What is the recommended loading dose of tissue plasminogen activator (tPA) for ischemic stroke?

Loading Dose of tPA for Acute Ischemic Stroke

The recommended loading dose of tissue plasminogen activator (tPA) for acute ischemic stroke is 0.9 mg/kg (maximum 90 mg total), with 10% of the total calculated dose administered as an intravenous bolus over 1 minute, followed by the remaining 90% infused over 60 minutes. 1

Dosing Protocol

The standard dosing regimen is:

• Total dose: 0.9 mg/kg (not to exceed 90 mg maximum) 1
• Initial bolus: 10% of total dose administered intravenously over 1 minute 1
• Continuous infusion: Remaining 90% infused over 60 minutes 1

This dosing protocol is based on the landmark NINDS tPA Stroke Study, which demonstrated improved functional outcomes at 3 months with a number needed to treat of 8.3 for achieving minimal or no disability. 1

Critical Weight Measurement Requirement

Accurate patient weight measurement is essential before calculating the tPA dose. Estimation errors occur in 22.7% of cases when weight is estimated rather than measured, with healthcare staff estimates being inaccurate 44% of the time. 2 Each 10% increase in tPA dose above the optimal 0.9 mg/kg increases the risk of intracerebral hemorrhage (OR 3.10; 95% CI 1.14-8.39). 2

Best practice:

• Weigh the patient on a calibrated scale before dose calculation 2
• If weighing is impossible, have the patient self-report their weight (only 11% inaccuracy) rather than staff estimation 2
• Never exceed the 90 mg maximum total dose regardless of patient weight 1

Time Window Considerations

The dosing regimen remains 0.9 mg/kg regardless of treatment time window:

• Within 3 hours of symptom onset: Strong recommendation (Grade 1A) 1
• Between 3-4.5 hours of symptom onset: Conditional recommendation (Grade 2C) 1
• Beyond 4.5 hours: tPA is contraindicated (Grade 1B) 1

The absolute benefit is greatest when treatment is initiated earliest, with earlier treatment resulting in greater proportional benefit. 1 Once the decision to administer tPA is made, treat as rapidly as possible within the appropriate time window. 1

Geographic Dosing Variations

Note that Japan uses a lower dose of 0.6 mg/kg, but this is not the standard in North America or Europe. 1 Studies comparing different doses in Chinese patients showed a trend toward better outcomes with 0.9 mg/kg (51.1% favorable outcome) compared to 0.6-0.7 mg/kg (34.8% favorable outcome), though this did not reach statistical significance. 3 The 0.9 mg/kg dose remains the evidence-based standard for most populations. 1

Common Pitfalls to Avoid

Critical errors that increase hemorrhagic risk:

• Overdosing due to weight estimation errors - always measure actual weight 2
• Exceeding the 90 mg maximum dose - even if calculated dose based on weight would be higher 1
• Administering the bolus too rapidly or too slowly - must be given over exactly 1 minute 1
• Incorrect infusion rate for the remaining dose - must be delivered over exactly 60 minutes 1

The baseline symptomatic intracranial hemorrhage rate with proper dosing is 4-6%, which increases substantially with dosing errors or in anticoagulated patients. 4 In the NINDS trial, symptomatic ICH occurred in 6.4% of tPA-treated patients versus 0.6% of placebo patients. 1

Special Populations

Patients on direct oral anticoagulants (DOACs) like apixaban should NOT receive tPA as routine practice due to substantially elevated bleeding risk. 4 In these patients, proceed directly to mechanical thrombectomy evaluation if large vessel occlusion is present. 4

For patients on antiplatelet therapy prior to stroke, the same 0.9 mg/kg dose is used, though there is a 3% absolute increased risk of symptomatic ICH compared to those not on antiplatelet therapy. 1