Can we use thrombolysis with tissue plasminogen activator (tPA) in patients with acute and hyperacute multifocal infarcts?

Thrombolysis in Multifocal Acute and Hyperacute Infarcts

Multifocal infarcts are NOT an absolute contraindication to thrombolysis, but they require careful risk-benefit assessment based on total infarct burden, timing, and hemorrhagic transformation risk—proceed with tPA if the patient meets standard eligibility criteria within the appropriate time window and the combined infarct volume does not suggest extensive early ischemic changes that would increase hemorrhagic risk. 1, 2

Time-Based Treatment Algorithm

Within 3 Hours of Symptom Onset

• Strongly recommend IV tPA (0.9 mg/kg, maximum 90 mg) with 10% as bolus over 1 minute, followed by 90% infused over 60 minutes if the patient meets eligibility criteria, regardless of multifocal nature 1, 2
• The Grade 1A recommendation applies when treatment can be initiated within 3 hours 1
• Target door-to-needle time of 30 minutes (median), with 90th percentile at 60 minutes 1

Between 3-4.5 Hours of Symptom Onset

• Conditionally recommend IV tPA using the same dosing protocol if eligibility criteria are met (Grade 2C) 1, 3
• The evidence is weaker in this window, but benefit still outweighs risk in appropriately selected patients 3

Beyond 4.5 Hours

• Do NOT administer IV tPA (Grade 1B recommendation against use) 1, 3
• Initiate aspirin 160-325 mg within 48 hours instead 1, 3
• Consider intraarterial thrombolysis within 6 hours for proximal cerebral artery occlusions if IV tPA is contraindicated (Grade 2C) 1

Critical Imaging Assessment for Multifocal Infarcts

What to Look For on CT/MRI

• Assess total infarct burden across all lesions—extensive early ischemic changes involving more than one-third of the MCA territory (or equivalent combined territory) substantially increases hemorrhagic transformation risk 1
• Identify any hemorrhagic transformation in existing infarcts using the Heidelberg Classification system 4:
  • HI1 (small petechiae): May proceed with caution
  • HI2, PH1, PH2 (confluent petechiae or parenchymal hemorrhage): Delay thrombolysis for 7-10 days 4
• Obtain CTA/CTP to identify proximal arterial occlusions and assess salvageable tissue, as recommended for all acute stroke patients within treatment windows 1

Key Contraindications Specific to Multifocal Infarcts

Absolute Contraindications

• Evidence of hemorrhagic transformation (HI2 or higher grade) in any of the existing infarcts 4
• Combined infarct volume suggesting extensive early ischemic changes (>1/3 MCA territory equivalent across all lesions) 1
• Multifocal infarcts with recent onset (<7-10 days) if any show hemorrhagic transformation on imaging 4

Relative Contraindications Requiring Heightened Caution

• Multiple small acute infarcts suggesting embolic shower—consider cardioembolic source and whether anticoagulation (not thrombolysis) is more appropriate 1
• Patients on antiplatelet therapy have 3% absolute increased risk of symptomatic ICH, though this does not preclude treatment 2
• Patients on DOACs should NOT receive tPA due to substantially elevated bleeding risk 2

Alternative Treatment Considerations

When Thrombolysis is Contraindicated

• Initiate aspirin 160-325 mg within 24-48 hours for patients not receiving thrombolysis 1, 3
• Consider mechanical thrombectomy if proximal arterial occlusion is present and patient presents within 6 hours (or up to 12 hours with favorable imaging criteria) 1
• Implement VTE prophylaxis with prophylactic-dose subcutaneous LMWH or intermittent pneumatic compression for patients with restricted mobility 1, 3

Intraarterial Thrombolysis Option

• For patients with documented proximal cerebral artery occlusions who do not meet IV tPA eligibility criteria, consider IA thrombolysis within 6 hours (Grade 2C) 1
• IA thrombolysis shows increased chance of good functional outcome (RR 1.44,95% CI 1.06-1.95) despite increased symptomatic ICH risk (OR 4.7,95% CI 1.3-16) 1
• This requires specialized neurointerventional capabilities and should only be performed at centers with appropriate infrastructure 1

Common Pitfalls to Avoid

• Do not automatically exclude multifocal infarcts from thrombolysis—the pattern itself is not a contraindication if total burden is acceptable and no hemorrhagic transformation exists 1, 2
• Do not delay imaging assessment—rapid CT/CTA/CTP is essential to determine eligibility and should not be postponed due to multifocal findings 1
• Do not administer tPA if any infarct shows HI2 or higher hemorrhagic transformation—this substantially increases bleeding risk 4
• Do not exceed the 4.5-hour window based on hope that multifocal pattern might respond differently—evidence shows harm without benefit beyond this timeframe 1, 3
• Do not use tPA in patients on DOACs even if coagulation parameters appear normal—bleeding risk remains substantially elevated 2

Post-Thrombolysis Management

• Monitor closely for symptomatic ICH, which occurs in 4-6% of appropriately dosed patients but may be higher with multifocal disease 2
• Delay antiplatelet therapy for 24 hours after tPA administration 1
• If hemorrhagic transformation develops, delay antiplatelet reinitiation for 7-10 days for higher-grade bleeds (HI2, PH1, PH2) 4
• Consult stroke neurology urgently when uncertainty exists about treatment decisions in complex multifocal presentations 2

budget:token_budget Tokens used this turn: 5617 Tokens remaining: 194383