When is testing for thrombophilias (blood clotting disorders) recommended?

Thrombophilia Testing Recommendations

Thrombophilia testing should only be performed in highly selective circumstances where the information will influence patient management decisions, and should not be done routinely for all patients with venous thromboembolism (VTE). 1, 2

Recommended Indications for Testing

Thrombophilia testing is recommended in the following specific situations:

• Venous thrombosis in patients under age 50 3, 1
• Thrombosis in unusual sites (hepatic, mesenteric, cerebral veins) 3, 1
• Recurrent venous thrombosis 3, 1
• Venous thrombosis with a strong family history of thrombotic disease 3, 1
• Venous thrombosis in pregnant women or women taking oral contraceptives 3, 1
• Relatives of individuals with venous thrombosis under age 50 3, 1
• Myocardial infarction in female smokers under age 50 3, 1
• Women with recurrent pregnancy loss, unexplained severe preeclampsia, placental abruption, intrauterine growth restriction, or stillbirth 3, 1
• Patients with suspected antiphospholipid syndrome (especially with both venous and arterial thrombosis) 3, 4

Situations Where Testing May Be Considered

• Venous thrombosis in patients over age 50, except when active malignancy is present 3
• Relatives of individuals known to have factor V Leiden (may influence pregnancy management and oral contraceptive use decisions) 3, 1
• Young patients (<50 years) who develop arterial thrombosis without other risk factors for atherosclerotic disease 3

When Testing Should NOT Be Done

• Random screening of the general population 3, 1
• Routine testing for patients with arterial thrombotic disorders (except specific situations noted above) 3, 1
• Routine screening of asymptomatic women contemplating or using oral contraceptives (except those with personal history of thromboembolism) 3, 1
• During acute thrombosis or initial 3-month period of anticoagulation (may affect test results) 2
• Patients with provoked VTE with clear transient risk factors 2
• Asymptomatic individuals with environmental risk factors (surgery, trauma, etc.) 3
• Prenatal testing or routine newborn screening 3

Timing of Testing

Testing should not be performed during:

• Acute thrombosis
• The initial 3-month period of anticoagulation
• Active inflammation
• Pregnancy
• While on hormonal therapy

These conditions can affect test results, particularly for functional assays like protein C, protein S, and antithrombin levels 2.

Recommended Testing Panel

When testing is indicated, consider:

1. Factor V Leiden mutation (R506Q) - most common hereditary thrombophilia 3, 1
2. Prothrombin G20210A variant - second most common hereditary thrombophilia 3, 1
3. Functional assays for protein C, protein S, and antithrombin III deficiencies (especially with strong family history) 3, 1
4. Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, anti-β2 glycoprotein I) 3, 4
5. Plasma homocysteine levels (especially in those positive for Factor V Leiden) 3, 1

Clinical Impact and Limitations

• Despite identifying thrombophilia, testing has not been shown to reduce VTE recurrence rates 5
• Known thrombophilias do not affect the efficacy of anticoagulants or impact the choice or dose of anticoagulant 4
• Inherited thrombophilias have at most a slightly increased risk for recurrence after unprovoked VTE 6
• Testing may lead to overestimating thrombosis risk and underestimating bleeding risk in patients on anticoagulation 4

Important Caveats

• Patients should be counseled about the genetic implications of testing and potential impact on family members 1
• The European Society of Cardiology recommends testing for thrombophilia (including antiphospholipid antibodies) in patients with VTE without an identifiable risk factor, especially when considering long-term anticoagulation decisions 3
• Antiphospholipid syndrome appears to carry a higher risk of recurrence than inherited thrombophilias 4
• Heterozygous Factor V Leiden or prothrombin 20210A mutation alone generally do not warrant extended anticoagulation based on current evidence 3

In summary, thrombophilia testing should be reserved for specific clinical scenarios where results would influence management decisions, and should not be performed routinely after VTE events.