What are the conditions where recombinant tissue plasminogen activator (rtPA) is indicated for adults with acute ischemic stroke?

Conditions Where rtPA is Indicated

Recombinant tissue plasminogen activator (rtPA) is FDA-approved exclusively for acute ischemic stroke in adults, with administration within 3 hours of symptom onset as the primary indication, and an extended 3-4.5 hour window supported by guidelines for carefully selected patients. 1

Primary Indication: Acute Ischemic Stroke (0-3 Hour Window)

rtPA is indicated for adults with acute ischemic stroke causing measurable neurological deficit who can be treated within 3 hours of symptom onset. 1, 2

Essential Inclusion Criteria:

• Diagnosis of ischemic stroke with measurable neurological deficit that is not clearing spontaneously and not minor/isolated 1
• Age ≥18 years 2, 3
• Symptom onset <3 hours before treatment initiation 1, 2
• CT scan excluding intracranial hemorrhage 2, 3
• Blood pressure controlled to systolic <185 mmHg and diastolic <110 mmHg 1, 2

Absolute Contraindications (Any Time Window):

The following conditions absolutely preclude rtPA administration:

• Any history of intracranial hemorrhage 1, 3
• Head trauma or prior stroke within previous 3 months 1
• Myocardial infarction within previous 3 months 1
• Gastrointestinal or urinary tract hemorrhage within previous 21 days 1
• Major surgery within previous 14 days 1
• Arterial puncture at noncompressible site within previous 7 days 1, 3
• Evidence of active bleeding or acute trauma (fracture) on examination 1, 3
• Platelet count <100,000/mm³ 1, 3
• INR >1.7 or PT >15 seconds if taking oral anticoagulants 1, 4, 3
• Elevated aPTT if heparin received within 48 hours 1
• Blood glucose <50 mg/dL 1, 3
• CT showing multilobar infarction (hypodensity >1/3 cerebral hemisphere) 1, 2
• Symptoms suggestive of subarachnoid hemorrhage 1

Extended Indication: 3-4.5 Hour Window

rtPA may be administered between 3-4.5 hours after symptom onset for carefully selected patients without additional exclusion factors, though this remains off-label in the US. 2, 3

Additional Exclusion Criteria for 3-4.5 Hour Window:

• Age >80 years 2, 3
• Severe stroke with NIHSS >25 2, 3
• Taking any oral anticoagulant regardless of INR 2, 3
• History of BOTH diabetes mellitus AND prior ischemic stroke 2, 3

Special Considerations

Severe Strokes:

Patients with major strokes (NIHSS >22) have very poor prognosis but some positive treatment effect with rtPA has been documented; the decision to treat should be made with caution given considerable hemorrhage risk. 1

Seizures at Onset:

rtPA may be used in patients with seizures at presentation when evidence suggests residual deficits are due to ischemia rather than postictal state. 1

Time-Critical Implementation:

Treatment can be initiated before coagulation studies are available in patients without recent anticoagulant or heparin use, but must be discontinued if INR >1.7 or PT elevated. 4

Earlier treatment within 90 minutes is more likely to result in favorable outcome, with number needed to treat of 8 within the 0-3 hour window. 2

Institutional Requirements

rtPA should only be administered in settings with:

• Clearly defined protocol and knowledgeable stroke team 2, 3
• Institutional commitment to acute stroke care 2, 3
• Rapid access to CT imaging 2
• Immediate laboratory capabilities 2
• Door-to-needle time within 60 minutes of hospital arrival 3

Critical Safety Profile

Symptomatic intracranial hemorrhage occurs in 6.4% of rtPA-treated patients versus 0.6% with placebo, with 13% more patients achieving excellent functional outcomes. 2, 3

Mortality at 3 months is similar between treated and untreated patients (17% vs 20%). 3

Common Pitfall

Treatment beyond 3-5 hours after symptom onset is NOT indicated; the ATLANTIS trial demonstrated no significant benefit and increased symptomatic ICH (7.0% vs 1.1%) and fatal ICH (3.0% vs 0.3%) when rtPA was administered between 3-5 hours. 5