What tests should be included in a hypercoagulable (coagulation disorder) panel to work up a patient with pulmonary embolism?

Hypercoagulable Panel for Pulmonary Embolism Workup

Laboratory evaluation for thrombophilia in patients with pulmonary embolism should include testing for activated Protein C resistance and/or Factor V Leiden, Prothrombin gene mutation, antithrombin, Protein C, and Protein S deficiencies, lupus anticoagulant, anticardiolipin antibodies, anti-β2-glycoprotein-1 antibodies, and Factor VIII levels. 1

When to Order Thrombophilia Testing

Thrombophilia testing is not recommended for all patients with pulmonary embolism. Testing should be considered in the following specific scenarios:

• Young patients (<50 years)
• Unprovoked (idiopathic) PE
• Recurrent thrombotic events
• Unusual site thrombosis
• Strong family history of VTE
• Pregnancy-related thrombosis
• PE despite adequate anticoagulation

Components of a Hypercoagulable Panel

Hereditary Thrombophilias

1. Factor V Leiden mutation (R506Q) - Most common hereditary thrombophilia in white populations 1
2. Prothrombin gene mutation (G20210A) - Second most common hereditary thrombophilia 1
3. Protein C deficiency - Natural anticoagulant deficiency
4. Protein S deficiency - Natural anticoagulant deficiency
5. Antithrombin deficiency - Most thrombogenic of the hereditary thrombophilias

Acquired Thrombophilias

1. Antiphospholipid antibody syndrome:
   • Lupus anticoagulant
   • Anticardiolipin antibodies
   • Anti-β2-glycoprotein-1 antibodies 1
2. Elevated Factor VIII levels 1

Timing of Testing

The timing of testing is critical for accurate results:

• Acute phase testing limitations: Protein C, Protein S, and antithrombin levels may be falsely decreased during acute thrombosis
• Anticoagulation effects: Vitamin K antagonists decrease Protein C and S levels
• Optimal timing: Testing should ideally be performed:
  • After completion of anticoagulation therapy (at least 2-4 weeks after discontinuation)
  • If testing must be done while on anticoagulation, interpret results with caution

Special Considerations

Hypercoagulable States in Specific Populations

For patients with suspected antiphospholipid antibody syndrome, the British Thoracic Society guidelines recommend indefinite anticoagulation with vitamin K antagonists 1. This is particularly important as antiphospholipid syndrome is associated with a high risk of recurrent thrombosis.

Limitations of Testing

It's important to recognize that:

• Many patients with PE have multiple thrombophilic risk factors acting synergistically 1
• Up to 50% of patients with genetic predisposition to thrombosis may have other contributing factors 1
• Negative testing does not rule out an underlying thrombophilic state

Clinical Application

When evaluating a patient with PE for possible thrombophilia:

1. First assess for acquired risk factors (surgery, immobilization, cancer, etc.)
2. Consider thrombophilia testing primarily in patients with unprovoked PE or those with features suggesting hereditary thrombophilia
3. Time the testing appropriately to avoid false results
4. Interpret results in the context of the clinical scenario

Common Pitfalls to Avoid

1. Indiscriminate testing - Testing all patients with PE is not cost-effective and may lead to unnecessary anxiety and prolonged anticoagulation
2. Testing during acute thrombosis - May lead to falsely abnormal results
3. Testing while on anticoagulation - Warfarin affects Protein C and S levels; heparin affects antithrombin levels
4. Overreliance on results - Management decisions should not be based solely on thrombophilia testing

The results of thrombophilia testing may influence the duration of anticoagulation therapy, particularly in patients with unprovoked PE who test positive for high-risk thrombophilias such as antiphospholipid syndrome, which requires indefinite anticoagulation 1.