From the Guidelines
A hypercoagulable state workup should include a comprehensive panel of tests, including complete blood count (CBC), prothrombin time (PT) and activated partial thromboplastin time (aPTT), fibrinogen level, D-dimer, factor V Leiden mutation, prothrombin G20210A mutation, protein C and protein S levels, antithrombin III activity, lupus anticoagulant, anticardiolipin antibodies, beta-2 glycoprotein I antibodies, and homocysteine level, as these tests help identify both inherited and acquired thrombophilias, which is crucial for reducing morbidity, mortality, and improving quality of life 1.
When evaluating a patient for a hypercoagulable state, it is essential to consider the potential causes of thrombosis, including inherited defects such as factor V Leiden, prothrombin gene mutations, antithrombin III deficiency, and deficiencies of protein C and protein S, as well as acquired conditions such as antiphospholipid syndrome, pregnancy, oral contraceptive use, estrogen therapy, malignancy, stroke with extremity paresis, trauma, surgery, or immobility 1.
Some key points to consider when ordering these tests include:
- The tests should be performed at least 2-3 months after an acute thrombotic event and, ideally, when the patient is not on anticoagulation therapy.
- If anticoagulation cannot be stopped, interpret results cautiously as some tests (particularly protein C, protein S, and antithrombin III) may be affected.
- Additional tests may include JAK2 mutation analysis and paroxysmal nocturnal hemoglobinuria (PNH) flow cytometry, depending on clinical suspicion.
- The incidence of venous thrombosis is about 1 per 1,000 person-years and leads to 50,000 deaths annually, making early identification and management of these conditions crucial for reducing morbidity and mortality 1.
By prioritizing the identification and management of hypercoagulable states, clinicians can significantly improve patient outcomes, reduce the risk of recurrent thrombotic events, and enhance overall quality of life 1.
From the Research
Hypercoagulable State Workup
The workup for a hypercoagulable state involves a combination of laboratory tests and clinical evaluation to identify underlying conditions that may be contributing to an increased risk of thrombosis.
- Patients with a family history of thrombosis, early-onset or recurring thrombosis, thrombosis at unusual sites, or warfarin-induced skin necrosis should be investigated for a possible underlying inherited hypercoagulable disorder 2.
- The evaluation should include determinations of prothrombin time (PT) and partial thromboplastin time (PTT), platelet count, antithrombin III, protein C, free protein S and total protein S levels, along with platelet aggregometry 3.
- Functional assays are more useful than immunologic assays for diagnosing AT-III deficiency, protein C and S deficiencies, and APC resistance 2.
- Testing for the antiphospholipid syndrome involves assays for the lupus anticoagulant and anticardiolipin antibodies 2.
- A molecular probe is now available for the abnormal factor V most often responsible for APC resistance 2.
Conditions to be Considered
The workup should consider both inherited and acquired hypercoagulable states, including:
- Inherited disorders such as antithrombin III deficiency, protein C and protein S deficiency, abnormalities of the fibrinolytic system, and dysfibrinogenemias 4.
- Acquired disorders such as malignancy, pregnancy, use of oral contraceptives, myeloproliferative disorders, hyperlipidemia, diabetes mellitus, and abnormalities of blood vessels and rheology 4.
- Other conditions such as the antiphospholipid syndrome, an acquired disorder 2.
Approach to Testing
The approach to testing should be guided by the clinical presentation, suspected pathophysiology, and an understanding of how such results may affect patient care 5.