What are the eligibility criteria for administering tPA (alteplase) to a patient with acute ischemic stroke?

Eligibility for tPA in Acute Ischemic Stroke

Time-Based Eligibility Framework

Administer IV alteplase (0.9 mg/kg, maximum 90 mg) to all patients with acute ischemic stroke who present within 3 hours of symptom onset and meet NINDS criteria, regardless of age, stroke severity, or antiplatelet use. 1, 2

0-3 Hour Window (Strongest Evidence)

• All eligible patients within 3 hours should receive alteplase immediately – this provides a 12% absolute increase in achieving minimal or no disability (39% vs 26% with placebo), with a number needed to treat of 8.3. 1, 2
• Age >80 years is not a contraindication in this window. 1, 2, 3
• Severe stroke (NIHSS >25) is not a contraindication in this window. 1, 2
• Current single or dual antiplatelet therapy (aspirin, clopidogrel, or both) is not a contraindication. 1, 2
• Preexisting disability (mRS ≥2) or dementia may still warrant treatment based on premorbid function and goals of care. 1

3-4.5 Hour Extended Window

• Alteplase should be considered for patients meeting ECASS III criteria between 3-4.5 hours (odds ratio 1.40 for favorable outcome vs placebo). 1, 2
• Additional exclusions apply in this window only: 1, 2, 3
  • Age >80 years
  • Any oral anticoagulant use (regardless of INR)
  • NIHSS >25
  • Combined history of diabetes and prior stroke
  • Imaging showing ischemic injury >1/3 MCA territory

Beyond 4.5 Hours

• Do not administer IV alteplase beyond 4.5 hours from symptom onset (Grade 1B recommendation against use). 1
• Exception: A 2025 trial (HOPE) demonstrated benefit for alteplase administered 4.5-24 hours after onset in patients with salvageable brain tissue on perfusion imaging, though this increased symptomatic ICH from 0.51% to 3.8%. 4

Mandatory Pre-Treatment Requirements

Three absolute requirements before administering alteplase: 2, 3

1. Non-contrast CT or MRI to exclude intracranial hemorrhage 1, 2, 3
2. Blood pressure <185/110 mmHg before initiating treatment (maintain <180/105 mmHg for 24 hours after) 1, 2, 3
3. Blood glucose >50 mg/dL (>2.7 mmol/L) confirmed at bedside 1, 2, 3

• Do not delay treatment waiting for complete laboratory panels – only bedside glucose is mandatory before administration. 2, 3

Absolute Contraindications

Never administer alteplase if any of the following are present: 1, 2, 3

• Intracranial hemorrhage on CT/MRI
• Ischemic stroke or serious head trauma within past 3 months
• History of intracranial hemorrhage
• Intracranial/intraspinal surgery within past 3 months
• Gastrointestinal bleeding within past 21 days
• Major surgery within past 14 days
• Platelets <100,000/mm³
• INR >1.7
• aPTT >40 seconds or PT >15 seconds
• Current use of direct oral anticoagulants (DOACs) without specialized reversal capability 5, 3
• Extensive hypoattenuation on CT (>1/3 MCA territory)

Relative Contraindications Requiring Case-by-Case Assessment

The following situations may allow alteplase use with careful consideration: 1

• Warfarin use with INR ≤1.7 and/or PT <15 seconds (Class IIb) 1
• Seizure at stroke onset if deficits are clearly from stroke, not postictal (Class IIa) 1
• Blood glucose initially <50 or >400 mg/dL that is subsequently normalized (Class IIb) 1
• Lumbar puncture within preceding 7 days (Class IIb) 1
• Major trauma within 14 days not involving the head – weigh bleeding risk against stroke disability (Class IIb) 1
• Major surgery within 14 days – consider surgical-site hemorrhage risk (Class IIb) 1
• Menstruation without menorrhagia history (Class IIa); with menorrhagia but stable hemodynamics (Class IIb) 1
• Extracranial cervical arterial dissection (Class IIa – reasonably safe) 1
• Intracranial arterial dissection (Class IIb – uncertain risk) 1
• Early improvement but remaining moderately impaired (Class IIa) 1

Dosing Protocol

Standard alteplase regimen: 1, 2, 3

• Total dose: 0.9 mg/kg (maximum 90 mg absolute)
• 10% (0.09 mg/kg) as IV bolus over exactly 1 minute
• Remaining 90% (0.81 mg/kg) as continuous infusion over 60 minutes

Integration with Mechanical Thrombectomy

Critical workflow principles: 2, 5, 3

• Administer IV alteplase even when mechanical thrombectomy is planned – these are complementary therapies. 2, 5
• Do not delay IV thrombolysis to obtain or interpret CTA. 2, 3
• Do not wait to assess response to alteplase before proceeding to catheter angiography. 2, 3
• For suspected large vessel occlusion, obtain CTA from aortic arch to vertex immediately after non-contrast CT, but start alteplase without waiting for results. 2

Hemorrhage Risk and Monitoring

• Symptomatic intracranial hemorrhage occurs in 2.4-6.4% of treated patients with standard dosing. 1, 2
• NIHSS >20 is a stronger predictor of symptomatic hemorrhage than age alone. 2
• Hyperglycemia >11.1 mmol/L (>200 mg/dL) increases symptomatic ICH risk to 36%. 2
• Monitor neurological status every 15 minutes during infusion, every 30 minutes for 6 hours, then hourly until 24 hours. 2
• If severe headache, acute hypertension, nausea, or vomiting occur, stop infusion immediately and obtain emergent CT. 2
• Delay antiplatelet therapy for 24 hours after alteplase; obtain follow-up CT at 24 hours before starting antiplatelets or anticoagulants. 2, 5

Common Pitfalls to Avoid

• Withholding alteplase from patients >80 years old within the 0-3 hour window – age is only an exclusion in the 3-4.5 hour window. 2, 3
• Waiting for complete laboratory results beyond bedside glucose – every 15-minute delay reduces favorable outcomes. 1, 2
• Delaying IV thrombolysis while evaluating for thrombectomy – administer alteplase first, evaluate simultaneously. 2, 3
• Excluding patients with mild deficits who are improving – if moderately impaired, alteplase is reasonable. 1
• Using incorrect dosing (confusing with MI protocol of 100 mg) – stroke dose is 0.9 mg/kg maximum 90 mg. 3

Institutional Requirements

Alteplase effectiveness requires organized stroke systems including: 1, 2

• 24/7 rapid CT availability
• Dedicated stroke team
• Continuous neurological monitoring capability
• Blood pressure management protocols
• Neurosurgical consultation availability
• Target door-to-needle time <60 minutes (median 30 minutes) 3