Laboratory Evaluation for Patients with Family History of Blood Clots
For asymptomatic patients with only a family history of VTE, routine thrombophilia testing is NOT recommended—the absolute risk remains low and testing does not change management in most cases. 1
However, targeted testing should be considered in specific high-risk scenarios where results would influence clinical decisions.
When to Consider Testing in Asymptomatic Family Members
Test selectively when knowledge of carrier status would directly influence management decisions:
First-degree relatives of individuals who developed VTE before age 50 should be considered for testing, as carrier annual VTE incidence is 0.45-0.67% versus 0.10% in non-carriers 2, 3
Women with family history contemplating oral contraceptives or pregnancy, where carrier status would influence contraceptive choice or peripartum thromboprophylaxis decisions 1, 2
Relatives of known Factor V Leiden carriers, particularly when results would guide decisions about hormonal therapy or pregnancy management 1, 3
Recommended Testing Panel
When testing is indicated, order the following comprehensive thrombophilia panel:
First-Line Genetic Testing (DNA-based):
- Factor V Leiden (G1691A) mutation - most common inherited thrombophilia 1, 3
- Prothrombin G20210A mutation - second most common, present in 1-2% of population 1, 3
Functional Coagulation Assays:
- Antithrombin III level/activity 1, 3, 4
- Protein C level/activity 1, 3, 4
- Protein S level/activity (free and total) 1, 3, 4
Additional Testing:
- Plasma homocysteine level - particularly if Factor V Leiden positive 1, 3
- Lupus anticoagulant panel 1
- Anticardiolipin antibodies 1
- Anti-β2-glycoprotein-1 antibodies 1
Testing Methodology Considerations
Use direct DNA-based genotyping when testing relatives of known carriers rather than functional assays, as this provides definitive results and distinguishes heterozygotes from homozygotes 2, 3
For functional assays (Protein C, Protein S, Antithrombin):
- Perform testing at least 2 weeks after discontinuing oral anticoagulation 4
- Wait at least 3 months after any acute thrombotic event 4
- DNA testing for Factor V Leiden and Prothrombin mutation is NOT affected by anticoagulation status 3
Important Clinical Caveats
The clinical utility of testing asymptomatic family members is limited because:
- Absolute VTE risk remains low even in carriers 1
- Longer-term prophylaxis yields comparable benefits regardless of mutation status 1
- Risk of anticoagulant-induced hemorrhage may outweigh benefits of primary prophylaxis 1
Family history alone is not a precise predictor of inherited thrombophilia:
- Even with strongly positive family history (≥2 first-degree relatives), only 46% have detectable inherited thrombophilia 5
- A negative family history does NOT exclude inherited thrombophilia due to low penetrance and possible de novo mutations 6
When Testing is NOT Recommended
Do NOT perform routine screening in:
- General asymptomatic population 1, 3
- Asymptomatic women before prescribing oral contraceptives (unless personal history of VTE or strong family history) 1, 3
- Asymptomatic individuals with environmental risk factors (surgery, trauma, malignancy) who should receive standard prophylaxis regardless 1, 3
Clinical Management Based on Results
If testing reveals thrombophilia in asymptomatic family members:
- Provide thromboprophylaxis during high-risk periods (surgery, prolonged immobilization, postpartum) rather than continuous anticoagulation 2, 3, 7
- For female carriers, knowledge influences peripartum thromboprophylaxis and contraceptive counseling 2, 7
- Counsel about modifiable risk factors (oral contraceptives, smoking, prolonged immobilization) 7
Patients should be informed before testing that: