tPA is NOT Contraindicated in Ischemic Stroke—It is the Primary Treatment
IV tPA at 0.9 mg/kg (maximum 90 mg) is the first-line, FDA-approved treatment for acute ischemic stroke when administered within 3 hours of symptom onset, and should be offered to all eligible patients meeting NINDS criteria. 1, 2
Time-Based Treatment Algorithm
0-3 Hour Window (Strongest Evidence)
- Administer IV tPA to all eligible patients—this is a Level A/Grade 1A recommendation with the highest quality evidence. 1, 3
- This provides an absolute benefit of 12% more patients achieving minimal or no disability (NNT=8). 1, 2, 4
- The symptomatic intracranial hemorrhage (sICH) risk is 6-7% versus 1% with placebo (NNH=17). 1
- 90-day mortality is not significantly different between tPA and placebo groups (17% vs 21%). 1
3-4.5 Hour Window (Extended Window)
- Offer IV tPA to carefully selected patients meeting ECASS III criteria—this is a Level B/Grade 2C recommendation. 1, 2, 3
- This provides a smaller but meaningful benefit (NNT=14 for favorable outcome). 1, 2, 4
- The sICH risk increases to approximately 8% (NNH=23). 1, 4
- Additional ECASS III exclusion criteria apply: age >80 years, NIHSS >25, history of both diabetes and prior stroke, or patients on oral anticoagulants. 1
Beyond 4.5 Hours
- Do not administer IV tPA beyond 4.5 hours—this is a Grade 1B recommendation against use. 2, 3, 4
- Consider intraarterial thrombolysis within 6 hours for proximal cerebral artery occlusions when IV tPA is not eligible (Grade 2C). 3, 4
Absolute Contraindications (When tPA CANNOT Be Given)
Imaging Contraindications
- Intracranial hemorrhage on CT or MRI is an absolute contraindication. 1, 2
- Extensive early ischemic changes exceeding 1/3 of MCA territory is a contraindication. 2, 4
- Minor early ischemic changes (<1/3 MCA territory) are NOT a contraindication—31% of NINDS trial patients had these changes with no difference in benefit or risk. 1
Medication Contraindications
- Patients on direct oral anticoagulants (DOACs) should never receive tPA due to substantially elevated bleeding risk—this is an absolute contraindication. 2, 4
- Patients on antiplatelet therapy (aspirin, clopidogrel) CAN receive tPA at standard dosing, accepting a 3% absolute increased ICH risk. 2, 4
Blood Pressure Contraindications
- Blood pressure must be reduced to <185/110 mmHg before initiating tPA—failure to achieve this is an absolute contraindication. 2, 3, 4
- Use labetalol or nicardipine for blood pressure control. 2
Critical Implementation Details
Dosing and Administration
- Administer 0.9 mg/kg (maximum 90 mg total) with 10% given as a bolus over 1 minute and remaining 90% infused over 60 minutes. 1, 2, 4
- Treat as rapidly as possible within the chosen time window—earlier treatment provides substantially greater benefit (OR 2.11 for treatment within 90 minutes vs OR 1.69 for 90-180 minutes). 3
Post-Treatment Monitoring
- Monitor blood pressure every 15 minutes during infusion and for 2 hours after, then every 30 minutes for 6 hours, then hourly for 16 hours. 2, 3
- Maintain BP <180/105 mmHg during and after treatment. 2
- Do not give anticoagulants or antiplatelet agents for 24 hours after tPA administration. 2, 3, 4
- Initiate aspirin 160-325 mg within 24-48 hours for patients not receiving anticoagulation (Grade 1A). 2, 4
Common Pitfalls to Avoid
Do Not Exclude These Patients
- Patients with minor strokes should NOT be excluded from tPA consideration—they may still benefit significantly. 2, 3, 4
- Patients with mild to moderate strokes (NIHSS <20) and those <75 years have the greatest potential for excellent outcomes. 4
Shared Decision-Making
- Engage in shared decision-making with patients/surrogates before administering tPA, discussing both benefits (NNT=8 for 0-3 hours) and harms (NNH=17 for sICH). 1, 4
- Patients tend to overestimate benefits and underestimate harms—provide realistic expectations. 1