What is the treatment for hemorrhagic conversion of a cerebrovascular disease (CVD) infarct in patients on enoxaparin (low molecular weight heparin)?

Management of Hemorrhagic Conversion in Stroke Patients on Enoxaparin

Immediately discontinue enoxaparin and administer protamine sulfate for reversal, with dosing based on timing of last enoxaparin dose and anti-Xa levels if available. 1, 2

Immediate Reversal Strategy

Protamine sulfate is the FDA-approved reversal agent for enoxaparin-associated hemorrhage, though it only partially neutralizes enoxaparin (approximately 60% reversal of anti-Xa activity). 1, 2

Dosing Algorithm for Protamine Sulfate:

• If enoxaparin given <8 hours ago: Administer 1 mg protamine per 1 mg enoxaparin (maximum 50 mg protamine per dose) 2
• If enoxaparin given 8-12 hours ago: Administer 0.5 mg protamine per 1 mg enoxaparin 2
• If enoxaparin given >12 hours ago: Consider 0.5 mg protamine per 1 mg enoxaparin if anti-Xa levels remain therapeutic (>0.5 IU/mL), as enoxaparin can accumulate in renal dysfunction 2

Critical caveat: The 25 mL vials contain 250 mg protamine (5 times more than 5 mL vials with 50 mg) and are designed for large heparin reversals during surgery—verify dosing carefully to avoid protamine overdose. 1

Withholding Anticoagulation After Hemorrhagic Transformation

Oral anticoagulation should be withheld for at least 5 days if the infarct is >35% of the cerebral hemisphere or if there is uncontrolled hypertension. 3 This recommendation balances the competing risks:

• Risk of recurrent embolism in first 2 weeks: Lower than risk of hemorrhagic transformation in large infarcts 3
• Hypertension control is mandatory before restarting any anticoagulation 3
• Repeat CT scan must show no hemorrhagic transformation before considering anticoagulation resumption 3

Bridging Strategy During Anticoagulation Hold

If there is high thrombotic risk (e.g., left atrial thrombus, mechanical valve, or ongoing indication for anticoagulation), intravenous unfractionated heparin with aPTT 1.5-2.0 can be used as a bridge after the acute hemorrhagic period stabilizes. 3 This allows for rapid reversal if bleeding worsens, unlike enoxaparin which has prolonged activity.

Monitoring Considerations

Check anti-Xa levels if available, particularly if:

• Enoxaparin was given >12 hours prior but hemorrhage occurred 2
• Patient has renal dysfunction (enoxaparin accumulates with creatinine clearance <30 mL/min) 2
• Therapeutic anti-Xa levels (>0.5 IU/mL) justify protamine administration even beyond 12 hours 2

Supportive Management

• Blood pressure control: Essential to prevent hematoma expansion 3
• Repeat neuroimaging: CT scan to assess hemorrhage size and rule out expansion before any anticoagulation decisions 3
• Transfusion support: As needed for hemodynamic stability
• Avoid antiplatelet agents: Do not restart aspirin or other antiplatelets during the acute hemorrhagic phase 3

When to Resume Anticoagulation

After at least 5 days, anticoagulation may be cautiously resumed only if:

• Repeat CT shows no hemorrhagic expansion 3
• Blood pressure is controlled 3
• The thrombotic indication remains compelling (e.g., mechanical valve, atrial fibrillation with high stroke risk) 3

Consider switching from enoxaparin to warfarin or a direct oral anticoagulant for long-term management, as these allow for more predictable reversal strategies if future bleeding occurs. 3