What is the appropriate workup for hypercoagulability?

Workup for Hypercoagulability

The appropriate workup for hypercoagulability should include testing for prothrombin 20210A mutation, activated protein C resistance, factor VIII levels, protein C deficiency, protein S deficiency, and antithrombin III deficiency, with consultation from a thrombosis specialist recommended to guide testing and interpretation. 1

Clinical Context for Testing

Testing for hypercoagulable states should be targeted based on clinical presentation. Consider evaluation in patients with:

• Unprovoked thrombosis
• Thrombosis at unusual sites
• Recurrent thrombotic events
• Family history of thrombosis
• Thrombosis at young age (<50 years)
• Pregnancy-associated complications or spontaneous abortions
• Arterial and venous thrombosis
• Evidence of systemic hypercoagulability

First-Tier Testing

1. Basic Coagulation Panel:

   • Complete blood count with platelet count
   • Prothrombin time (PT)
   • Activated partial thromboplastin time (aPTT)
   • Fibrinogen level

2. Common Thrombophilia Tests:

   • Factor V Leiden mutation/Activated protein C resistance
   • Prothrombin G20210A mutation
   • Protein C activity/level
   • Protein S activity/level
   • Antithrombin III activity
   • Lupus anticoagulant
   • Anticardiolipin antibodies
   • Factor VIII levels

Second-Tier Testing (Based on Clinical Suspicion)

• Homocysteine levels
• Plasminogen activator inhibitor-1 (PAI-1)
• von Willebrand factor levels
• Additional genetic testing (e.g., CADASIL, Fabry's disease, MELAS) in young adults with stroke 1

Important Testing Considerations

1. Timing of Testing:

   • Protein C, protein S, and antithrombin levels should be tested at least 4-6 weeks after acute thrombosis and discontinuation of anticoagulation therapy, as these levels may be altered during acute events 1
   • Factor VIII should be tested up to 6 months after the acute event 1

2. Anticoagulation Effects:

   • Warfarin affects protein C and S levels
   • Heparin affects antithrombin III levels
   • Consider testing before starting anticoagulation or after temporary discontinuation when safe

3. Special Populations:

   • Cirrhosis patients: Standard coagulation tests like INR may not accurately reflect bleeding risk; consider thromboelastography (TEG) or rotational thromboelastometry (ROTEM) 1
   • Cushing's syndrome: Patients show activated coagulation cascade with shortened aPTT, increased fibrinogen, von Willebrand factor, and factor VIII 1
   • Stroke patients: Consider hypercoagulability testing in younger patients with stroke of unknown source despite thorough evaluation 1

Diagnostic Algorithm

1. Initial Assessment:

   • Determine if unprovoked or provoked thrombosis
   • Identify any clinical risk factors (surgery, immobilization, cancer)
   • Review family history of thrombosis

2. Laboratory Testing:

   • Order first-tier tests for all patients with suspected hypercoagulability
   • Add second-tier tests based on clinical presentation and results of first-tier tests

3. Interpretation:

   • Positive results should be confirmed with repeat testing
   • Consider consulting hematology/thrombosis specialist for interpretation and management 1

Common Pitfalls to Avoid

1. Testing during acute thrombosis or while on anticoagulation, which can lead to false results
2. Overinterpreting single abnormal values without clinical correlation
3. Failure to repeat abnormal tests for confirmation
4. Not considering multiple coexisting hypercoagulable factors, as they often occur together
5. Indiscriminate testing in patients with provoked thrombosis with clear precipitating factors

Management Implications

Identification of specific hypercoagulable states impacts:

• Duration of anticoagulation therapy
• Prophylaxis during high-risk periods
• Family screening recommendations
• Pregnancy management
• Perioperative risk assessment

In patients with ischemic stroke or TIA of unknown source who are found to have hypercoagulable states such as prothrombin mutation, activated protein C resistance, or deficiencies of protein C, S, or antithrombin III, antiplatelet therapy is reasonable to reduce recurrence risk 1.

For patients with acute arterial thrombosis and suspected hypercoagulability, immediate anticoagulation therapy is recommended while completing the diagnostic workup 1.