When to use tissue plasminogen activator (tPA) versus clot retrieval in acute ischemic stroke management?

tPA vs Mechanical Thrombectomy: Treatment Selection Algorithm

For acute ischemic stroke, use IV tPA as first-line therapy within 4.5 hours of symptom onset for eligible patients, and add mechanical thrombectomy for large vessel occlusions—these are complementary, not competing therapies. 1, 2

Primary Treatment Framework

The provided evidence focuses exclusively on tPA thrombolysis and does not contain guidelines comparing tPA to mechanical thrombectomy. However, the treatment algorithm can be structured based on time windows and clinical scenarios:

Time-Based tPA Administration

0-3 Hours from Symptom Onset:

• Administer IV tPA (0.9 mg/kg, maximum 90 mg) immediately if the patient meets NINDS inclusion/exclusion criteria—this is a Level A recommendation with the strongest evidence. 3
• Give 10% as IV bolus over 1 minute, followed by 90% infused over 60 minutes. 1, 2
• This provides an absolute benefit of 12% more patients achieving minimal or no disability (NNT=8). 3
• Symptomatic intracranial hemorrhage risk increases to 6.4% versus 0.6% with placebo (NNH=17). 3, 4

3-4.5 Hours from Symptom Onset:

• Offer IV tPA to carefully selected patients meeting ECASS III criteria—this is a Level B recommendation with more conditional support. 3
• Use the same dosing protocol (0.9 mg/kg, maximum 90 mg). 1
• Benefit is smaller: NNT=14 for favorable outcome, with symptomatic ICH risk of NNH=23. 3
• The American College of Chest Physicians gives this a Grade 2C recommendation, indicating weaker evidence. 2, 5

Beyond 4.5 Hours:

• Do not administer IV tPA—this is a Grade 1B recommendation against use. 1, 6
• Consider intraarterial thrombolysis for proximal cerebral artery occlusions within 6 hours (Grade 2C). 2, 6

Critical Decision Points

When tPA Alone May Be Insufficient

Large Vessel Occlusions:

• The guidelines mention mechanical thrombectomy as an option for carefully selected patients with proximal arterial occlusions, particularly when presenting within 6-12 hours with favorable imaging. 6
• This represents a complementary approach rather than an either/or decision—eligible patients should receive tPA first without delaying door-to-needle time. 7

Multifocal Infarcts:

• Proceed with tPA if combined infarct volume does not exceed one-third of MCA territory equivalent across all lesions. 6
• Assess for hemorrhagic transformation using imaging—HI1 (small petechiae) allows cautious proceeding, while HI2, PH1, or PH2 contraindicate thrombolysis. 6

Institutional Readiness Requirements

Systems-Based Prerequisites:

• Only administer tPA at institutions with established systems to safely deliver the medication—the effectiveness is less established without proper infrastructure. 3
• Target door-to-needle time ≤60 minutes, as this correlates with lower mortality (adjusted OR 0.78) and less symptomatic ICH (4.7% vs 5.6%). 7
• Higher annual volumes of tPA-treated patients correlate with better adherence to time targets. 7

Common Pitfalls and Contraindications

Absolute Contraindications:

• Never give tPA to patients on direct oral anticoagulants (DOACs) like apixaban due to substantially elevated bleeding risk. 1
• Hemorrhagic transformation (HI2 or higher) in existing infarcts. 6
• Extensive early ischemic changes (>1/3 MCA territory). 6

Relative Risk Considerations:

• Patients on antiplatelet therapy have 3% absolute increased risk of symptomatic ICH but can still receive tPA at standard dosing. 1
• Baseline symptomatic ICH rate is 4-6% with proper dosing, increasing substantially with dosing errors. 1
• tPA does not alter 90-day mortality, only functional outcomes. 3

Post-Treatment Management

Immediate Monitoring:

• Watch closely for symptomatic ICH in the first 36 hours. 1, 6
• Delay antiplatelet therapy for 24 hours after tPA administration. 6

Adjunctive Antiplatelet Therapy:

• Administer aspirin 160-325 mg within 24-48 hours for patients not receiving anticoagulation (Grade 1A). 2, 6, 5
• For minor stroke or high-risk TIA, consider dual antiplatelet therapy (aspirin plus clopidogrel) for 21 days when initiated within 12-24 hours. 1

Shared Decision-Making

Risk-Benefit Discussion:

• Engage in shared decision-making with patients/surrogates before administering tPA, discussing both benefits and harms. 3
• Patients tend to overestimate benefits and underestimate harms associated with symptomatic ICH—provide realistic expectations. 3
• The absolute benefit is greatest with earliest treatment, with proportional benefit decreasing over time. 1

Stroke Severity Considerations:

• Patients with NIHSS 5-22 show the most benefit from tPA. 3
• Mild to moderate strokes (NIHSS <20) and patients <75 years have greatest potential for excellent outcomes, though this does not exclude older patients or those with more severe strokes. 1