What is the recommended dose and administration of intravenous (IV) alteplase (tissue plasminogen activator) for thrombolysis?

Recommended Dosing and Administration of IV Alteplase for Thrombolysis

For adult patients with acute ischemic stroke, IV alteplase should be administered at a dose of 0.9 mg/kg (maximum 90 mg total), with 10% given as an intravenous bolus over one minute and the remaining 90% as an intravenous infusion over 60 minutes. 1, 2

Standard Dosing Protocol

• Calculate dose based on patient's body weight: 0.9 mg/kg (maximum dose 90 mg) 1, 2
• Administer 10% of total dose (0.09 mg/kg) as an IV bolus over 1 minute 1, 2
• Administer remaining 90% of dose (0.81 mg/kg) as an IV infusion over 60 minutes 1, 2
• Treatment should be initiated as soon as possible after hospital arrival and CT scan confirmation of ischemic stroke 1

Timing of Administration

• Alteplase should be administered within 4.5 hours of stroke symptom onset or last known well time 1, 2
• Target door-to-needle time should be less than 60 minutes in 90% of treated patients, with a median door-to-needle time of 30 minutes 1, 2
• For patients with unclear time of onset >4.5 hours from last known well (including wake-up strokes), alteplase can be administered within 4.5 hours of symptom recognition if MRI shows DWI-FLAIR mismatch 1
• For patients with symptom onset between 4.5-9 hours who have CT or MRI core/perfusion mismatch, consider alteplase if mechanical thrombectomy is not indicated or planned 1

Pre-Administration Requirements

• Blood glucose must be checked before initiating alteplase (only essential lab test required before administration) 1, 2
• Blood pressure must be <185/110 mmHg before initiating alteplase 1, 2
• Brain imaging (CT or MRI) must be performed to rule out intracranial hemorrhage 1, 2

Special Considerations

• For patients >100 kg, the maximum dose remains 90 mg, resulting in a lower per-kilogram dose (0.82 mg/kg vs 0.9 mg/kg) 3

  • Despite receiving a lower per-kilogram dose, patients >100 kg showed similar rates of major neurological improvement and functional independence compared to patients ≤100 kg 3
  • However, patients >100 kg had higher rates of symptomatic intracerebral hemorrhage (2.6% vs 1.7%) 3

• For patients taking direct oral anticoagulants (DOACs), alteplase should not routinely be administered 1, 2

  • Mechanical thrombectomy may be considered for these patients if eligible 1
  • Some evidence suggests that low-dose alteplase (0.6 mg/kg) may be safe in patients on DOACs, but this is not standard practice in most guidelines 4

Management During Administration

• Continue to monitor vital signs, particularly blood pressure 1, 2
• Be prepared to manage complications, especially angioedema and bleeding 1, 2
• For angioedema: implement a staged response using antihistamines, glucocorticoids, and standard airway management 1, 2

Common Pitfalls to Avoid

• Delaying treatment - "Time is Brain" - every minute counts in stroke treatment 2
• Using incorrect dosing protocol (confusing with myocardial infarction protocol) 1, 2
• Withholding treatment from eligible elderly patients (>80 years) within the 3-hour window 1, 2
• Waiting for all laboratory results before initiating treatment - only blood glucose must be checked before administration 1, 2
• Evaluating response to alteplase before proceeding with catheter angiography for mechanical thrombectomy when both are indicated 1

Alternative Dosing Considerations

• Low-dose alteplase (0.6 mg/kg) has been studied as an alternative to standard dosing 5, 6
• The ENCHANTED trial showed that low-dose alteplase was associated with significantly fewer symptomatic intracerebral hemorrhages (1.0% vs 2.1%) 5
• However, low-dose alteplase did not meet the noninferiority margin for the primary outcome of death and disability at 90 days 5
• Therefore, standard-dose alteplase (0.9 mg/kg) remains the recommended dosing regimen for most patients 1, 2