What blood tests are used to evaluate for hypercoagulability?

Blood Tests for Hypercoagulability Evaluation

The first-line laboratory evaluation for hypercoagulability should include prothrombin time (PT), activated partial thromboplastin time (aPTT), complete blood count, fibrinogen level, and specific thrombophilia testing for Factor V Leiden mutation, prothrombin gene mutation, protein C activity, protein S activity, antithrombin III activity, lupus anticoagulant, anticardiolipin antibodies, and beta-2 glycoprotein antibodies. 1

First-Line Testing

Basic Coagulation Panel

• PT/INR: Evaluates extrinsic pathway and common pathway
• aPTT: Evaluates intrinsic pathway and common pathway
• Complete blood count (CBC): Assesses platelet count and function
• Fibrinogen level: Evaluates clotting factor adequacy

Specific Thrombophilia Testing

• Genetic testing:

  • Factor V Leiden mutation
  • Prothrombin gene mutation (G20210A)

• Functional assays:

  • Protein C activity
  • Protein S activity
  • Antithrombin III activity

• Antiphospholipid antibody testing:

  • Lupus anticoagulant
  • Anticardiolipin antibodies
  • Beta-2 glycoprotein antibodies

Second-Line Testing

For patients with abnormal initial results or high clinical suspicion despite normal first-line testing:

• Homocysteine levels: Elevated in hyperhomocysteinemia
• Factor VIII activity: Elevated levels associated with thrombosis
• JAK2 mutation: For suspected myeloproliferative disorders
• Paroxysmal nocturnal hemoglobinuria (PNH) screen
• D-dimer: Marker of active thrombosis and fibrinolysis

Advanced Testing Options

Viscoelastic Testing

• Thromboelastography (TEG) or Rotational Thromboelastometry (ROTEM): Provides comprehensive assessment of clot formation, strength, and dissolution 2
  • Parameters measured include:
    • Clot formation time
    • Maximum clot firmness
    • Clot lysis

Thrombin Generation Assay

• Assesses overall functionality of the hemostatic system
• Useful for diagnosing hyper- and hypocoagulability states 2

Clot Waveform Analysis

• Evaluates transmittance or absorbance changes during coagulation
• Parameters include clotting time, maximum coagulation velocity, and acceleration 2

Special Considerations

Timing of Testing

• For patients on anticoagulants (especially direct oral anticoagulants like apixaban), testing should be delayed until after a washout period:
  • At least 48 hours off medication
  • Consider 72+ hours for patients with renal impairment 1

Interpretation Challenges

• Acute phase reactions can affect protein C, protein S, and antithrombin levels
• Pregnancy and hormonal therapy can alter coagulation test results
• Recent thrombosis may temporarily deplete natural anticoagulants

Clinical Approach Algorithm

1. Determine clinical context:

   • Unprovoked venous thromboembolism
   • Arterial thrombosis
   • Recurrent pregnancy loss
   • Family history of thrombosis

2. Order appropriate first-line tests based on clinical suspicion

3. Interpret results in clinical context:

   • Abnormal PT/INR: Consider vitamin K deficiency, liver disease, or factor VII deficiency
   • Abnormal aPTT: Consider factor deficiencies, lupus anticoagulant, or heparin effect
   • Abnormal thrombophilia testing: Evaluate for inherited or acquired conditions

4. Proceed to second-line testing if first-line results are inconclusive or normal despite high clinical suspicion

Common Pitfalls to Avoid

• Testing during acute thrombosis can lead to falsely low levels of natural anticoagulants
• Failure to consider the effect of anticoagulants on test results
• Not documenting timing of sample collection relative to last anticoagulant dose
• Overlooking the need for repeat testing to confirm abnormal results

By following this structured approach to hypercoagulability testing, clinicians can effectively identify underlying thrombophilic conditions and guide appropriate management to reduce morbidity and mortality from thrombotic events.