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

tPA Dosing for Acute Ischemic Stroke

The standard dose of tPA (alteplase) for acute ischemic stroke is 0.9 mg/kg (maximum 90 mg total), administered as 10% IV bolus over 1 minute, followed by the remaining 90% infused over 60 minutes. 1, 2

Standard Dosing Protocol

Calculate the total dose as patient weight in kg × 0.9 mg/kg, with an absolute maximum of 90 mg regardless of actual body weight. 2

• Administer 10% of the calculated total dose as an IV bolus over 1 minute 1, 2
• Infuse the remaining 90% over 60 minutes 1, 2
• For patients weighing >100 kg, cap the dose at 90 mg (effectively giving 0.82 mg/kg for a 110 kg patient) 3

Time Window Considerations

Within 0-3 hours of symptom onset: tPA should be offered to all eligible patients who meet NINDS criteria (Level A recommendation). 1

Between 3-4.5 hours of symptom onset: tPA should be considered in patients who meet ECASS III criteria (Level B recommendation). 1

• Treatment beyond 4.5 hours is contraindicated 2
• The absolute benefit is greatest when treatment is initiated earliest, with odds ratio of 2.11 for treatment within 90 minutes versus 1.69 for 90-180 minutes 2
• Every minute counts—treat as rapidly as possible once the decision is made 1

Critical Pre-Administration Requirements

Blood pressure must be reduced to <185/110 mmHg before initiating tPA, or the drug should not be given. 2

• Use labetalol or nicardipine for blood pressure control 2
• If blood pressure cannot be controlled below these thresholds, tPA is absolutely contraindicated 2
• Obtain non-contrast head CT immediately to exclude intracranial hemorrhage 2

Post-Administration 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

• Maintain blood pressure <180/105 mmHg during and after treatment 2
• Do NOT give anticoagulants or antiplatelet agents for 24 hours after tPA administration 2
• Delay aspirin until after the 24-hour post-thrombolysis scan has excluded intracranial hemorrhage 1

Special Populations and Contraindications

Patients on direct oral anticoagulants (DOACs) should NOT receive tPA as routine practice. 1, 4

• Standard coagulation tests (PT/INR, aPTT) do not reliably measure DOAC levels and should not be used to guide tPA decisions 4
• Endovascular therapy may be considered in DOAC patients instead 1, 4
• For patients on antiplatelet therapy prior to stroke, use the same 0.9 mg/kg dose, though there is a 3% absolute increased risk of symptomatic ICH 2

Evidence Supporting Standard Dosing

Lower doses of tPA (<0.9 mg/kg) result in worse functional outcomes without reducing hemorrhage risk. 5

• Patients receiving 0.5-0.7 mg/kg had significantly less excellent recovery (modified Rankin Scale 0-1: 41.89% vs 53.83%) compared to standard dosing 5
• Patients receiving 0.7-0.85 mg/kg had less functional independence (modified Rankin Scale 0-2: 54.33% vs 64.51%) compared to standard dosing 5
• The 90 mg maximum dose is supported by data showing patients >100 kg had higher rates of symptomatic ICH (2.6% vs 1.7%) despite receiving lower per-kg doses 3

Expected Complications

Symptomatic intracranial hemorrhage occurs in 6.4% of tPA-treated patients versus 0.6% of placebo patients. 2

• The baseline symptomatic ICH rate with proper dosing is 4-6% 2
• This risk increases substantially with dosing errors or in anticoagulated patients 2
• Fatal ICH occurs in approximately 3% of treated patients 6

Common Pitfalls to Avoid

• Never exceed 90 mg total dose, even in patients >100 kg—higher doses increase hemorrhage risk without improving outcomes 3
• Never treat beyond 4.5 hours—the ATLANTIS trial showed no benefit and increased harm (symptomatic ICH 7.0% vs 1.1%, fatal ICH 3.0% vs 0.3%) 6
• Never give tPA to patients on DOACs without validated anticoagulant level testing—the bleeding risk is substantially elevated 1, 4
• Never administer antiplatelet or anticoagulant therapy within 24 hours of tPA—wait for the 24-hour post-treatment scan 1, 2

Alternative: Tenecteplase

Tenecteplase 0.25 mg/kg (maximum 25 mg) as a single IV bolus may be considered as an alternative to alteplase in patients with minor neurological impairment and no major intracranial occlusion. 7

• The single-bolus administration offers significant workflow advantages, particularly when considering endovascular therapy or patient transfer 7
• Both agents share similar contraindications 7