What does a hypercoagulable workup include?

Components of a Hypercoagulable Workup

A comprehensive hypercoagulable workup should include testing for both inherited and acquired thrombophilias, with specific tests selected based on the clinical context and suspected etiology of thrombosis. 1

Inherited Thrombophilia Testing

Genetic Tests

• Factor V Leiden mutation (G1691A) - Most common inherited thrombophilia, responsible for 90-95% of activated protein C resistance cases 1
• Prothrombin gene mutation (G20210A) - Present in 1-2% of general population, increases thrombotic risk 1
• JAK2V617F mutation - Particularly important in splanchnic vein thrombosis (Budd-Chiari syndrome, portal vein thrombosis) 1

Functional Coagulation Assays

• Protein C activity/antigen - Deficiency increases thrombotic risk 1
• Protein S activity/antigen - Deficiency increases thrombotic risk 1
• Antithrombin III activity - Deficiency increases thrombotic risk 1
• Activated Protein C resistance - Functional test that can detect Factor V Leiden 1

Acquired Thrombophilia Testing

Antiphospholipid Antibody Panel

• Lupus anticoagulant - More specific test for antiphospholipid syndrome 2
• Anticardiolipin antibodies (IgG, IgM, IgA) - More prevalent but less specific 2
• Beta-2 glycoprotein I antibodies - Associated with increased thrombotic risk 1

Other Tests

• Homocysteine levels - Elevated levels associated with both venous and arterial thrombosis 2
• Factor VIII levels - Elevated levels associated with thrombotic risk 2
• von Willebrand factor (vWF) levels - Elevated levels may contribute to thrombotic risk 2

Important Testing Considerations

Timing of Testing

• Perform testing at least 3 months after acute thrombotic event 1
• Wait at least 2 weeks after discontinuing oral anticoagulant therapy 1
• Direct oral anticoagulants (DOACs) can interfere with several thrombophilia tests, particularly:
  • Antithrombin activity assays
  • Coagulation-based tests for proteins C and S 1

Clinical Context for Testing

• Testing is most appropriate for:
  • Patients with VTE under age 50
  • Patients with unprovoked or recurrent VTE
  • Patients with thrombosis at unusual sites (cerebral, splanchnic, portal veins)
  • Patients with strong family history of thrombosis
  • Women with VTE history considering oral contraceptives or pregnancy 1, 2

Limitations and Caveats

• A single negative test does not completely rule out thrombophilia 1

• Random screening of the general population is not recommended due to limited cost-effectiveness 1

• Some tests (particularly functional assays) may be affected by:

  • Acute thrombosis
  • Anticoagulation therapy
  • Liver disease
  • Pregnancy
  • Inflammatory states 1

• Hypercoagulable states are more strongly associated with venous thromboembolism than arterial thrombosis 2

• About half of VTE episodes in patients with inherited thrombophilias occur in relation to predisposing events such as surgery, pregnancy, or immobilization 3

Clinical Application

The hypercoagulable workup should be tailored based on the clinical presentation. For example, patients with Budd-Chiari syndrome or portal vein thrombosis should be tested for both inherited and acquired thrombophilias, including JAK2V617F mutation 1. The results of thrombophilia testing may impact decisions regarding the duration of anticoagulation therapy, though clinical risk factors often take precedence over laboratory findings 1.

Remember that a comprehensive approach is necessary, as most thrombotic episodes occur with an additive combination of acquired and inherited predisposing factors 4.