What is the risk of thrombolysis (intravenous clot dissolution) with alteplase (tissue plasminogen activator) for acute ischemic stroke after pretreatment with aspirin (acetylsalicylic acid) 300 mg?

Risk of Thrombolysis for Stroke After Pretreatment with Aspirin 300 mg

Aspirin 300 mg given as pretreatment before thrombolysis increases the risk of symptomatic intracranial hemorrhage (SICH) without improving clinical outcomes, and current guidelines recommend delaying aspirin until 24 hours after alteplase administration. 1

Hemorrhagic Risk with Aspirin Pretreatment

The key evidence comes from the ARTIS trial, which demonstrated that early aspirin administration (300 mg IV within 90 minutes of alteplase) significantly increased SICH:

• SICH occurred in 4.3% of aspirin-treated patients versus 1.6% in standard treatment (absolute increase of 2.8%, p=0.04) 1
• SICH was more often the cause of poor outcome in the aspirin group compared to standard treatment (11 vs 1 patient, p=0.006) 1
• Early neurological deterioration due to SICH was 3.73 times more likely with aspirin (95% CI 1.03-13.49) 2

Importantly, this increased bleeding risk occurred without any benefit in functional outcomes:

• No improvement in favorable outcome at 3 months (54.0% aspirin vs 57.2% standard treatment, p=0.42) 1
• No evidence of early antithrombotic benefit from adding aspirin to thrombolysis 2

Current Guideline Recommendations

Multiple high-quality guidelines consistently recommend against aspirin administration immediately before or concurrent with thrombolysis:

• The American College of Chest Physicians recommends early aspirin (160-325 mg) within 48 hours for acute ischemic stroke, but this is for patients NOT receiving thrombolysis 3
• For patients receiving IV alteplase, antiplatelet agents should be delayed until after the 24-hour post-thrombolysis scan has excluded intracranial hemorrhage 3
• The standard practice is to start oral antiplatelet therapy 24 hours after alteplase treatment 1

Observational Data on Aspirin Pretreatment

Patients who were already taking aspirin before stroke onset (chronic use) also show increased bleeding risk with thrombolysis:

• Pretreatment with aspirin monotherapy increases the bleeding risk of alteplase in both observational and randomized trials with no effect on clinical outcome 4
• The risk of intracerebral hemorrhage is further increased with the combination of aspirin and clopidogrel 4

Clinical Context: When Aspirin 300 mg May Be Given

The only scenario where aspirin 300 mg near the time of thrombolysis is considered acceptable is for mechanical thrombectomy:

• Aspirin 300 mg given as standard acute stroke treatment (160-300 mg within 24-48 hours) is not a contraindication for mechanical thrombectomy 5
• This reflects that mechanical thrombectomy has different risk-benefit considerations than IV thrombolysis 5

Practical Management Algorithm

For patients presenting with acute ischemic stroke who are candidates for IV thrombolysis:

1. Do NOT administer aspirin 300 mg before or during alteplase infusion 1
2. Withhold aspirin for 24 hours after alteplase administration 3, 1
3. Obtain CT scan at 24 hours post-thrombolysis to exclude hemorrhage 3
4. Start aspirin 160-325 mg only after hemorrhage is excluded 3

For patients already on chronic aspirin who present for thrombolysis:

• Proceed with thrombolysis but counsel about slightly increased bleeding risk 4
• The increased risk is modest with aspirin monotherapy but more substantial with dual antiplatelet therapy 4

Common Pitfalls to Avoid

The most critical error is administering aspirin too early based on general stroke guidelines without recognizing the thrombolysis-specific contraindication:

• General acute stroke guidelines recommend aspirin 160-325 mg within 48 hours, but this explicitly excludes patients receiving thrombolysis 3
• The 24-hour delay is not arbitrary—it is based on the ARTIS trial showing harm with earlier administration 1
• Even if aspirin might theoretically prevent reocclusion after thrombolysis, the trial data show this benefit does not materialize while bleeding risk increases 1, 2