When is thrombophilia testing recommended?

Thrombophilia Testing Recommendations

Thrombophilia testing is recommended for patients under age 50 with any venous thrombosis, those with thrombosis in unusual sites, recurrent thrombosis, strong family history of thrombotic disease, and pregnant women or women on oral contraceptives who develop venous thrombosis. 1

Key Indications for Thrombophilia Testing

• Testing should be performed in patients with venous thrombosis under age 50 2, 1
• Testing is indicated for venous thrombosis in unusual sites (hepatic, mesenteric, cerebral veins) 2, 1
• Recurrent venous thrombosis warrants thrombophilia testing 2, 1
• Patients with venous thrombosis and a strong family history of thrombotic disease should be tested 2, 1
• Testing is recommended for venous thrombosis in pregnant women or women taking oral contraceptives 2
• Myocardial infarction in female smokers under age 50 is an indication for testing 2
• Young patients (<50 years) who develop acute arterial thrombosis without other risk factors for atherosclerotic disease may benefit from testing 2

Additional Situations Where Testing May Be Considered

• Venous thrombosis in patients over age 50, except when active malignancy is present 2
• Relatives of individuals known to have factor V Leiden, particularly when knowledge may influence pregnancy management or oral contraceptive use decisions 2
• Women with recurrent pregnancy loss or unexplained severe preeclampsia, placental abruption, intrauterine growth restriction, or stillbirth 2, 1

Situations Where Testing Is NOT Recommended

• Random screening of the general population 2
• Routine testing for patients with personal or family history of arterial thrombotic disorders (except specific situations noted above) 2
• Routine screening for asymptomatic women contemplating or using oral contraceptives 2
• Testing during acute thrombosis or during the initial 3-month period of anticoagulation (may lead to inaccurate results) 3
• Screening of asymptomatic individuals with environmental risk factors such as surgery, trauma, paralysis, and malignancy 2

Testing Approach

• Either direct DNA-based genotyping or a factor V Leiden-specific functional assay is recommended initially 2, 1
• Patients who test positive by functional assay should undergo confirmatory DNA testing to distinguish heterozygotes from homozygotes 2, 1
• Patients on heparin therapy or with known lupus anticoagulant should proceed directly to molecular testing 2
• When testing relatives of individuals with known factor V Leiden, DNA testing is recommended 2

Comprehensive Testing Strategy

• When testing for factor V Leiden, consider concurrent testing for other common thrombophilias, particularly prothrombin 20210A mutation 2, 1
• Protein S, protein C, and antithrombin III deficiencies should be considered, especially with strong family history of venous thrombosis 2
• Hyperhomocysteinemia should be considered in patients positive for factor V Leiden 2, 1

Clinical Implications and Management Considerations

• Factor V Leiden homozygotes should be considered for lifetime antithrombotic prophylaxis after a thrombotic event 1
• Patients heterozygous for both factor V Leiden and prothrombin 20210A mutation have high recurrence risk and should be considered for indefinite anticoagulation 1
• Knowledge of thrombophilia status can guide prophylaxis decisions during high-risk periods, particularly postpartum 1
• The risk of major bleeding with chronic warfarin therapy may reach 8% per year, requiring careful risk-benefit assessment 1

Important Caveats

• Thrombophilia testing should not be performed during acute thrombosis or initial anticoagulation period (first 3 months) as results may be inaccurate 3
• Testing should be highly selective and performed only when results will influence patient management decisions 3
• Despite common practice, testing for inherited thrombophilia has not been shown to reduce recurrence of venous thrombosis 4
• Patients should be informed that thrombophilia testing is genetic, has implications for family members, and may have confidentiality and insurance implications 2