Antiplatelet Therapy After Stroke with Thrombolysis (TNK/tPA)
Aspirin should be delayed until 24 hours after thrombolysis, initiated only after repeat brain imaging excludes intracranial hemorrhage, then continued indefinitely at 81-325 mg daily. 1, 2
Critical Timing: The 24-Hour Rule
All antiplatelet agents must be withheld for 24 hours after thrombolytic therapy. This is a firm, evidence-based safety requirement to minimize bleeding risk while preserving thrombolysis benefits. 1, 2
- At 24 hours post-thrombolysis: Obtain repeat brain imaging (CT or MRI) to exclude intracranial hemorrhage before initiating any antiplatelet therapy. 1
- If imaging is clear: Start aspirin 160-325 mg as a loading dose, then continue 81-325 mg daily indefinitely. 1
- If hemorrhage is present: Antiplatelet therapy remains contraindicated until the clinical situation is reassessed. 1
Dual Antiplatelet Therapy (DAPT) Considerations
For patients with minor stroke (NIHSS 0-3) or high-risk TIA, dual antiplatelet therapy with aspirin plus clopidogrel is highly effective but requires careful timing after thrombolysis:
- DAPT should only be initiated after the 24-hour safety window and after intracranial hemorrhage has been excluded on imaging. 1, 2
- Loading doses: Aspirin 160-325 mg + clopidogrel 300-600 mg, followed by aspirin 81 mg daily + clopidogrel 75 mg daily. 1, 3
- Duration: Continue DAPT for exactly 21-30 days, then transition to single antiplatelet therapy. 1, 3
- Timing caveat: DAPT is most effective when started within 12-24 hours of symptom onset in non-thrombolyzed patients, but this benefit must be balanced against bleeding risk in thrombolyzed patients. 1, 3
Long-Term Antiplatelet Strategy
After completing the acute phase (with or without DAPT):
- Continue single antiplatelet therapy indefinitely for secondary stroke prevention. 1
- Preferred agents: Clopidogrel 75 mg daily or aspirin 81-100 mg daily plus extended-release dipyridamole 200 mg twice daily are superior to aspirin monotherapy for long-term prevention. 1, 4
- Alternative: Aspirin 81-325 mg daily alone is acceptable if other agents are not tolerated. 1
Common Pitfalls to Avoid
Do not start antiplatelet therapy before the 24-hour post-thrombolysis imaging. This is the most critical error that increases symptomatic intracranial hemorrhage risk. 1, 2
Do not use dual antiplatelet therapy in moderate-to-severe strokes (NIHSS >3) after thrombolysis, as bleeding risk outweighs benefit. DAPT is only indicated for minor strokes or high-risk TIA. 1, 5
Do not continue DAPT beyond 21-30 days. Prolonged dual therapy increases major bleeding without additional benefit. 1, 5
Do not forget dysphagia screening. If the patient cannot swallow safely, use enteral tube (aspirin 80 mg daily, clopidogrel 75 mg daily) or rectal aspirin suppository (325 mg daily). 1
Special Clinical Scenarios
Patients already on antiplatelet therapy before stroke: These patients have higher rates of symptomatic intracranial hemorrhage after thrombolysis (5.0% vs 3.7% in non-users), but similar mortality and better functional outcomes. The 24-hour delay rule still applies. 6
Patients with atrial fibrillation: Anticoagulation, not antiplatelet therapy, is required for long-term secondary prevention. Transition to anticoagulation after the acute period. 1, 4
Patients with intracranial atherosclerotic stenosis: After the 24-hour safety window, these patients benefit from DAPT with aspirin plus clopidogrel for 21-90 days. 3, 4