What is the recommended dose of alteplase (tissue plasminogen activator) for thrombolysis in a patient with acute ischemic stroke?

Thrombolysis Dose in Acute Ischemic Stroke

The recommended dose of alteplase for acute ischemic stroke is 0.9 mg/kg (maximum 90 mg total), with 10% given as an intravenous bolus over 1 minute, followed by the remaining 90% infused over 60 minutes. 1, 2

Dosing Protocol

• Total dose: 0.9 mg/kg body weight, with an absolute maximum of 90 mg regardless of patient weight 1, 2
• Initial bolus: 10% of the calculated total dose administered intravenously over 1 minute 1, 2
• Continuous infusion: The remaining 90% infused over 60 minutes 1, 2

Dose Calculation Example

• For a 70 kg patient: 70 kg × 0.9 mg/kg = 63 mg total dose 2
• Bolus: 6.3 mg over 1 minute 2
• Infusion: 56.7 mg over 60 minutes 2

Time Window for Administration

Within 0-3 hours: Strong recommendation (Grade 1A) for IV alteplase administration 1, 2

Within 3-4.5 hours: Conditional recommendation (Grade 2C) for IV alteplase administration, with evidence showing improved clinical outcomes (52.4% favorable outcome vs 45.2% with placebo) 1, 3

Beyond 4.5 hours: IV alteplase is contraindicated (Grade 1B) in the standard population 1, 2

Extended Time Window Exceptions

• Wake-up stroke or unclear onset >4.5 hours: Consider IV alteplase if MRI shows DWI-FLAIR mismatch, administered within 4.5 hours of symptom recognition 1
• 4.5-9 hours with imaging selection: Consider alteplase in patients with CT or MRI core/perfusion mismatch when mechanical thrombectomy is not indicated or planned 1

Critical Pre-Treatment Requirements

Blood pressure control: BP must be lowered to <185/110 mm Hg before initiating alteplase; if this cannot be achieved, alteplase is absolutely contraindicated 1, 2

Glucose assessment: Only blood glucose measurement must precede alteplase initiation in all patients; hypoglycemia (<60 mg/dL or 3.3 mmol/L) should be treated with IV dextrose 1

Brain imaging: Non-contrast CT or MRI must exclude intracranial hemorrhage before treatment 1

Laboratory tests: Obtain CBC, electrolytes, creatinine, INR, PTT, and troponin, but do NOT delay alteplase administration for these results 1

Post-Administration Monitoring

• Blood pressure monitoring: Every 15 minutes during infusion and for 2 hours after, then every 30 minutes for 6 hours, then hourly for 16 hours 2
• Target BP: Maintain <180/105 mm Hg during and after treatment 2
• 24-hour imaging: Perform CT scan 24 hours post-thrombolysis to exclude intracranial hemorrhage before starting antiplatelet therapy 1, 2
• Antiplatelet delay: Do NOT administer aspirin or other antiplatelet agents until 24 hours after alteplase and after excluding hemorrhage on follow-up imaging 1, 2

Expected Hemorrhage Risk

The symptomatic intracranial hemorrhage rate is 2.4-7.0% with alteplase compared to 0.2-0.6% with placebo 3, 4. This risk is substantially elevated in patients on anticoagulation, with baseline rates of 4-6% in properly selected patients 2. Despite this increased hemorrhage risk, mortality does not differ significantly between alteplase and placebo groups (7.7% vs 8.4%) 3.

Critical Contraindications and Pitfalls

Anticoagulation: Patients on direct oral anticoagulants (DOACs) like apixaban should NOT receive alteplase as routine practice due to substantially elevated bleeding risk; standard coagulation tests (PT/INR, aPTT) do not reliably measure DOAC levels 2, 5

Mechanical thrombectomy: Eligible patients should receive IV alteplase even if mechanical thrombectomy is being considered; do NOT wait to evaluate response to alteplase before proceeding with catheter angiography 1

Dosing errors: The dose is weight-based with a maximum of 90 mg total—exceeding this maximum substantially increases hemorrhage risk 2

Time is critical: Earlier treatment provides greater benefit, with odds ratio of 2.11 for treatment within 90 minutes versus 1.69 for 90-180 minutes 2