Can I give tPA (tissue plasminogen activator) in an infarct?

tPA Administration in Acute Ischemic Stroke

tPA (tissue plasminogen activator) should be administered for acute ischemic stroke within 3 hours of symptom onset, with a possible extended window to 4.5 hours in carefully selected patients, but is contraindicated in hemorrhagic stroke or beyond the approved time windows. 1, 2

Time Window Considerations

• Strong recommendation (Grade 1A) for IV alteplase within 3 hours of symptom onset
• Conditional recommendation (Grade 2C) for IV alteplase within 3-4.5 hours of symptom onset
• Administration beyond 4.5 hours is not recommended (Grade 1B) 2

Benefit vs. Risk Analysis

Benefits:

• Within 3 hours: Increases probability of better long-term functional outcome (NNT=8; 95% CI 4 to 31) 1
• Within 3-4.5 hours: May increase probability of better long-term functional outcome (NNT=14; 95% CI 7 to 244) 1

Risks:

• Within 3 hours: Increases risk of symptomatic intracerebral hemorrhage (sICH) (NNH=17; 95% CI 12 to 34) 1
• Within 3-4.5 hours: Increases risk of sICH (NNH=23; 95% CI 13 to 78) 1
• No significant effect on 90-day mortality 1

Absolute Contraindications

• Hemorrhagic stroke (must be ruled out by CT scan)
• Time of symptom onset >4.5 hours or unknown
• Another stroke or serious head injury within preceding 3 months
• Major surgery within prior 14 days
• History of intracranial hemorrhage
• Gastrointestinal or genitourinary hemorrhage within previous 21 days 2

Administration Protocol

1. Confirm ischemic stroke diagnosis with CT scan to rule out hemorrhage
2. Verify time window (within 4.5 hours of symptom onset)
3. Check blood pressure - target ≤185/110 mmHg before initiating IV thrombolysis
4. Administer standard dose: 0.9 mg/kg (maximum 90 mg)
   • 10% as IV bolus over 1 minute
   • Remaining 90% as IV infusion over 60 minutes 2, 3
5. Monitor patient:
   • Neurological assessments every 15 minutes during infusion and for 2 hours
   • Then every 30 minutes for the next 6 hours
   • Then hourly until 24 hours after treatment 2
6. Maintain blood pressure below 180/105 mmHg during and for 24 hours after treatment 2

Post-tPA Management

• Delay aspirin administration for 24 hours after tPA 2
• Monitor for complications:
  • Angioedema: Manage with antihistamines, glucocorticoids, and airway management if needed
  • Bleeding: Individualized approach to management 2
• For immobile patients, provide VTE prophylaxis with subcutaneous heparin (preferably LMWH) 2

Special Considerations

• For patients on direct oral anticoagulants (DOACs), tPA should not be routinely administered 2
• Patients with large vessel occlusions may benefit from endovascular therapy (within 6 hours of symptom onset), which can be performed in addition to IV tPA 2

Common Pitfalls to Avoid

1. Delaying treatment - Door-to-needle time should be less than 60 minutes, with a target median of 30 minutes 2
2. Inappropriate patient selection - Carefully screen for contraindications
3. Inadequate blood pressure control - Ensure BP ≤185/110 mmHg before tPA and maintain <180/105 mmHg after
4. Administering aspirin too soon - Must wait 24 hours after tPA
5. Failure to monitor closely - Follow recommended neurological assessment schedule
6. Overlooking large vessel occlusion - Consider endovascular therapy for eligible patients

Remember that shared decision-making between the provider and patient/surrogate should include discussion of potential benefits and harms prior to administering tPA for acute ischemic stroke 1.