has significant implications for management intensity.
Concurrent Testing Considerations
When testing family members for Factor V Leiden, simultaneously test for prothrombin G20210A mutation, as this is readily available, can be multiplexed with Factor V Leiden testing, and the combination creates synergistic thrombotic risk exceeding either mutation alone. 2 Research demonstrates that even after adjusting for prothrombin mutations, higher thrombotic rates persist in these families, suggesting additional unknown prothrombotic factors. 4
Clinical Utility of Family Testing
The value of identifying carriers among relatives lies in targeted prevention rather than treatment. Knowledge of carrier status guides thromboprophylaxis during high-risk periods (surgery, prolonged immobilization, postpartum period) rather than necessitating continuous anticoagulation. 2, 5 For female carriers, this information is particularly valuable for pregnancy planning, as Factor V Leiden influences peripartum thromboprophylaxis decisions. 5
By age 50, the probability of remaining free from VTE is reduced to 75% for carriers versus 93% for non-carriers in thrombophilic families, providing quantifiable risk information for counseling. 4
Special Populations Requiring Testing
Women with family history of thromboembolism, APC resistance, or documented Factor V Leiden mutation should be counseled and considered for testing when contemplating oral contraceptive use, as the cumulative thrombotic risk of Factor V Leiden and oral contraceptives is substantial. 1 However, routine screening before oral contraceptive prescription in the general population remains not recommended. 1, 2