What is the administration protocol for alteplase (tissue plasminogen activator) in patients with ischemic stroke?

Alteplase Administration Protocol for Ischemic Stroke

Alteplase should be administered at a dose of 0.9 mg/kg (maximum 90 mg), with 10% given as an intravenous bolus over one minute and the remaining 90% as an intravenous infusion over 60 minutes, as soon as possible after hospital arrival and CT scan confirmation of ischemic stroke. 1

Timing of Administration

• Treatment should be initiated as soon as possible after patient arrival and CT scan, with a target door-to-needle time of less than 60 minutes in 90% of treated patients, and a median door-to-needle time of 30 minutes 1
• Eligible patients can receive alteplase within 3 hours of stroke symptom onset or last known well time regardless of age or stroke severity 1
• Selected patients can receive alteplase between 3-4.5 hours of stroke onset with the following considerations:
  • Age ≤80 years
  • No history of both diabetes mellitus and prior stroke
  • NIHSS score ≤25
  • Not taking oral anticoagulants
  • No imaging evidence of ischemic injury involving more than one-third of the MCA territory 1
• Recent evidence suggests potential benefit for selected patients with salvageable brain tissue identified by perfusion imaging between 4.5-24 hours after onset, though this is not yet in standard guidelines 2

Dosing Protocol

• Calculate dose based on 0.9 mg/kg body weight (maximum 90 mg total) 1
• Administer 10% (0.09 mg/kg) as an intravenous bolus over one minute 1
• Administer remaining 90% (0.81 mg/kg) as an intravenous infusion over 60 minutes 1
• CAUTION: The dosing protocol for alteplase in stroke is different from the protocol for myocardial infarction 1

Pre-Administration Requirements

• Confirm eligibility through clinical assessment and CT scan to rule out intracranial hemorrhage 1
• Check blood pressure - must be <185/110 mmHg before initiating alteplase 1
• Check blood glucose (must be >50 mg/dL or >3.3 mmol/L) 1
• When uncertain about treatment eligibility, urgently consult with a stroke specialist within the institution or through telestroke services 1
• If uncertain about CT imaging interpretation, consult a radiologist 1

Contraindications

• Intracranial hemorrhage on CT scan 1
• Extensive regions of clear hypoattenuation on CT scan 1
• Stroke or serious head trauma within the past 3 months 1
• Major surgery within past 14 days 1
• Gastrointestinal or urinary bleeding within past 21 days 1
• Patients on direct oral anticoagulants (DOACs) should not routinely receive alteplase unless specialized testing of DOAC levels and reversal agents are available 1
• Platelet count <100,000/mm³ 1
• International normalized ratio (INR) >1.7 in patients on oral anticoagulants 1

Management of Complications

• For angioedema: implement a staged response using antihistamines, glucocorticoids, and standard airway management as per local protocol 1
• For alteplase-associated bleeding: individual case-by-case decisions regarding use of cryoprecipitate, fresh frozen plasma, prothrombin complex concentrates, tranexamic acid, factor VIIa, or platelet transfusions 1
• Monitor for symptomatic intracranial hemorrhage, which occurs in approximately 2.4% of patients treated between 3-4.5 hours 3

Special Considerations

• Endovascular thrombectomy (EVT) should be considered for eligible patients with large vessel occlusion, and alteplase should not delay EVT when indicated 1
• Patients eligible for both alteplase and EVT should receive alteplase while simultaneously preparing for EVT 1
• Hospital inpatients who develop acute stroke symptoms should be rapidly evaluated by a specialist team and provided access to appropriate acute stroke treatments 1
• In pregnant women and pediatric patients with acute ischemic stroke, urgent consultation with a stroke specialist is recommended 1

Pitfalls to Avoid

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