What blood tests should I order to rule out hypercoagulability?

Laboratory Testing for Hypercoagulable States ("Sticky Blood" Syndrome)

The initial laboratory evaluation for hypercoagulable states should include complete blood count (CBC), prothrombin time (PT), activated partial thromboplastin time (aPTT), and von Willebrand factor (VWF) panel consisting of VWF antigen, VWF ristocetin cofactor activity, and factor VIII coagulant activity. 1

First-Line Testing

The following tests should be ordered as first-line evaluation:

1. Basic Coagulation Panel:

   • Complete Blood Count (CBC) with platelet count
   • Prothrombin Time (PT)
   • Activated Partial Thromboplastin Time (aPTT)
   • Fibrinogen level

2. Von Willebrand Disease Panel:

   • VWF antigen (VWF:Ag)
   • VWF ristocetin cofactor activity (VWF:RCo)
   • Factor VIII coagulant activity (FVIII)

3. Additional First-Line Tests:

   • D-dimer
   • ABO blood group (affects VWF levels)
   • C-reactive protein (CRP)

Second-Line Testing

If first-line testing is normal but clinical suspicion remains high, proceed with:

1. Thrombophilia Testing:

   • Antithrombin activity
   • Protein C activity
   • Protein S activity
   • Factor V Leiden mutation (activated protein C resistance)
   • Prothrombin gene mutation (G20210A)
   • Lupus anticoagulant
   • Anti-cardiolipin antibodies
   • Anti-β2 glycoprotein I antibodies

2. Specialized Testing:

   • Homocysteine levels
   • Factor assays (II, V, VII, IX, X, XI)
   • Thrombin generation assay
   • Platelet function testing

Interpretation Considerations

• Timing of Testing: Ideally, testing should be performed before initiating anticoagulation therapy or at least 2-4 weeks after discontinuation of anticoagulants.
• False Positives: Acute thrombosis, inflammation, pregnancy, and certain medications can affect test results.
• False Negatives: Testing too soon after a thrombotic event may yield false-negative results for protein C, protein S, and antithrombin deficiencies.

Special Considerations

• Recent Thrombosis: If the patient has had a recent thrombotic event, certain tests (protein C, protein S, antithrombin) may be falsely low and should be repeated later.

• Anticoagulation: If the patient is on anticoagulants, interpretation of results requires caution:

  • Warfarin affects protein C and S levels
  • Heparin affects antithrombin levels and aPTT
  • DOACs can interfere with various coagulation assays

• Pregnancy: Physiologic changes during pregnancy can affect coagulation parameters, particularly protein S levels which decrease normally.

Testing Algorithm

1. Assess clinical probability of hypercoagulable state:

   • History of unprovoked thrombosis
   • Thrombosis at young age (<50 years)
   • Recurrent thrombotic events
   • Family history of thrombosis
   • Unusual site thrombosis (cerebral, mesenteric, portal veins)

2. Order first-line tests regardless of clinical probability

3. If first-line tests are normal but clinical suspicion remains high:

   • Proceed with second-line testing
   • Consider hematology consultation

4. If abnormalities are detected:

   • Confirm with repeat testing when appropriate
   • Consider family screening for inherited disorders
   • Determine need for long-term anticoagulation

Common Pitfalls to Avoid

• Overtesting: Testing asymptomatic individuals without clinical indications is not recommended.
• Timing errors: Testing during acute thrombosis or while on anticoagulation can lead to misleading results.
• Incomplete testing: Failure to order a comprehensive panel may miss important diagnoses.
• Misinterpretation: Not considering pre-analytical variables (sample handling, timing) that can affect results.

By following this structured approach to laboratory testing for hypercoagulable states, clinicians can efficiently identify underlying thrombophilic conditions and guide appropriate management decisions for patients with suspected "sticky blood" syndrome.