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Alteplase (tissue plasminogen activator) is a thrombolytic agent administered intravenously to dissolve blood clots in acute ischaemic stroke. Dosing is strictly weight-dependent: 0.9 mg/kg, with a maximum ceiling of 90 mg. Accurate calculation within the first hours of symptom onset is critical for treatment efficacy and safety. This calculator determines the precise IV dose based on patient weight.

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Creators Małgorzata Koperska, MD
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Understanding Alteplase and Its Mechanism

Alteplase is a recombinant form of tissue plasminogen activator (tPA), a naturally occurring enzyme that breaks down fibrin—the protein scaffold of blood clots. When administered intravenously during acute stroke, alteplase converts plasminogen into plasmin, triggering rapid clot dissolution (fibrinolysis) and restoring blood flow to the brain.

The critical window for thrombolytic therapy is narrow: ideally within 3–4.5 hours of symptom onset for intravenous dosing. Time-sensitive administration and precise dosing are essential to maximise clinical benefit while minimising haemorrhagic complications. In emergency reversal of alteplase toxicity, aminocaproic acid serves as the antidote by inhibiting fibrinolysis.

Weight-Based Alteplase Dosing Formula

Standard intravenous alteplase dosing for acute stroke follows a weight-based protocol. The calculation is straightforward but must be applied consistently across all patients to ensure safety and efficacy.

Alteplase Dose (mg) = 0.9 × Patient Weight (kg)

Maximum Total Dose = 90 mg

  • Patient Weight — Body weight in kilograms (kg)
  • Dose Multiplier — Standard IV dosing coefficient of 0.9 mg/kg for acute ischaemic stroke
  • Maximum Dose Cap — Upper limit of 90 mg regardless of patient weight

Routes of Administration and Clinical Context

Although alteplase can be delivered via multiple routes—intravenous (IV), intra-arterial, intracatheter, intra-hemodialysis catheter, and intrapleural—intravenous administration remains the standard of care in acute stroke. IV dosing offers the fastest onset and widest therapeutic window.

For intravenous thrombolysis, the protocol typically involves:

  • A bolus dose administered over 1 minute
  • The remaining dose infused over 60 minutes
  • Continuous cardiac monitoring and frequent neurological assessment

Intra-arterial and mechanical thrombectomy are reserved for patients outside the IV window or those with large-vessel occlusions, and require different dosing strategies determined by interventional neuroradiology.

Critical Considerations in Alteplase Administration

Several factors can influence safety and efficacy when using alteplase for acute stroke.

  1. Time-Window Constraints — Alteplase must be administered within a narrow therapeutic window (3–4.5 hours from symptom onset for IV, up to 24 hours for selected thrombectomy candidates). Delays in calculation or preparation directly reduce clinical effectiveness. Always confirm the exact time of symptom onset before dosing.
  2. Contraindications and Bleeding Risk — Active bleeding, recent surgery, severe hypertension (>185/110 mmHg), and low platelet counts are major contraindications. Minor head trauma, anticoagulant use, and recent myocardial infarction require careful individualised assessment. Thrombolysis carries inherent intracranial haemorrhage risk (3–6% in clinical trials).
  3. Weight Estimation Accuracy — In emergency settings, patient weight may be estimated rather than measured. Overestimation leads to overdosing; underestimation reduces efficacy. Obtain actual weight whenever possible; use family estimates or medical records rather than guesswork. Even 10 kg errors significantly alter dosing in lighter patients.
  4. Dose Capping at 90 mg — The 90 mg ceiling applies universally, meaning patients weighing >100 kg receive a proportionally lower dose per kilogram. This cap was established in pivotal stroke trials and must not be exceeded, regardless of clinical pressure to increase dosing.

Post-Administration Monitoring and Reversal

After alteplase bolus, observe patients closely for signs of bleeding, neurological deterioration, or allergic reaction. Blood pressure monitoring every 15 minutes for the first 2 hours, then every 30 minutes thereafter, is essential. Any spontaneous bleeding warrants immediate cessation of infusion and consideration of reversal agents.

If serious bleeding occurs, aminocaproic acid (5 g IV load, then 1 g/hour) can be administered to halt fibrinolysis. Fresh frozen plasma and cryoprecipitate may also be needed to replenish depleted clotting factors. Tranexamic acid is an alternative fibrinolysis inhibitor used in some centres.

Frequently Asked Questions

How is the 0.9 mg/kg dose for alteplase determined?

The 0.9 mg/kg dosing regimen comes from the NINDS rt-PA Stroke Study (1995), the landmark trial establishing IV thrombolysis for acute ischaemic stroke. In that trial, patients randomised to 0.9 mg/kg alteplase showed superior 3-month outcomes compared to placebo. The bolus-infusion split (10% over 1 minute, 90% over 60 minutes) was designed to achieve rapid clot disruption while minimising early haemorrhagic transformation.

What happens if a patient weighs more than 100 kg?

Patients weighing >100 kg still receive a maximum total dose of 90 mg (not exceeding 0.9 mg/kg). For example, a 120 kg patient would receive 90 mg, equating to 0.75 mg/kg rather than the standard 0.9 mg/kg. This cap was set in clinical trials to manage systemic fibrinolysis intensity and bleeding risk, and must be strictly respected regardless of clinical circumstances.

Can alteplase be used in patients with prior stroke or diabetes?

Prior ischaemic stroke and diabetes are not absolute contraindications but require careful consideration. Prior stroke increases intracranial haemorrhage risk and may limit benefit if large areas are already infarcted. Diabetic patients tolerate alteplase but may have higher bleeding complications if they also have diabetic vasculopathy. Individual patient assessment by a stroke neurologist is essential; these factors do not preclude treatment but demand heightened monitoring vigilance.

What is the difference between tPA, alteplase, and rtPA?

These terms are often used interchangeably but reflect different naming conventions: tPA (tissue plasminogen activator) is the natural enzyme; rtPA (recombinant tPA) is the laboratory-synthesised version; alteplase is the pharmaceutical name of the rtPA product used clinically. In clinical practice, alteplase and rtPA refer to the same medicine—the recombinant form used for stroke, myocardial infarction, and pulmonary embolism.

How quickly does alteplase work after administration?

Alteplase begins dissolving clots within minutes of IV administration, though peak thrombolytic activity occurs around 5–10 minutes. Clinical improvement (reperfusion) may be evident within 30–60 minutes in patients with rapid, complete clot lysis. However, some patients show delayed or partial response. The full neurological benefit may not be apparent until 24 hours post-infusion, as brain oedema resolves and penumbral tissue recovers.

What should I do if I suspect a dosing error?

Immediately notify the senior clinician and pharmacy. Do not proceed with infusion if the dose is clearly outside the 0.9 mg/kg range (or >90 mg total). If the error is detected post-bolus but before the remainder infuses, the infusion rate can be adjusted or stopped based on clinical judgement. Document the error, the action taken, and the patient's response. Most minor deviations (±10%) have minimal clinical consequence, but significant overdosing carries genuine haemorrhage risk.

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