From the Guidelines
The workup for hypercoagulability should begin with a thorough clinical history and physical examination, followed by laboratory testing based on the patient's presentation and risk factors. Initial laboratory tests should include complete blood count, prothrombin time, activated partial thromboplastin time, and D-dimer. For suspected inherited thrombophilias, specific tests include factor V Leiden mutation, prothrombin G20210A mutation, protein C and S deficiency, antithrombin deficiency, and hyperhomocysteinemia. For acquired hypercoagulable states, testing should include antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies, and anti-β2 glycoprotein I), JAK2 mutation for myeloproliferative disorders, and paroxysmal nocturnal hemoglobinuria screening.
Key Considerations
- Timing of testing is crucial; acute thrombosis, pregnancy, and certain medications can affect results, so testing should ideally occur at least 2-3 months after an acute event and after anticoagulation is temporarily discontinued when safe.
- Genetic counseling should be considered for patients with inherited thrombophilias.
- The rationale for this comprehensive approach is that hypercoagulability can result from multiple inherited and acquired factors that disrupt the balance between procoagulant and anticoagulant mechanisms, leading to increased thrombosis risk, as noted in studies such as 1 and 1.
Laboratory Tests
- Complete blood count
- Prothrombin time
- Activated partial thromboplastin time
- D-dimer
- Factor V Leiden mutation
- Prothrombin G20210A mutation
- Protein C and S deficiency
- Antithrombin deficiency
- Hyperhomocysteinemia
- Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies, and anti-β2 glycoprotein I)
- JAK2 mutation for myeloproliferative disorders
- Paroxysmal nocturnal hemoglobinuria screening
Clinical Guidance
Guidelines from reputable sources such as the American Heart Association 1 and the European Society of Cardiology 1 provide recommendations for the diagnosis and management of hypercoagulability and venous thromboembolism. These guidelines emphasize the importance of a comprehensive approach to diagnosis and treatment, taking into account the patient's individual risk factors and clinical presentation.
From the Research
Workup for Hypercoagulability
The workup for hypercoagulability involves a thorough patient history and complete physical examination to identify potential predisposing factors for thromboembolic events 2.
Clinical Assessment
Clinical assessment is used to guide the clinical laboratory evaluation for a potential hypercoagulable state, and identification of a specific hypercoagulable state is crucial for prognosis and therapeutic management 2.
Laboratory Evaluation
Laboratory testing for hypercoagulable disorders includes tests for:
- Antithrombin III, protein C, and protein S deficiencies
- Fibrinolytic disorders such as decreased plasminogen levels and plasminogen activator deficiency
- Antiphospholipid syndromes such as anticardiolipin antibody and lupus anticoagulants 3
- Other secondary and recently investigated hypercoagulable disorders, including heparin-associated thrombocytopenia, homocystinemia, lipoprotein (a), plasminogen activator inhibitor, and factor V Leiden 3
Approach to Testing
Testing for thrombophilias should be guided by the clinical presentation, suspected pathophysiology, and an understanding of how such results may affect patient care 4.
Considerations
Individuals are best tested when they are not taking anticoagulants, and laboratory testing undertaken at the time of acute thrombosis is often inaccurate or difficult to interpret 5.
Risk Factors
Risk factors that further increase clotting include obesity, recent surgery, pregnancy, and cancer, and asymptomatic individuals with underlying hypercoagulability may not require treatment except in clot-promoting situations such as trauma, pregnancy, recent surgery, or use of venous access devices 5.
Hypercoagulable States
Hypercoagulable states can be primary (inherited) or secondary (acquired), and patients with recurrent thrombosis without recognizable predisposing factors are considered to have hypercoagulable states 6.