What laboratory tests are indicated for a patient suspected of having a hypercoagulable state?

Laboratory Workup for Hypercoagulable State

A comprehensive hypercoagulable workup should include first-line tests (complete blood count, coagulation studies, and basic thrombophilia testing) followed by second-line specialized tests based on clinical suspicion and initial results. 1

First-Line Laboratory Tests

• Complete Blood Count (CBC) with platelet count - Essential to assess for thrombocytosis or other hematologic abnormalities that may contribute to hypercoagulability 1
• Coagulation profile:
  • Prothrombin Time (PT) / International Normalized Ratio (INR) 1
  • Activated Partial Thromboplastin Time (aPTT) 1
  • Fibrinogen level 1
  • D-dimer levels 1
• Anti-PF4 antibody testing - For suspected heparin-induced thrombocytopenia, particularly in patients with recent heparin exposure 1

Second-Line Specialized Tests

Inherited Thrombophilia Testing

• Factor V Leiden mutation - Most common inherited thrombophilia 2, 3
• Prothrombin gene mutation (G20210A) - Second most common inherited thrombophilia 3
• Natural anticoagulant deficiencies:
  • Protein C activity and antigen levels 2, 3
  • Protein S activity and free antigen levels 2, 4
  • Antithrombin III activity 2, 3

Acquired Thrombophilia Testing

• Antiphospholipid antibody panel:
  • Lupus anticoagulant 1, 3
  • Anticardiolipin antibodies (IgG and IgM) 1, 3
  • Anti-β2 glycoprotein I antibodies (IgG and IgM) 1
• Homocysteine levels - Elevated levels associated with arterial and venous thrombosis 3

Additional Specialized Tests

• Functional platelet tests - When platelet-mediated hypercoagulability is suspected:
  • Platelet aggregation studies 1, 5
  • Platelet function analyzer (PFA-100/200) 1
• Thrombin generation assay - Provides global assessment of coagulation potential 1
• Fibrinolysis assays - To assess for hypofibrinolysis 1
• Flow cytometry - For specialized platelet disorders 1
• Genetic testing - For rare thrombophilias or when family history strongly suggests inherited disorder 1, 3

Testing Algorithm

1. Initial assessment:

   • Begin with CBC, PT/INR, aPTT, fibrinogen, and D-dimer in all patients 1, 6
   • If patient has history of heparin exposure with thrombocytopenia, add anti-PF4 antibody testing 1

2. For venous thromboembolism (VTE):

   • Proceed with Factor V Leiden, prothrombin gene mutation, protein C, protein S, antithrombin III, and antiphospholipid antibody panel 2, 3
   • Consider homocysteine levels, especially with arterial events or family history 3

3. For arterial thrombosis:

   • Focus on antiphospholipid antibody panel, homocysteine levels, and platelet function studies 3
   • Consider fibrinolysis assays and thrombin generation assay 1

4. For recurrent pregnancy loss or pregnancy-related thrombosis:

   • Include protein S (often decreased in pregnancy), Factor VII, Factor VIII, prothrombin fragment 1+2, and fibrinolysis markers (t-PA/PAI-1) 4

Important Considerations

• Timing of testing is critical - acute thrombosis, inflammation, pregnancy, and anticoagulant therapy can affect results 3, 4
• For patients on anticoagulation therapy, certain tests (protein C, protein S, antithrombin III) may need to be delayed until therapy is completed or specialized interpretation is required 1
• Repeat testing may be necessary to confirm abnormal results, particularly for antiphospholipid antibodies which require positive tests 12 weeks apart 1
• Functional tests for platelet activation should be considered when standard thrombophilia testing is negative but clinical suspicion remains high 1

Patient Selection for Testing

• Young patients (<50 years) with unprovoked thrombosis 3
• Patients with recurrent thrombotic events 3
• Thrombosis in unusual sites (cerebral, mesenteric, hepatic veins) 3
• Strong family history of thrombosis 2, 3
• Women with recurrent pregnancy loss or pregnancy-related thrombosis 4
• Patients with arterial thrombosis without traditional risk factors 3