What is the recommended loading dose of alteplase (tissue plasminogen activator) for eligible patients presenting with ischemic stroke within 4.5 hours of symptom onset?

Loading Dose of 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, followed by the remaining 90% infused over 60 minutes. 1

Dosing Algorithm

Standard Dosing for All Eligible Patients

• Total dose: 0.9 mg/kg body weight 1
• Maximum dose cap: 90 mg regardless of body weight 1
• Initial bolus: 10% of calculated dose administered IV push over 1 minute 1
• Continuous infusion: Remaining 90% infused over 60 minutes 1

Time Window Application

• 0-3 hours: This dosing regimen applies with Class I, Level A evidence 1
• 3-4.5 hours: Identical dosing regimen with Class I, Level B-R evidence 1, 2
• 4.5-9 hours: Same dosing if CT/MRI perfusion shows core/perfusion mismatch and mechanical thrombectomy is not planned 3
• 4.5-24 hours: Same dosing for patients with salvageable brain tissue on perfusion imaging, though this represents emerging evidence 4

Critical Pre-Treatment Requirements

Blood Pressure Control

• BP must be lowered to <185/110 mmHg before initiating alteplase 1
• BP must remain <180/105 mmHg for at least 24 hours after treatment 1

Laboratory Parameters

• Blood glucose must be >50 mg/dL 1
• Correct glucose if <60 mg/dL or >400 mg/dL before treatment 3

Imaging Requirements

• Non-contrast CT or MRI must exclude intracranial hemorrhage 1
• Early ischemic changes should not exceed 1/3 of MCA territory 1

Special Population Considerations

Patients >100 kg Body Weight

• The 90 mg maximum dose cap applies regardless of weight 5
• Patients >100 kg receive a lower per-kilogram dose (approximately 0.82 mg/kg vs. 0.90 mg/kg) 5
• This lower dose maintains similar efficacy for major neurological improvement and functional independence 5
• However, patients >100 kg have higher rates of symptomatic intracranial hemorrhage (2.6% vs. 1.7%) and mortality despite the lower per-kilogram dose 5

Age Considerations

• No dose adjustment for age 1
• Patients ≥80 years receive the same dosing within the 0-3 hour window 1
• For the 3-4.5 hour window, patients ≤80 years are preferred, but age alone does not change the dose 1

Stroke Severity

• No dose adjustment based on NIHSS score 1
• Severe strokes (high NIHSS) receive the same dosing, though they carry increased hemorrhagic transformation risk 1

Common Pitfalls to Avoid

Dosing Errors

• Never exceed 90 mg total dose, even for patients weighing >100 kg 1, 5
• Never split the bolus and infusion differently than the 10%/90% ratio 1
• Calculate the dose based on actual body weight, not ideal body weight 5

Timing Errors

• Initiate treatment as quickly as possible within the eligible time window—every minute counts 1
• Target door-to-needle time <60 minutes in 90% of patients, with median goal of 30 minutes 6, 7

Contraindication Misunderstandings

• Prior antiplatelet monotherapy (aspirin or clopidogrel) is not a contraindication to standard dosing 1
• Prior dual antiplatelet therapy increases symptomatic ICH risk but does not change the dose 1
• End-stage renal disease on hemodialysis is not a contraindication to standard dosing 1

Post-Administration Management

Antithrombotic Therapy Timing

• Avoid antithrombotic therapy for 24 hours after alteplase administration 1
• Early initiation (<24 hours) may be considered only when withholding poses substantial risk from concomitant conditions 1

Hemorrhage Risk

• Symptomatic intracranial hemorrhage occurs in 2.4% of patients treated in the 3-4.5 hour window 2
• Risk increases to 3.8% in extended window (4.5-24 hours) with perfusion selection 4
• Any intracranial hemorrhage (symptomatic or asymptomatic) occurs in approximately 27% of treated patients 2