When to hold aspirin (acetylsalicylic acid) in cases of hemorrhagic transformation?

When to Hold Aspirin in Hemorrhagic Transformation

In patients with hemorrhagic transformation after ischemic stroke, aspirin should be continued in most cases, particularly for hemorrhagic infarction (HI), but temporarily held for 1-2 weeks in cases of parenchymal hematoma type 2 (PH-2) with significant mass effect or clinical deterioration. 1, 2

Risk Stratification by Hemorrhagic Transformation Subtype

The decision to hold aspirin depends critically on the type of hemorrhagic transformation identified on imaging:

Hemorrhagic Infarction (HI-1 and HI-2)

• Continue aspirin at the lowest effective dose (75-100 mg daily) with mandatory proton pump inhibitor co-therapy 2
• Hemorrhagic infarction represents petechial bleeding along the margins of infarction and does not typically expand 3
• Early continuation of aspirin prevents recurrent ischemic stroke without causing worsening of HI 4
• The mortality benefit from aspirin in established cardiovascular disease substantially outweighs bleeding risk when appropriate gastroprotection is provided 2

Parenchymal Hematoma (PH-1 and PH-2)

• Temporarily hold aspirin for 1-2 weeks in cases of PH-2 (confluent hematoma >30% of infarct volume with mass effect) 1, 2
• For PH-1 (small confluent hematoma without mass effect), aspirin may be continued with close monitoring 4
• Delaying anticoagulation and antiplatelet therapy should be considered for patients at high risk of hemorrhagic complications, including those with extensive infarct burden or evidence of significant hemorrhagic transformation 1
• Reinitiation of aspirin within 7-14 days appears safe and does not exacerbate PH 4

Timing of Aspirin Resumption After Holding

When aspirin has been held due to significant hemorrhagic transformation:

• Resume aspirin between 7-14 days after the acute hemorrhagic event when considered safe from the perspective of hemorrhagic transformation 1, 4
• Earlier resumption (within 7 days) can be considered for patients at low risk of bleeding complications, such as those with small infarct burden and minimal hemorrhage on imaging 1
• The later the resumption of antithrombotic therapy, the higher the frequency of recurrent ischemic stroke, making early reinitiation desirable when safe 4

Dose Optimization to Minimize Bleeding Risk

When continuing or resuming aspirin in patients with hemorrhagic transformation:

• Use 75-100 mg daily rather than higher doses, as this provides equivalent cardiovascular protection while minimizing bleeding risk 1, 2
• Reducing aspirin dose from 300 mg to 75 mg daily reduces bleeding risk by 40% 2
• In patients at high risk for hemorrhagic transformation (predictive score ≥3), higher aspirin doses (300 mg) are associated with increased risk of PH-2 compared to lower doses (200 mg or less) 5
• Mandatory gastroprotection with proton pump inhibitor therapy should be provided for all patients with hemorrhagic transformation on aspirin 2

Critical Clinical Scenarios Requiring Aspirin Discontinuation

Aspirin should be discontinued in specific high-risk situations:

• Recent intracranial hemorrhage with active bleeding: discontinue for minimum 1-2 weeks 2
• Severe thrombocytopenia (<50,000/μL) 2
• Clinical deterioration from mass effect with signs of brainstem compression, including ipsilateral pupillary dysfunction, worsening limb power progressing to extensor posturing, or abnormal respiratory patterns 1

Management of Dual Antiplatelet Therapy

For patients on combination aspirin and clopidogrel who develop hemorrhagic transformation:

• Discontinue clopidogrel but continue aspirin in most cases, as the combination increases bleeding risk 1
• Never discontinue both antiplatelet agents simultaneously in patients with coronary stents placed within the past 6-12 months (drug-eluting stents) or 4-6 weeks (bare-metal stents) 6
• If modification is required in stent patients, continue aspirin and withhold the P2Y12 inhibitor 2

Common Pitfalls to Avoid

• Do not substitute heparin or LMWH for aspirin in patients requiring antiplatelet therapy, as heparin does not prevent arterial thrombosis or stent thrombosis 6, 7
• Avoid routine discontinuation of aspirin in asymptomatic hemorrhagic transformation, as this is common (occurring in 32-36% of patients) and not associated with worse functional outcomes 3
• Do not delay aspirin resumption excessively beyond 14 days, as the risk of recurrent ischemic stroke increases significantly with prolonged interruption 4
• Intravenous heparin should be avoided in hemorrhagic transformation, but subcutaneous heparin or low-molecular-weight heparin is necessary for DVT prophylaxis even with some hemorrhagic conversion 1