What is the recommended approach for a thrombophilia profile?

Thrombophilia Profile: Recommended Approach

Thrombophilia testing should be performed selectively and only in circumstances where the results will influence clinical decisions that impact patient outcomes, specifically targeting patients with high-risk presentations of venous thromboembolism. 1

When to Order Thrombophilia Testing

Thrombophilia testing is recommended in the following specific clinical scenarios:

• Age <50 years with any venous thrombosis
• Venous thrombosis in unusual sites (hepatic, mesenteric, cerebral veins)
• Recurrent venous thrombosis
• Venous thrombosis with strong family history of thrombotic disease
• Venous thrombosis in pregnant women or women taking oral contraceptives
• Relatives of individuals with venous thrombosis under age 50
• Myocardial infarction in female smokers under age 50 1

Testing may also be considered in:

• Venous thrombosis in patients >50 years (except when active malignancy is present)
• First-degree relatives of known Factor V Leiden carriers (to guide contraceptive and pregnancy management)
• Women with recurrent pregnancy loss, unexplained severe preeclampsia, placental abruption, intrauterine growth restriction, or stillbirth 1

Components of a Thrombophilia Profile

A comprehensive thrombophilia profile should include:

1. Factor V Leiden testing:

   • Direct DNA-based genotyping is recommended as the primary method
   • Alternatively, a Factor V Leiden-specific functional assay can be used initially, with positive results confirmed by DNA testing to distinguish heterozygotes from homozygotes 1, 2

2. Other common thrombophilias:

   • Prothrombin gene mutation (G20210A)
   • Hyperhomocysteinemia
   • Antiphospholipid antibodies 3

3. Less common but clinically significant deficiencies:

   • Antithrombin III deficiency
   • Protein C deficiency
   • Protein S deficiency 4, 5

Timing of Testing

• Do not perform testing during acute thrombosis
• Do not test during the initial 3-month period of anticoagulation
• For patients on heparin therapy or with known lupus anticoagulant, proceed directly to molecular testing rather than functional assays 1, 6

Interpretation and Clinical Application

• Factor V Leiden mutation produces a relative risk of venous thrombosis of approximately 7-fold in heterozygous state and 80-fold in homozygous state 2
• The presence of multiple thrombophilic defects significantly increases thrombotic risk
• Testing results should guide:
  • Duration of anticoagulation after a thrombotic event
  • Prophylactic strategies during high-risk periods (surgery, pregnancy, immobilization)
  • Family counseling regarding risk factors 6, 5

Important Caveats

• Random screening of the general population is not recommended 1
• Routine testing is not recommended for patients with arterial thrombotic disorders (except for myocardial infarction in young female smokers) 1
• Functional assays for APC resistance can be affected by pregnancy, oral contraceptives, lupus anticoagulant, and anticoagulant medications 2
• Testing should be targeted and selective to avoid potential harms of unnecessary testing, including psychological impact, inappropriate anticoagulation, and healthcare costs 6

Special Populations

For relatives of individuals with known thrombophilia:

• DNA-based testing is recommended over functional assays
• Results can guide decisions about oral contraceptive use and thromboprophylaxis during pregnancy 1

For pregnant women or those considering pregnancy:

• Testing should be considered in those with personal or family history of VTE
• Results can guide thromboprophylaxis decisions during pregnancy and postpartum 1, 6