What initial blood work is recommended for a patient suspected of having a hypercoagulable state?

Initial Blood Work for Hypercoagulable State Evaluation

For patients suspected of having a hypercoagulable state, the recommended initial blood work should include complete blood count (CBC), prothrombin time (PT), activated partial thromboplastin time (aPTT), and specific factor assays including factor VIII, protein C, protein S, and antithrombin III levels. 1

First-Line Laboratory Testing

The initial laboratory evaluation for suspected hypercoagulable states should include:

• Basic coagulation panel:

  • Complete blood count (CBC)
  • Prothrombin time (PT)
  • Activated partial thromboplastin time (aPTT)
  • Fibrinogen level (Clauss method)

• Factor assays:

  • Factor VIII, IX, and XI levels
  • Von Willebrand factor (VWF) antigen (VWF:Ag)
  • VWF ristocetin cofactor activity (VWF:RCo)

• Natural anticoagulant assessment:

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

• Additional tests:

  • ABO blood group (influences VWF levels)
  • D-dimer

According to the International Society on Thrombosis and Haemostasis (ISTH) guidelines, these tests are considered first-line investigations in the evaluation of potential bleeding disorders and hypercoagulable states 1. The complete panel provides a comprehensive assessment of both the intrinsic and extrinsic coagulation pathways.

Second-Line Testing

If first-line testing is normal but clinical suspicion remains high, consider these second-line tests:

• Factor V Leiden mutation
• Prothrombin gene mutation (G20210A)
• Antiphospholipid antibodies (anticardiolipin, lupus anticoagulant)
• Homocysteine levels
• Factor II, V, VII, X, and XIII levels
• Thrombin generation assay
• Genetic testing for inherited thrombophilias

According to guidelines, approximately 48% of specialists include genetic testing as a second-line investigation 1.

Clinical Context for Testing

Testing should be guided by:

• Age of the patient (younger patients have higher yield for inherited disorders)
• Family history of thrombosis
• Unprovoked or recurrent thrombotic events
• Unusual site of thrombosis (cerebral, mesenteric, portal veins)
• Thrombosis despite adequate anticoagulation

Common Pitfalls to Avoid

1. Timing of testing: Avoid testing during acute thrombotic events or while on anticoagulation therapy, as this may affect results of protein C, protein S, and antithrombin III levels.

2. Incomplete testing: Failure to order a comprehensive panel may miss important abnormalities.

3. Overinterpretation of single abnormal results: A single abnormal test should be confirmed with repeat testing.

4. Failure to consider acquired causes: Many conditions (pregnancy, malignancy, inflammatory states) can cause acquired hypercoagulability.

5. Testing all stroke patients: Guidelines do not recommend universal "hypercoagulable workups" for all stroke patients, but rather targeted testing for young patients with cryptogenic stroke or those with family history of thrombosis 2.

By following this structured approach to laboratory evaluation, clinicians can efficiently identify underlying hypercoagulable disorders and guide appropriate management to prevent recurrent thrombotic events.