From the Guidelines
A hypercoagulability workup for stroke in a young person should include both laboratory testing and clinical evaluation, prioritizing the identification of inherited thrombophilias and other hypercoagulable states that may increase the risk of stroke, as recommended by the most recent guidelines 1. The workup should include initial testing such as complete blood count, comprehensive metabolic panel, lipid profile, hemoglobin A1c, and coagulation studies (PT/INR, PTT). Specific hypercoagulability tests should include:
- Factor V Leiden mutation
- Prothrombin gene mutation (G20210A)
- Protein C and S levels
- Antithrombin III activity
- Antiphospholipid antibodies (anticardiolipin antibodies, lupus anticoagulant, beta-2 glycoprotein)
- Homocysteine levels
- Methylenetetrahydrofolate reductase (MTHFR) mutation testing Additional tests to consider include JAK2 mutation for myeloproliferative disorders, fibrinogen levels, factor VIII levels, and lipoprotein(a). Timing of testing is important, as acute stroke and anticoagulation therapy can affect results; protein C, protein S, and antithrombin III should ideally be tested after the acute phase and off anticoagulation 1. Clinical evaluation should include a thorough family history of thrombotic events and assessment for other risk factors like oral contraceptive use, smoking, hypertension, and migraine with aura. This comprehensive approach is necessary because hypercoagulable states are an important but uncommon cause of stroke in young adults (under 50), and identifying a specific disorder may influence treatment decisions, including the type and duration of anticoagulation therapy, as highlighted in the 2021 guideline for the prevention of stroke in patients with stroke and transient ischemic attack 1.
From the Research
Hypercoagulable Workup for Stroke in Young Persons
- The presence of hypercoagulable states is a significant risk factor for ischemic stroke in young people, with studies suggesting that up to 46% of young stroke patients may have a hypercoagulable state 2.
- The most common hypercoagulable abnormalities found in young stroke patients include acquired hyperhomocysteinemia, protein C or S deficiency, factor V Leiden mutation, and methyl-tetrahydro-folate-reductase (MTHFR) C677T mutation 2.
- Hypercoagulable states can be inherited or acquired, with conditions such as antiphospholipid antibody syndrome, polycythemia vera, and myeloproliferative disease being common causes of acquired hypercoagulable states 3.
- The optimal treatment for thrombophilias, including hypercoagulable states, consists of oral or injectable anticoagulants, with direct thrombin inhibitors and platelet glycoprotein IIb/IIIa antagonists also being considered as attractive approaches 3.
Testing for Hypercoagulable States
- The utility of testing for hypercoagulable states in ischemic stroke is unclear, with some studies suggesting that it may be useful in certain populations, such as young stroke patients or those with a family history of thrombosis 4, 5.
- Certain tests, such as C-reactive protein, homocysteine, antiphospholipid antibodies, and lipoprotein(a), may be useful in patients with a history of stroke or at high risk for stroke, as evidenced by prospective data 5.
- Factor V Leiden, prothrombin G20210A, protein C, protein S, and antithrombin are not recommended for routine testing but may be useful in certain populations, such as in pediatric patients or in patients with cerebral vein thrombosis 5.
Management of Hypercoagulable States
- Treatment of a first stroke with a documented hypercoagulable state is typically long-term or indefinite duration warfarin, although there is a paucity of clinical trial data supporting this clinical approach 4.
- Lifetime dual antiplatelets' therapy should be used as secondary prevention of an arterial acute event (stroke, IMA or peripheral ischemia) due to hyperhomocysteinemia 3.
- A careful history, thorough examination, and methodical workup are essential in the evaluation and management of ischemic stroke in young adults, with specific management predicated on identification of the underlying etiology 6.