What is the recommended dose and administration of alteplase (tissue plasminogen activator) for thrombolytic therapy in acute ischemic stroke?

Alteplase Dosing for Acute Ischemic Stroke

Administer alteplase at 0.9 mg/kg (maximum 90 mg total) with 10% given as an IV bolus over 1 minute, followed by the remaining 90% as an IV infusion over 60 minutes. 1, 2, 3

Exact Dosing Protocol

• Calculate the total dose: 0.9 mg/kg body weight with an absolute maximum of 90 mg regardless of patient weight 1, 2
• Bolus administration: Give 10% of the total calculated dose (0.09 mg/kg) as IV push over exactly 1 minute 1, 2, 3
• Infusion administration: Give the remaining 90% of the total dose (0.81 mg/kg) as continuous IV infusion over 60 minutes 1, 2, 3

Time Windows for Administration

• 0-3 hours: Alteplase is indicated for all eligible patients regardless of age or stroke severity 1, 3
• 3-4.5 hours: Alteplase is indicated for patients meeting ALL of the following criteria: age ≤80 years, no history of both diabetes AND prior stroke, NIHSS ≤25, not taking oral anticoagulants, and no imaging evidence of ischemic injury involving >1/3 of MCA territory 1, 3
• 4.5-9 hours: Consider alteplase only in patients with CT or MRI core/perfusion mismatch when mechanical thrombectomy is not indicated or planned 1

Pre-Administration Requirements

Only blood glucose must be checked before initiating alteplase - do not delay for other laboratory results 1, 2, 3

• Blood glucose must be >50 mg/dL (>3.3 mmol/L); treat hypoglycemia with IV dextrose before alteplase 1
• Blood pressure must be lowered to <185/110 mmHg before starting alteplase 1, 3
• Non-contrast CT must confirm absence of intracranial hemorrhage 1, 3

Timing Targets

• Door-to-needle time: <60 minutes in 90% of patients, with optimal median of 30 minutes 2, 3
• Initiate alteplase immediately after CT confirms no hemorrhage 2, 3
• Do not delay alteplase to evaluate response before proceeding with mechanical thrombectomy if both are indicated 1, 3

Critical Contraindications

Absolute contraindications that preclude alteplase administration: 1, 2, 3

• Intracranial hemorrhage on CT
• Severe head trauma within 3 months
• Ischemic stroke within 3 months
• History of intracranial hemorrhage
• Platelets <100,000/mm³
• INR >1.7, aPTT >40 seconds, or PT >15 seconds
• Active internal bleeding or GI/urinary bleeding within 21 days
• Major surgery within 14 days
• Patients on direct oral anticoagulants (DOACs) should NOT routinely receive alteplase unless in comprehensive stroke centers with DOAC level testing and reversal agents available 2, 3

Post-Administration Management

• Hold all antiplatelet agents for 24 hours after alteplase administration 2, 3
• Perform 24-hour post-thrombolysis scan to exclude intracranial hemorrhage before initiating any antiplatelet therapy 2
• For angioedema: use staged response with antihistamines, glucocorticoids, and standard airway management 2, 3

Special Population Considerations

Patients >100 kg body weight: The 90 mg maximum dose limit is supported by evidence showing higher rates of symptomatic intracranial hemorrhage (2.6% vs 1.7%) and mortality when patients >100 kg receive the capped dose, despite the lower per-kilogram dosing 4

Patients >80 years old: Within the 0-3 hour window, alteplase is equally recommended regardless of age; between 3-4.5 hours, age >80 is an exclusion criterion per guidelines 1, 3

Patients on DOACs: A Japanese study using 0.6 mg/kg alteplase showed comparable safety in DOAC patients, but this lower dose is NOT the standard in Western guidelines 5. The standard 0.9 mg/kg dose should not be used in DOAC patients outside comprehensive stroke centers 2, 3

Critical Pitfalls to Avoid

• Do NOT use the myocardial infarction dosing protocol (which differs significantly) - this is incorrect and potentially harmful 2, 3
• Do NOT wait for complete laboratory workup - only glucose must precede alteplase administration 1, 2, 3
• Do NOT withhold alteplase from patients >80 years within 3 hours - age is not a contraindication in this window 1, 3
• Do NOT delay alteplase to assess response before proceeding with mechanical thrombectomy when both are indicated 1, 3
• Do NOT use lower doses - a large trial showed 0.6 mg/kg was NOT noninferior to 0.9 mg/kg for the primary outcome of death or disability, despite fewer hemorrhages 6