tPA Protocol Guideline

tPA Protocol Guide & Dose Calculator

For Acute Ischemic Stroke

Reviewed by the DosePilot Medical Team · Last medically reviewed: June 2026

1
Pre-Administration Checklist

✅ Inclusion Criteria

  • Diagnosis of acute ischemic stroke
  • Symptom onset < 4.5 hours
  • Age ≥ 18 years
  • Baseline NIHSS score assessed

❌ Key Absolute Contraindications

  • Intracranial hemorrhage on CT
  • Active internal bleeding
  • Refractory BP > 185/110 mmHg
  • Use of DOACs within 48 hrs or Warfarin with INR > 1.7
  • Platelet count < 100,000/μL

*This is not an exhaustive list. Review full contraindications in the reference section below.

2
Dose Calculation & Administration

Alteplase dosing is shown below. Tenecteplase 0.25 mg/kg (max 25 mg) as a single IV bolus is a Class 1 alternative (2026 AHA/ASA) — not 0.4 mg/kg, and not the weight-banded STEMI dose.

—

Total Dose (0.9 mg/kg)

— mg

Maximum 90 mg

💉 BOLUS (10%)

— mL

(— mg over 1 min)

💧 INFUSION (90%)

— mL/hr

(— mg over 60 min)

Waste from 100mg vial: — mg
3
Post-Administration Monitoring
  • BP & Neuro Checks: q15 min for 2 hrs, then q30 min for 6 hrs, then q1 hr for the next 16 hrs.
  • BP Target: Maintain blood pressure at or below 180/105 mmHg for 24 hours. Do not lower systolic BP below 140 mmHg — intensive lowering has not improved outcomes after thrombolysis and may cause harm (2026 AHA/ASA).
  • Antithrombotics: HOLD all aspirin, clopidogrel, and anticoagulants for at least 24 hours.
  • Follow-up Imaging: Obtain a follow-up head CT or MRI at 24 hours post-tPA to rule out hemorrhage.

Recent Updates

  • Revised to reflect the 2026 AHA/ASA acute ischemic stroke guideline (replaces the 2019 update).
  • Tenecteplase 0.25 mg/kg (max 25 mg) as a single IV bolus is now a Class 1 alternative to alteplase within 4.5 hours; the 0.4 mg/kg dose is not recommended.
  • Eligibility clarified (treat disabling deficits regardless of NIHSS; non-disabling deficits → antiplatelet therapy preferred) and post-thrombolysis systolic BP should not be lowered below 140 mmHg.

Prabhakaran S, Gonzalez NR, Zachrison KS, et al. 2026 Guideline for the Early Management of Patients With Acute Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association. Stroke. Published online January 26, 2026. PMID 41582814

Key Knowledge Points

  • The standard dose for alteplase (tPA) in acute ischemic stroke is 0.9 mg/kg, with a maximum total dose of 90 mg.
  • Administration is a two-step process: 10% of the total dose as an IV bolus over 1 minute, followed by the remaining 90% as a continuous infusion over 60 minutes.
  • Strict blood pressure control is critical before, during, and after infusion. The target is to maintain BP <185/110 mmHg before treatment and <180/105 mmHg for 24 hours after.
  • Using an accurate tPA dose calculator is essential to prevent medication errors, as incorrect dosing can significantly increase the risk of intracranial hemorrhage.
  • After tPA administration, all antithrombotic (aspirin, clopidogrel) and anticoagulant (heparin, DOACs) therapies must be held for at least 24 hours.

About This tPA Protocol Guide

This tPA protocol guide is an essential tool for healthcare professionals managing acute ischemic stroke. It provides rapid and accurate dosing calculations and integrates them into a step-by-step clinical workflow, from pre-administration checks to post-infusion monitoring. This design helps minimize medication errors during a time-critical intervention and reinforces safety checks. Following a structured tPA protocol guide and using a validated tPA dose calculator is a key step in safely administering thrombolytic therapy.

The Dosing Formula Explained

The calculation for alteplase in acute ischemic stroke is a standardized, weight-based protocol designed to be both effective and safe.

$$ \text{Total Dose (mg)} = \text{Weight (kg)} \times 0.9 \text{ mg/kg} $$

There is a critical safety cap on the total dose:

  • If the calculated dose is greater than 90 mg, the total dose is capped at 90 mg.

The total dose is then divided for administration:

  • Bolus Dose: 10% of the Total Dose (administered over 1 minute).
  • Infusion Dose: 90% of the Total Dose (infused over 60 minutes).

Tenecteplase (TNK): a Class 1 Alternative

The 2026 AHA/ASA guideline recommends either tenecteplase 0.25 mg/kg (maximum 25 mg) as a single IV bolus, or alteplase 0.9 mg/kg, to improve functional outcomes for eligible patients within 4.5 hours (Class 1, Level of Evidence A). Tenecteplase is given as a single bolus with no 1-hour infusion, which can shorten door-to-needle time and simplify interfacility transfer; non-inferiority is supported by the AcT, TRACE-2, and ATTEST-2 trials.

