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 calculated dose given as an intravenous bolus over 1 minute, followed by the remaining 90% infused over 60 minutes. 1
Standard Dosing Protocol
- Total dose: 0.9 mg/kg body weight, not to exceed 90 mg maximum 1, 2
- Initial bolus: 10% of total calculated dose administered intravenously over 1 minute 1, 3
- Continuous infusion: Remaining 90% infused over 60 minutes 1, 3
For example, a 70 kg patient would receive:
- Total dose: 63 mg (70 kg × 0.9 mg/kg)
- Bolus: 6.3 mg over 1 minute
- Infusion: 56.7 mg over 60 minutes
Time Window for Administration
The strength of recommendation varies significantly based on time from symptom onset:
- 0-3 hours: Strong recommendation (Grade 1A) - This is the FDA-approved window with the strongest evidence for benefit 1, 4
- 3-4.5 hours: Conditional recommendation (Grade 2C) - Treatment is reasonable but requires more careful patient selection 1, 4
- Beyond 4.5 hours: Strong recommendation AGAINST treatment (Grade 1B) - Do not administer tPA beyond this window 1, 4
The ECASS III trial extended the treatment window to 4.5 hours, but used more restrictive patient selection criteria than current U.S. practice for the 0-3 hour window. 5
Evidence Supporting Standard Dose
Do not use lower doses of tPA. A large Chinese registry study (TIMS-China) with 919 patients demonstrated that the standard 0.85-0.95 mg/kg dose resulted in significantly better functional outcomes compared to lower doses:
- Patients receiving 0.5-0.7 mg/kg had 41.89% excellent recovery (mRS 0-1) versus 53.83% with standard dose (OR 0.58, p=0.031) 6
- Patients receiving 0.7-0.85 mg/kg had 54.33% functional independence (mRS 0-2) versus 64.51% with standard dose (OR 0.66, p=0.036) 6
- No significant difference in symptomatic intracranial hemorrhage or mortality between dose groups 6
This finding is particularly important because some Asian populations were previously thought to potentially benefit from lower doses, but the evidence clearly supports 0.9 mg/kg as optimal. 6, 7
Critical Safety Considerations
Symptomatic intracranial hemorrhage (sICH) rates:
- Baseline rate with proper dosing: 4-6% 1
- NINDS trial: 6.4% with tPA versus 0.6% with placebo 1
- Real-world practice: 7% in early clinical implementation 2
Patients on antiplatelet therapy prior to stroke have a 3% absolute increased risk of symptomatic ICH but should still receive tPA if otherwise eligible. 1
Patients on direct oral anticoagulants (DOACs) should NOT receive tPA as routine practice due to substantially elevated bleeding risk. 8, 1
Pre-Treatment Requirements
Before administering the loading dose:
- Blood pressure must be controllable to <185/110 mmHg 3
- Insert all necessary IV lines, Foley catheter, and indwelling tubes BEFORE tPA administration to minimize trauma and bleeding risk 3
- Complete dysphagia screening before any oral medications 8
- Exclude intracranial hemorrhage on non-contrast head CT 3
Post-Loading Dose Management
Monitoring intensity after bolus administration:
- Every 15 minutes during the 60-minute infusion 3
- Every 15 minutes for 2 hours after infusion completion 3
- Every 30 minutes for the next 6 hours 3
- Hourly for 16 hours thereafter 3
Obtain urgent head CT if patient develops:
Delay aspirin until 24 hours after tPA administration and after repeat imaging excludes intracranial hemorrhage. 8, 1
Common Pitfalls to Avoid
Do not exceed 90 mg total dose even in patients weighing >100 kg, as higher doses increase hemorrhage risk without improving outcomes. 1
Do not use lower doses in Asian patients - the evidence clearly demonstrates that 0.9 mg/kg is superior to lower doses even in Chinese populations. 6, 7
Do not delay tPA administration to obtain vascular imaging if the patient meets clinical criteria for thrombolysis within the time window. 3
Do not give tPA if blood pressure cannot be reduced below 185/110 mmHg despite antihypertensive therapy. 3