Is aspirin safe to administer in the acute phase of a patient with a malignant large‑territory cerebral infarct after confirming no hemorrhagic transformation on imaging?

Aspirin Administration in Malignant Cerebral Infarction

Yes, aspirin should be administered in malignant cerebral infarction after confirming absence of hemorrhagic transformation on imaging, using a loading dose of 160–325 mg within 24–48 hours of symptom onset, followed by 75–100 mg daily for long-term secondary prevention. 1, 2

Immediate Assessment Requirements

• Obtain urgent non-contrast CT or MRI to exclude intracranial hemorrhage before any antiplatelet agent is given. This is an absolute prerequisite mandated by all major stroke guidelines. 1, 2

• If the patient received intravenous alteplase, delay aspirin for at least 24 hours post-thrombolysis and obtain repeat neuroimaging to confirm absence of hemorrhagic transformation before starting antiplatelet therapy. 1, 2

• For patients who did not receive thrombolysis, administer aspirin within 24–48 hours once imaging excludes hemorrhage. 1, 2

Loading and Maintenance Dosing Protocol

• Loading dose: 160–325 mg (non-enteric coated) administered within the first 24–48 hours to achieve rapid platelet inhibition. 1, 2

• Maintenance dose: 75–100 mg daily starting on day 2 and continued indefinitely for secondary stroke prevention. 1, 2

• Avoid enteric-coated aspirin for the loading dose because it has a slower onset of action. 1

Evidence Supporting Use in Large Strokes

• Grade 1A evidence from the International Stroke Trial (IST) and Chinese Acute Stroke Trial (CAST), encompassing approximately 40,000 patients, demonstrates that aspirin 160–300 mg within 48 hours reduces death or dependency, preventing 13 events per 1,000 treated. 1, 2

• The same pooled data show a reduction of 7 per 1,000 in recurrent ischemic stroke and a net decrease of 9 per 1,000 in the overall risk of further stroke or death. 1, 2

• Aspirin reduces mortality during the 28-day treatment period in acute ischemic stroke. 2

Special Considerations for Malignant Infarcts

• In the presence of a large cerebral infarction, European Society of Cardiology guidelines recommend considering a delay in anticoagulation initiation (not aspirin) given the risk of hemorrhagic transformation. 3

• For malignant infarcts specifically, aspirin remains indicated but requires heightened vigilance for hemorrhagic transformation, which occurs in approximately 0.1% of patients as an absolute increase. 2

• High-risk features that warrant particular caution include lobar infarct location, advanced age, presence of microbleeds on gradient echo MRI, and severe stroke (high NIHSS score). 2

Management of Hemorrhagic Transformation

• If hemorrhagic transformation is detected on imaging:
  • For minor hemorrhagic transformation (HI1 - small petechiae along infarct margins): aspirin 160–325 mg can be started within 24–48 hours after confirming no progression of bleeding on follow-up imaging. 4
  • For higher-grade hemorrhagic transformation (HI2, PH1, PH2 - confluent petechiae, blood clots, or parenchymal hemorrhage): discontinue all antiplatelets for at least 7–10 days (1–2 weeks). 4
  • After 7–10 days, if no expansion of hemorrhage is noted on repeat imaging, consider restarting with a single antiplatelet agent (aspirin) rather than dual therapy. 4

Absolute Contraindications

• Intracranial hemorrhage not excluded on neuroimaging 1, 2

• Administration within 24 hours of IV thrombolysis due to significantly increased risk of serious intracranial bleeding complications 1, 2

• Active major bleeding or severe thrombocytopenia 1

• Known hypersensitivity to aspirin 1

Critical Pitfalls to Avoid

• Never use aspirin as a substitute for IV thrombolysis or mechanical thrombectomy in eligible patients—aspirin is not an acute recanalization therapy and delays definitive treatment. 1, 2

• Never combine aspirin with urgent anticoagulation in moderate-to-severe strokes due to unacceptably high intracranial hemorrhage risk. 2

• Do not delay aspirin beyond 48 hours in patients without contraindications, as early administration (within 24–48 hours) is when maximal benefit is demonstrated. 1, 2

• Avoid dual antiplatelet therapy (aspirin plus clopidogrel) in the acute setting of large/malignant strokes, as bleeding risk outweighs benefit; dual therapy is reserved for minor strokes (NIHSS ≤3) only. 1, 2

• Do not use glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban) in acute ischemic stroke, as they are potentially harmful. 1

Alternative Routes for Patients Unable to Swallow

• For patients with dysphagia: aspirin 325 mg administered rectally or aspirin 81 mg via nasogastric/enteral tube are reasonable alternatives. 1

• Avoid enteric-coated formulations for loading doses via enteral routes. 1

Long-Term Management After Malignant Infarct

• Continue aspirin 75–100 mg daily indefinitely for secondary stroke prevention. 1, 2

• If a cardioembolic source (e.g., atrial fibrillation) is identified, transition to oral anticoagulation rather than antiplatelet therapy after the acute period. 1

• Monitor closely for signs of neurological deterioration in the first 24–72 hours after antiplatelet initiation. 1