What is the recommended dosage of Alteplase (tissue plasminogen activator) for thrombolysis in a patient with acute ischemic stroke?

Alteplase Dosing for Acute Ischemic Stroke Thrombolysis

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

Standard Dosing Protocol

The dose calculation is straightforward:

• Total dose = 0.9 mg/kg body weight, with an absolute maximum of 90 mg 1, 2, 3
• Initial bolus = 10% of total dose (0.09 mg/kg) administered IV push over exactly 1 minute 2, 3
• Continuous infusion = 90% of total dose (0.81 mg/kg) administered over 60 minutes 2, 3

This dosing regimen applies to patients treated within 4.5 hours of symptom onset or last known well. 1

Critical Timing Considerations

Initiate alteplase immediately after CT scan confirms absence of hemorrhage, targeting door-to-needle time <60 minutes in 90% of patients, with an optimal median of 30 minutes. 2

• Only blood glucose assessment must precede alteplase administration—do not delay for other laboratory results 1, 3
• Blood pressure must be lowered below 185/110 mmHg before initiating thrombolysis 1, 3
• Do NOT wait to evaluate response to IV thrombolysis before proceeding with mechanical thrombectomy if indicated 1, 3

Maximum Dose Limit Rationale

The 90 mg maximum dose cap is evidence-based and should be strictly observed. 4

• Patients weighing >100 kg receive a lower per-kilogram dose (approximately 0.82 mg/kg vs 0.90 mg/kg) but have similar rates of major neurological improvement and functional independence 4
• Importantly, patients >100 kg who received the capped dose actually had higher rates of symptomatic intracranial hemorrhage (2.6% vs 1.7%) and mortality despite the lower per-kilogram dose, supporting the current upper limit 4

Low-Dose Alteplase: Not Recommended

Do not use the 0.6 mg/kg low-dose regimen as standard therapy—it failed to demonstrate noninferiority to standard dosing for the primary outcome of death or disability. 5

• The ENCHANTED trial (2016) involving 3,310 patients showed that low-dose alteplase (0.6 mg/kg) did not meet noninferiority criteria compared to standard dose (0.9 mg/kg) for death or disability at 90 days 5
• While low-dose had fewer symptomatic intracranial hemorrhages (1.0% vs 2.1%), this safety benefit did not translate to improved functional outcomes 5
• The only potential exception is for patients on direct oral anticoagulants (DOACs) in specialized centers, where Japanese protocols using 0.6 mg/kg have shown comparable safety 6

Common Dosing Errors to Avoid

Never use the myocardial infarction dosing protocol for stroke—this is a critical and potentially harmful error. 2

• The MI protocol uses different dosing (typically 100 mg total with accelerated infusion) and is inappropriate for stroke 2
• Always verify you are using the stroke-specific protocol: 0.9 mg/kg (max 90 mg), 10% bolus over 1 minute, 90% infusion over 60 minutes 1, 2, 3

Extended Window Dosing (3-4.5 Hours)

The same 0.9 mg/kg dosing applies in the 3-4.5 hour window, but with additional exclusion criteria. 1, 7

• Exclude patients >80 years old, those on oral anticoagulants regardless of INR, NIHSS >25, or history of both stroke and diabetes 3
• The ECASS III trial (2008) established efficacy of standard-dose alteplase in this extended window (52.4% favorable outcome vs 45.2% placebo) 7

Special Population Considerations

For patients on DOACs, do not routinely administer alteplase except in comprehensive stroke centers with DOAC level testing and reversal agents available. 2

• Standard 0.9 mg/kg dosing carries uncertain safety in DOAC patients 1
• If treating DOAC patients, the 0.6 mg/kg dose showed comparable safety to non-anticoagulated patients in a Japanese registry (2.5% vs 2.4% symptomatic ICH) 6