How to administer alteplase (tissue plasminogen activator)?

How to Administer Alteplase 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 and the remaining 90% as an IV infusion over 60 minutes. 1

Dosing Protocol

The critical dosing distinction: Alteplase dosing for stroke differs completely from myocardial infarction protocols—using the MI protocol in stroke patients is a dangerous error. 1

Weight-Based Calculation

• Total dose: 0.9 mg/kg body weight, maximum 90 mg 1
• Initial bolus (10%): 0.09 mg/kg IV push over exactly 1 minute 1
• Infusion (90%): 0.81 mg/kg IV infusion over 60 minutes 1

Example: For a 75 kg patient:

• Total dose = 67.5 mg
• Bolus = 6.75 mg over 1 minute
• Infusion = 60.75 mg over 60 minutes

Timing Targets

Door-to-needle time is critical for mortality and morbidity reduction:

• Target: <60 minutes in 90% of patients 1
• Optimal median: 30 minutes 1
• Initiate immediately after CT scan confirms no hemorrhage 1
• Every minute of delay worsens outcomes—time is brain 1

Time Windows for Administration

Standard Window (0-4.5 hours)

• 0-3 hours: Standard indication with strongest evidence 2
• 3-4.5 hours: Approved for selected patients who meet ALL criteria: 2, 3
  • Age ≤80 years
  • No history of BOTH diabetes AND prior stroke
  • NIHSS score ≤25
  • Not taking oral anticoagulants
  • No imaging evidence of infarction >1/3 MCA territory

Extended Window (4.5-24 hours)

• Recent breakthrough evidence: The 2025 HOPE trial demonstrated functional benefit when salvageable tissue is identified on perfusion imaging 4
• Requires perfusion imaging (CT or MR perfusion) showing salvageable penumbra 4
• Increased symptomatic ICH risk (3.8% vs 0.51%) but no mortality increase 4
• Consult stroke specialist before administering beyond 4.5 hours 1

Pre-Administration Requirements

Blood Pressure Management

Mandatory: Lower BP to <185/110 mmHg BEFORE starting alteplase 2

• Failure to control BP increases hemorrhagic transformation risk
• Use IV labetalol or nicardipine per institutional protocol

Imaging Confirmation

• Non-contrast CT head: Must exclude intracranial hemorrhage 2
• If uncertain about CT interpretation: Immediately consult radiology 1
• ASPECTS score: Assess for extensive early infarct changes 1
• Consider advanced imaging (CTP/MRP): For patients beyond 6 hours or wake-up strokes 1

Critical Contraindications

Absolute contraindications that prevent administration: 2

• Evidence of intracranial hemorrhage on CT
• Severe head trauma within 3 months
• Ischemic stroke within 3 months
• History of intracranial hemorrhage
• Coagulopathy: platelets <100,000/mm³, INR >1.7, aPTT >40s, or PT >15s
• LMWH within 24 hours
• Active internal bleeding or GI/GU hemorrhage within 21 days

DOAC Considerations

Do NOT routinely administer alteplase to patients on DOACs 1

• Exception: Comprehensive stroke centers with DOAC level testing and reversal agents available—requires hematology consultation 1
• Consider endovascular thrombectomy instead for DOAC patients 1

Post-Administration Management

Antiplatelet Delay

Hold all antiplatelet agents for 24 hours post-alteplase 2

• Obtain 24-hour post-thrombolysis CT to exclude hemorrhage before starting antiplatelets 2

Monitoring for Complications

Angioedema management: 1

• Staged response: antihistamines → glucocorticoids → standard airway management per protocol
• Most common non-hemorrhagic complication

Hemorrhage management: 1

• No routine use of cryoprecipitate, FFP, PCC, tranexamic acid, factor VIIa, or platelets
• Decisions made case-by-case based on severity and location

Special Populations

Uncertain Cases

When eligibility is unclear: Urgently consult stroke specialist via telestroke or in-person 1

Hospital Inpatients

Inpatients developing acute stroke symptoms require same rapid evaluation and treatment access as ED patients 1

Pediatric and Pregnancy

Limited trial data—requires stroke expert consultation and shared decision-making with family 1

Common Pitfalls to Avoid

1. Using MI dosing protocol: The 100 mg accelerated infusion for MI is incorrect and potentially harmful in stroke 1
2. Delaying for "perfect" workup: Every 15-minute delay reduces favorable outcomes—treat based on non-contrast CT alone when within window 1
3. Administering to DOAC patients: High hemorrhage risk without specialized testing 1
4. Starting antiplatelets immediately: Wait 24 hours and obtain repeat imaging 2
5. Inadequate BP control: Uncontrolled hypertension dramatically increases ICH risk 2