What is the workup for hypercoagulability?

Workup for Hypercoagulability

The comprehensive workup for hypercoagulability should include testing for both inherited and acquired thrombophilic factors, with specific focus on factor V Leiden mutation, prothrombin G20210A gene variant, protein C and S deficiency, antithrombin deficiency, antiphospholipid antibodies, and JAK2V617F mutation. 1

Initial Assessment

When evaluating a patient for hypercoagulability, focus on:

• History of unprovoked venous or arterial thrombosis
• Thrombosis at unusual sites (e.g., portal, mesenteric, cerebral veins)
• Recurrent thrombotic events
• Family history of thrombosis
• Thrombosis at young age (<50 years)
• Pregnancy-associated thrombosis
• Thrombosis while on hormonal therapy

Laboratory Testing Algorithm

First-tier Testing (Core Panel):

• Complete blood count with peripheral smear
• Prothrombin time (PT) and activated partial thromboplastin time (aPTT)
• Factor V Leiden mutation
• Prothrombin G20210A gene variant
• Protein C activity
• Protein S activity
• Antithrombin activity
• Antiphospholipid antibodies:
  • Lupus anticoagulant
  • Anti-cardiolipin antibodies
  • Anti-β2 glycoprotein I antibodies

Second-tier Testing (Based on Clinical Suspicion):

• JAK2V617F mutation (for suspected myeloproliferative neoplasms) 1
• Calreticulin mutation (if JAK2V617F negative but MPN still suspected)
• Flow cytometry for paroxysmal nocturnal hemoglobinuria (PNH)
• Homocysteine levels
• Fibrinogen levels and function
• Factor VIII levels
• D-dimer and fibrin degradation products

Special Considerations

Timing of Testing

• Ideally perform testing when patient is not on anticoagulation
• If testing during acute thrombosis or while on anticoagulation, interpret results with caution
• For antiphospholipid antibodies, positive results should be confirmed after 12 weeks 1

Site-Specific Thrombosis Workup

• For splanchnic vein thrombosis (portal, mesenteric):

  • Always test for JAK2V617F mutation even with normal blood counts 1
  • Consider bone marrow biopsy if JAK2V617F and calreticulin mutations are negative
  • Evaluate for local factors (abdominal inflammatory conditions, malignancies) 1

• For arterial thrombosis:

  • Focus on antiphospholipid antibodies
  • Consider myeloproliferative disorders
  • Evaluate for cardiovascular risk factors

Limitations of Testing

• Acute thrombosis can cause temporary decreases in protein C, protein S, and antithrombin
• Anticoagulant therapy can affect test results:
  • Warfarin decreases protein C and S levels
  • Heparin affects antithrombin assays
  • DOACs can interfere with coagulation-based assays

Pitfalls to Avoid

1. Incomplete testing: Finding one abnormality should not deter from looking for additional risk factors 1

2. Poor timing: Testing during acute thrombosis or while on anticoagulation may yield false results

3. Overreliance on routine coagulation tests: Normal PT/INR and aPTT do not rule out hypercoagulability 1

4. Failure to repeat positive tests: Particularly for antiphospholipid antibodies, which require confirmation after 12 weeks

5. Missing acquired causes: Always evaluate for underlying conditions like malignancy, pregnancy, or inflammatory disorders

Special Patient Populations

Patients with Cirrhosis

Despite elevated INR, patients with cirrhosis may be hypercoagulable. Standard coagulation tests are poor predictors of thrombotic risk in these patients 1. Consider specialized testing such as thrombin generation assays or viscoelastic tests.

Pregnant Patients

Pregnancy is a hypercoagulable state with increased risk of thrombosis. Viscoelastic tests like TEG/ROTEM may detect pregnancy-associated hypercoagulability better than conventional tests 1.

Cancer Patients

Cancer patients have a high risk of thrombosis. Testing should focus on acquired factors and monitoring for recurrent events rather than inherited thrombophilia.

By following this systematic approach to hypercoagulability testing, clinicians can efficiently identify underlying causes of thrombosis and guide appropriate management decisions to reduce morbidity and mortality from thrombotic events.