Can TPA Be Given After Full-Dose Aspirin?
Yes, TPA can be administered to patients who have taken aspirin prior to their acute ischemic stroke, though it carries a modestly increased risk of symptomatic intracranial hemorrhage that is outweighed by the substantial mortality and functional outcome benefits of thrombolysis.
Evidence for TPA Administration Despite Prior Aspirin Use
The most definitive evidence comes from a large observational study of 85,072 patients treated with IV tPA, where 45.7% were on antiplatelet therapy before their stroke 1. This study demonstrated:
- Increased bleeding risk: Patients on prior aspirin had higher odds of symptomatic intracranial hemorrhage (adjusted OR 1.18; absolute increase of 0.68%; number needed to harm = 147) 1
- Better functional outcomes: Despite the bleeding risk, these patients had significantly better outcomes including greater likelihood of independent ambulation (adjusted OR 1.13; number needed to treat = 43) and better modified Rankin Scale scores (adjusted OR 1.14; number needed to treat = 50) 1
- No difference in mortality: Risk-adjusted in-hospital mortality was identical between groups (adjusted OR 1.00) 1
An earlier analysis from ECASS II confirmed that aspirin use before thrombolysis increases the risk of parenchymal hemorrhage and symptomatic intracranial hemorrhage, particularly in older patients 2. However, prior aspirin use is not listed as an absolute contraindication to TPA administration in any major guideline 3.
Clinical Decision Algorithm
Step 1: Confirm TPA Eligibility
- Symptom onset within 4.5 hours 3
- Brain imaging excludes intracranial hemorrhage 3
- No absolute contraindications present 3
Step 2: Assess Aspirin-Related Risk Factors
Higher risk patients (consider more carefully but do not exclude):
- Age >75 years 2
- Extensive early ischemic changes on CT 2
- Congestive heart failure 2
- Dual antiplatelet therapy (aspirin + clopidogrel increases symptomatic ICH risk with adjusted OR 1.47; absolute increase 1.67%; number needed to harm = 60) 1
Step 3: Proceed with TPA
The net clinical benefit strongly favors treatment 1. The absolute increase in symptomatic intracranial hemorrhage (0.68% for aspirin alone, 1.67% for dual antiplatelet therapy) is substantially outweighed by the proven mortality reduction (18-50%) and functional benefit from thrombolysis 4.
Post-TPA Management for Aspirin-Exposed Patients
Critical timing requirements 3, 5, 4:
- Hold all antiplatelet agents for 24 hours after TPA administration 3
- Obtain brain imaging at 24 hours to exclude intracranial hemorrhage 3, 4
- Monitor extremely closely for neurological deterioration in the first 24 hours 4
- Resume aspirin only after the 24-hour scan confirms no hemorrhage 3, 4
Common Pitfalls to Avoid
Do not withhold TPA solely based on prior aspirin use - this represents a relative risk factor requiring risk-benefit analysis, not an absolute contraindication 4. The American College of Chest Physicians explicitly recommends IV r-tPA within 3 hours (Grade 1A) and suggests it within 3-4.5 hours (Grade 2C) without excluding patients on prior aspirin 3.
Do not restart aspirin immediately after TPA - the American Heart Association and Canadian Stroke Best Practice guidelines both emphasize waiting the full 24 hours with confirmatory imaging before resuming any antiplatelet therapy 3, 5, 4.
Do not confuse with aspirin given concurrently - while aspirin should not be administered within 24 hours of thrombolytic therapy (Class III recommendation), prior aspirin use before stroke onset is a different clinical scenario 3, 5, 4.
Alternative Consideration
For patients on dual antiplatelet therapy (aspirin + clopidogrel) where the bleeding risk is highest (NNH = 60), mechanical thrombectomy may be considered as an alternative, as recent aspirin is not a contraindication for endovascular therapy 4. However, this should not delay TPA administration in eligible patients, as the functional benefits still outweigh risks even in this higher-risk subgroup 1.