Infarct Size Threshold for Thrombolysis
Thrombolysis should be withheld when there is extensive and clearly identifiable hypodensity on CT scan, as this indicates a large established infarct with unacceptable hemorrhagic risk. 1
Imaging-Based Exclusion Criteria
The primary determinant of "too big to thrombolyse" is based on CT findings rather than a specific volumetric measurement:
- Patients with extensive and clearly identifiable hypodensity on non-contrast CT should not receive thrombolytic therapy (Grade 1B recommendation). 1
- This CT finding indicates established infarction with increased risk of hemorrhagic transformation that outweighs potential benefits. 1
- The guideline deliberately avoids specifying an exact volume threshold, instead relying on radiographic assessment of "extensive" hypodensity. 1
Clinical Context for Decision-Making
Beyond imaging findings, several factors influence the risk-benefit calculation:
- Time from symptom onset is the most critical variable: IV tPA is strongly recommended within 3 hours (Grade 1A), conditionally recommended between 3-4.5 hours (Grade 2C), and contraindicated beyond 4.5 hours (Grade 1B). 2, 3
- Baseline stroke severity matters: Patients with mild to moderate strokes (NIHSS <20) have the greatest potential for excellent outcomes, though this does not exclude more severe strokes from consideration. 4
Hemorrhagic Risk Stratification
The decision becomes more nuanced when considering patient-specific hemorrhage risk:
- Baseline symptomatic intracranial hemorrhage rate with tPA is 4-6%, substantially higher than the 0.6% rate with placebo. 4, 5
- In the ATLANTIS trial treating patients between 3-5 hours, symptomatic ICH increased from 1.1% to 7.0% with tPA, and fatal ICH increased from 0.3% to 3.0%. 5
- Patients on anticoagulation (including DOACs like apixaban) should not receive tPA due to substantially elevated bleeding risk, regardless of infarct size. 6
Common Pitfalls to Avoid
- Do not rely on subjective estimates of "large" infarcts without clear CT hypodensity: Early ischemic changes may be subtle, and the absence of extensive hypodensity does not preclude treatment within the appropriate time window. 1
- Do not use standard coagulation tests (PT/INR, aPTT) to guide decisions in DOAC patients: These do not reliably measure anticoagulant levels. 6
- Consider mechanical thrombectomy for large vessel occlusions: Even when tPA is contraindicated due to infarct size or other factors, endovascular therapy may still be appropriate. 6
Alternative Approaches for Large Infarcts
When extensive hypodensity precludes thrombolysis:
- Initiate aspirin 160-325 mg within 24-48 hours after excluding intracranial hemorrhage. 2, 4
- Pursue mechanical thrombectomy consultation urgently if large vessel occlusion is identified on CT angiography, as this remains viable even when tPA is contraindicated. 6
- Implement prophylactic measures: For patients with restricted mobility, use prophylactic-dose subcutaneous heparin (preferably LMWH) or intermittent pneumatic compression devices. 3