What laboratory tests are needed for a patient with recurrent superficial thrombosis?

Laboratory Testing for Recurrent Superficial Thrombosis

For patients with recurrent superficial thrombosis, a comprehensive thrombophilia workup should include testing for Factor V Leiden, prothrombin gene mutation, plasma homocysteine levels, and functional coagulation assays for antithrombin III, protein C, and protein S. 1

Initial Laboratory Evaluation

The following tests should be performed for patients with recurrent superficial thrombosis:

First-line Tests:

• Complete blood count with platelet count
• Prothrombin time (PT)
• Activated partial thromboplastin time (aPTT)
• Factor V Leiden testing (either direct DNA-based genotyping or a Factor V Leiden-specific functional assay) 1
• Prothrombin 20210A variant testing 1
• Plasma homocysteine levels 1
• Functional coagulation assays for:
  • Antithrombin III
  • Protein C
  • Protein S 1

Additional Testing:

• Lupus anticoagulant
• Anticardiolipin antibodies 1
• Anti-β2-glycoprotein-1 antibodies
• Factor VIII levels

Testing Methodology

For Factor V Leiden:

• Either direct DNA-based genotyping or a Factor V Leiden-specific functional assay (activated protein C resistance) is recommended 1
• If using a functional assay, patients who test positive should undergo DNA testing for confirmation and to distinguish heterozygotes from homozygotes 1
• For patients on heparin therapy or with known lupus anticoagulant, direct molecular testing is preferred 1

For Activated Protein C Resistance (APC-R):

• Predilution assays are recommended due to their high sensitivity and specificity for Factor V mutations 1
• Sample handling requires double-centrifugation to ensure residual platelet count <10.0 × 10^9/L 1
• Testing should be performed within 4 hours of collection or plasma should be properly frozen 1

Special Considerations

• Hyperhomocysteinemia interacts synergistically with Factor V Leiden, increasing the relative risk of venous thrombosis 20-fold compared to individuals without either risk factor 1
• Patients with recurrent superficial thrombosis should be evaluated for both genetic and acquired risk factors, as multiple thrombophilic factors often coexist 1
• Testing for thrombophilia is particularly important in patients with:
  • Thrombosis at unusual sites
  • Strong family history of thrombotic disease
  • Recurrent venous thrombosis 1

Common Pitfalls and Caveats

1. Timing of testing: Avoid testing during acute thrombotic events or while on anticoagulation therapy, as this may affect results
2. Sample handling: Improper sample preparation can lead to false results, especially for functional assays
3. Interpretation challenges:
   • Factor deficiencies, pregnancy, oral contraceptive use, and lupus anticoagulant can affect APC-R assays 1
   • Plasma homocysteine measurement is more informative than molecular testing for MTHFR mutations 1
4. Comprehensive approach: Testing for a single thrombophilic factor is insufficient, as venous thrombosis is often multifactorial 1

Follow-up Testing

• If initial testing is negative but clinical suspicion remains high, consider referral to a hematologist for further specialized testing
• For patients with positive Factor V Leiden or APC resistance, molecular genetic testing for other common thrombophilias (particularly prothrombin 20210A variant) is recommended 1

By following this structured approach to laboratory testing, clinicians can effectively identify underlying thrombophilic conditions in patients with recurrent superficial thrombosis, allowing for appropriate management to reduce the risk of future thrombotic events.