Hypercoagulability Workup: Who Should Be Evaluated
Patients with specific risk factors, clinical presentations, and family history should undergo hypercoagulability workup to identify underlying thrombophilic conditions that may affect morbidity and mortality.
Patient Selection for Hypercoagulability Evaluation
High-Priority Candidates
- Patients with thrombosis at a young age (<45 years) 1, 2
- Patients with recurrent venous thromboembolism (VTE) 1, 2
- Thrombosis at unusual or atypical sites (cerebral, mesenteric, portal, or hepatic veins) 1
- Strong family history of thrombotic disorders 1, 2
- Warfarin-induced skin necrosis 1
- Patients with unexplained pregnancy loss or complications 3
Secondary Considerations
- Patients with unprovoked VTE (no clear precipitating factors) 3
- Patients with thrombosis despite adequate anticoagulation 3
- Patients with multiple risk factors (age >40 years, cancer, prior VTE) who develop thrombosis 4
- Patients with arterial thrombosis without traditional risk factors 5
Specific Clinical Scenarios Warranting Evaluation
Surgical and Perioperative Settings
- Patients with high surgical risk (major surgery) AND additional risk factors:
Pregnancy-Related
- Women with history of:
- Recurrent pregnancy loss
- Severe preeclampsia
- Intrauterine growth restriction
- Placental abruption 3
Cancer-Associated
- Patients with:
Recommended Testing Approach
First-Line Tests
- Complete blood count with peripheral blood smear 7
- Coagulation studies (PT, aPTT, fibrinogen) 7
- Functional assays for:
- Antithrombin III deficiency
- Protein C deficiency
- Protein S deficiency
- Activated protein C resistance 1
- Molecular testing for Factor V Leiden mutation 1
- Antiphospholipid antibody testing:
- Lupus anticoagulant
- Anticardiolipin antibodies
- Anti-β2 glycoprotein I antibodies 1
Second-Line Tests (Based on Clinical Presentation)
- Prothrombin gene mutation (G20210A) 6
- Homocysteine levels 6
- Factor VIII levels 6
- D-dimer and other markers of activation 5
- Flow cytometry for platelet surface glycoproteins if platelet-mediated thrombosis is suspected 7
Important Considerations for Testing
Timing of Testing
- Avoid testing during acute thrombosis as results may be inaccurate or difficult to interpret 3
- Defer testing until patient is stable and preferably not on anticoagulants 3
- For patients on anticoagulation, certain tests (protein C, protein S, antithrombin) should be postponed until therapy is completed or temporarily discontinued 6
Interpretation Pitfalls
- Multiple defects may coexist and contribute to thrombosis risk 3
- Acquired conditions (pregnancy, hormone therapy, liver disease) can affect test results 6
- Age and comorbidities must be considered when interpreting results 5
Management Implications
The identification of hypercoagulable states impacts management decisions:
- Duration of anticoagulation may be extended for patients with inherited thrombophilias after a first thrombotic event 1
- Prophylactic anticoagulation should be considered during high-risk situations (surgery, pregnancy, immobilization) for patients with known thrombophilias 1
- Specialized treatment approaches may be needed for certain conditions (e.g., AT-III or protein C concentrates for respective deficiencies) 1
- Family screening may be warranted when inherited disorders are identified 6
Common Pitfalls to Avoid
- Indiscriminate testing in patients with provoked VTE and clear precipitating factors
- Over-interpretation of borderline results without clinical correlation
- Failure to repeat abnormal tests to confirm findings
- Testing during acute thrombosis or while on anticoagulation without accounting for these effects
- Neglecting comprehensive clinical assessment before ordering specialized tests
By following these guidelines for hypercoagulability workup, clinicians can identify patients at risk for recurrent thrombosis and implement appropriate preventive strategies to reduce morbidity and mortality.