Dose caution: use 0.25 mg/kg for acute ischemic stroke. Tenecteplase 0.4 mg/kg is specifically not recommended, and the stroke dose must not be confused with the higher, weight-banded tenecteplase dose used for STEMI. Eligibility, contraindications, and blood-pressure targets are the same as for alteplase. The calculator on this page computes the alteplase dose; for tenecteplase, give 0.25 mg/kg capped at 25 mg.

Contraindications for Alteplase

The decision to administer tPA requires a careful review of inclusion and exclusion criteria. This tPA protocol guide highlights some of the major contraindications.

Absolute Contraindications

  • Evidence of intracranial hemorrhage on pre-treatment head CT.
  • Significant head trauma or prior stroke in the previous 3 months.
  • Symptoms suggestive of subarachnoid hemorrhage.
  • History of previous intracranial hemorrhage.
  • Active internal bleeding.
  • Known intracranial neoplasm, arteriovenous malformation, or aneurysm.
  • Use of direct oral anticoagulants (DOACs) within 48 hours, or use of warfarin with an INR > 1.7.

Relative Contraindications

These factors increase risk and require careful consideration of the risk-benefit ratio:

  • Only minor or rapidly improving stroke symptoms.
  • Pregnancy.
  • Seizure at onset of stroke.
  • Major surgery or serious trauma within the preceding 14 days.
  • Recent gastrointestinal or urinary tract hemorrhage (within 21 days).

Clinical Interpretation & Limitations

The values provided by this tPA dose calculator are intended to be programmed into an infusion pump, assuming a standard reconstituted concentration of 1 mg/mL.

  • This tool is for informational purposes and is not a substitute for clinical judgment.
  • It does not assess patient eligibility or a full list of contraindications for thrombolysis.
  • The accuracy of this tPA dose calculator depends on an accurate patient actual body weight.
  • All calculations for high-alert medications should be independently verified before administration, in accordance with institutional policy.

Frequently Asked Questions (FAQ)

1. What is the time window for administering tPA?

This is a critical first step in any tPA protocol guide. For most patients, alteplase should be administered within 3 hours of the time the patient was last known to be well. In a select group of patients, this window may be extended to 4.5 hours.

2. What role does the NIHSS score play in this tPA protocol guide?

The NIH Stroke Scale (NIHSS) is a critical tool for quantifying the neurologic deficit. While there is no absolute NIHSS cutoff for giving tPA, it is used to assess stroke severity. The key question is whether the deficit is disabling: a disabling deficit should be treated regardless of a low NIHSS (a small score can still be disabling, e.g., isolated aphasia or hand weakness), whereas a clearly non-disabling deficit (e.g., isolated mild sensory symptoms) is better managed with dual antiplatelet therapy than with thrombolysis. For very severe stroke (NIHSS > 25), efficacy is less certain specifically in the 3–4.5 hour window; this is not an exclusion within 3 hours.

3. What are the specific rules for tPA if a patient is on an anticoagulant?

This is a critical exclusion criterion. tPA is generally contraindicated if a patient has taken a Direct Oral Anticoagulant (DOAC, e.g., apixaban, rivaroxaban) within the last 48 hours, a therapeutic dose of LMWH within the last 24 hours, or is on Warfarin with an INR > 1.7.

4. Why is there a 90 mg maximum dose?

The landmark NINDS trial, which established the efficacy of tPA, used a maximum dose of 90 mg. Clinical data has shown that doses above this limit in patients weighing over 100 kg are associated with a significantly increased risk of intracranial hemorrhage without providing additional therapeutic benefit.

5. Can this tPA protocol guide be used for other conditions like PE or MI?

No. This tPA protocol guide is specifically for the acute ischemic stroke protocol. Dosing for pulmonary embolism (PE) or myocardial infarction (MI) is different and requires a separate protocol and calculator.

Related Calculators

📖 Sources:

  1. Prabhakaran, S., Gonzalez, N. R., Zachrison, K. S., et al. (2026). 2026 Guideline for the Early Management of Patients With Acute Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association. Stroke. Published online January 26, 2026.
  2. Powers, W. J., et al. (2019). Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update (superseded by the 2026 guideline). Stroke, 50(12), e344-e418.
  3. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. (1995). Tissue plasminogen activator for acute ischemic stroke. New England Journal of Medicine, 333(24), 1581-1587.
  4. Menon, B. K., et al. (2022). Intravenous tenecteplase compared with alteplase for acute ischaemic stroke in Canada (AcT). Lancet, 400(10347), 161-169.
  5. Wang, Y., et al. (2023). Tenecteplase versus alteplase in acute ischaemic cerebrovascular events (TRACE-2). Lancet, 401(10377), 645-654.
  6. Muir, K. W., et al. (2024). Tenecteplase versus alteplase for acute stroke within 4.5 h of onset (ATTEST-2). Lancet Neurology, 23(11), 1087-1096.
  7. Alteplase [Prescribing Information]. Genentech, Inc. South San Francisco, CA.

⚠️ Disclaimer:

This tool is for informational and educational purposes only and is not a substitute for professional clinical judgment. All treatment decisions must be made by a qualified healthcare professional considering the individual patient’s full clinical context. This tPA protocol guide is an aid, not a replacement for clinical expertise.

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