What testing is recommended at primary care for individuals with a family history of blood clots?

Testing Recommendations for Individuals with Family History of Blood Clots in Primary Care

Routine thrombophilia testing is not recommended for all individuals with a family history of blood clots in the primary care setting, but targeted testing should be offered to specific high-risk groups.

Who Should Be Tested

Testing for thrombophilia should be considered in the following situations:

• Relatives of individuals with venous thrombosis under age 50 1, 2
• Individuals with a strong family history of thrombotic disease (especially first-degree relatives affected) 1, 2
• Women with family history of blood clots who are:
  • Considering oral contraceptive use 1
  • Pregnant or planning pregnancy 1, 2
  • Have history of pregnancy complications (recurrent loss, preeclampsia, placental abruption, growth restriction, stillbirth) 1, 2

Testing Panel Recommendations

When testing is indicated, the following comprehensive panel should be ordered:

• Genetic tests:

  • Factor V Leiden mutation (R506Q)
  • Prothrombin G20210A variant

• Functional coagulation assays:

  • Protein C deficiency
  • Protein S deficiency
  • Antithrombin III deficiency
  • Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-β2 glycoprotein I) 2

Important Testing Considerations

• Timing of testing: Testing should be performed either before anticoagulation is started or at least 2 weeks after discontinuation of anticoagulation, as therapy can affect functional test results 2

• Pre-test counseling: Patients should be informed about:

  • Potential implications for family members
  • Possible impact on insurance and employment
  • How results might affect clinical management 2

Clinical Significance and Risk Assessment

• Family history alone increases VTE risk approximately 2-fold, and up to 4-fold when multiple relatives are affected 3
• Family history remains a significant risk indicator regardless of identified genetic factors 3
• Risk increases substantially with combined risk factors:
  • Heterozygous Factor V Leiden: 3-7 fold increased risk
  • Homozygous Factor V Leiden: 18 times higher risk
  • Multiple thrombophilic factors: up to 20-fold increased risk 2

Pitfalls and Caveats

• Poor correlation: Family history corresponds poorly with known genetic risk factors, suggesting unidentified hereditary components 3
• Limited utility for recurrence prediction: Family history does not reliably predict recurrence risk in those who have already had a VTE event 4
• Potential harms: Consider psychosocial effects and insurance implications of positive results 1
• Cost-effectiveness: Random screening of general population is not recommended 1, 2

Special Considerations

• Testing for thrombophilia in asymptomatic family members requires careful risk-benefit analysis
• For women considering oral contraceptives with positive family history, alternative contraception methods may be considered if testing reveals thrombophilia
• The presence of environmental risk factors (surgery, trauma, malignancy) does not preclude testing when family history is significant 1

By following these evidence-based recommendations, primary care providers can appropriately identify individuals who would benefit from thrombophilia testing while avoiding unnecessary testing in low-risk populations.