When is thrombolysis with tissue plasminogen activator (tPA) indicated for ischemic stroke?

When to Thrombolyse for Stroke

Administer IV tPA (0.9 mg/kg, maximum 90 mg) for acute ischemic stroke within 3 hours of clearly defined symptom onset as a strong recommendation, with conditional support for treatment between 3-4.5 hours, and do not treat beyond 4.5 hours. 1, 2, 3

Time-Based Treatment Algorithm

0-3 Hours from Symptom Onset (STRONGEST INDICATION)

• This is the gold standard window with Grade 1A evidence showing 154 additional favorable outcomes per 1,000 patients treated 2
• The absolute benefit is greatest when treatment is initiated earliest within this window 1
• Symptomatic intracranial hemorrhage occurs in 6.4% of tPA-treated patients versus 0.6% of placebo patients, but the benefit substantially outweighs this risk 1, 4

3-4.5 Hours from Symptom Onset (CONDITIONAL INDICATION)

• Treatment is suggested with Grade 2C evidence, showing 69 additional favorable outcomes per 1,000 patients 2
• The American College of Chest Physicians provides conditional recommendation for this window 1, 3
• More careful patient selection is required as time increases, excluding higher-risk patients 5

Beyond 4.5 Hours (CONTRAINDICATED)

• Do not administer IV tPA beyond 4.5 hours from symptom onset (Grade 1B contraindication) 1, 2
• Consider intraarterial tPA for proximal cerebral artery occlusions within 6 hours in patients who don't meet IV tPA eligibility (Grade 2C) 2
• Mechanical thrombectomy may be considered in carefully selected patients (Grade 2C) 2

Dosing Protocol

• Total dose: 0.9 mg/kg (maximum 90 mg total) 1, 2, 3
• Administer 10% as IV bolus over 1 minute 1
• Infuse remaining 90% over 60 minutes 1
• Do not delay treatment for difficult IV access; consider alternative access methods 2
• Establish IV access in the non-paretic arm when possible 2

Special Populations and Contraindications

Minor Stroke

• Do not exclude minor strokes from treatment eligibility within the standard time windows 1
• Treatment is strongly recommended within 0-3 hours (Grade 1A) and conditionally recommended within 3-4.5 hours (Grade 2C) for minor strokes 1
• When uncertainty exists, urgently consult stroke specialist or telestroke services 1

Anticoagulated Patients

• Patients on direct oral anticoagulants (DOACs) should NOT receive tPA due to substantially elevated bleeding risk 1
• Carefully assess all patients for contraindications including evidence of intracranial hemorrhage on imaging 3

Antiplatelet Therapy

• Patients on antiplatelet therapy prior to stroke receive the same 0.9 mg/kg dose 1
• Be aware of 3% absolute increased risk of symptomatic ICH compared to those not on antiplatelet therapy 1

Post-Treatment Management

• Administer aspirin 160-325 mg within 24-48 hours after tPA (or immediately if tPA contraindicated) for patients not receiving anticoagulation (Grade 1A) 1, 2, 3
• For minor stroke or high-risk TIA, consider dual antiplatelet therapy (aspirin plus clopidogrel) for 21 days when initiated within 12-24 hours 1
• Use prophylactic-dose subcutaneous LMWH for VTE prophylaxis in patients with restricted mobility (Grade 2B) 2, 3

Outcome Assessment

• Use the National Institutes of Health Stroke Scale (NIHSS) to assess stroke severity, with lower baseline scores predicting more favorable outcomes 2
• Measure outcomes at 3 months using Modified Rankin Scale (mRS), with 0-1 indicating very favorable outcome and 0-2 indicating functional independence 2
• Patients with mild to moderate strokes (NIHSS <20) and those <75 years have greatest potential for excellent outcomes, though this does not exclude older or more severe stroke patients 1

Critical Pitfalls to Avoid

• The baseline symptomatic intracranial hemorrhage rate is 4-6% with proper dosing, which increases substantially with dosing errors 1
• Patient selection is crucial to minimize hemorrhagic complications 3
• As time from symptom onset increases, the need for careful patient selection also increases 5