Reversal of Lovenox (Enoxaparin) in Pregnancy
For an 80 kg pregnant woman requiring enoxaparin reversal, administer protamine sulfate at a dose of 1 mg per 1 mg of enoxaparin if given within 8 hours (maximum 50 mg single dose), or 0.5 mg per 1 mg of enoxaparin if given 8-12 hours ago, delivered by slow IV injection over 10 minutes. 1
Dosing Algorithm
The specific dose depends on timing since the last enoxaparin administration:
- Within 8 hours: Give 1 mg protamine per 1 mg enoxaparin (maximum single dose: 50 mg) 1
- 8-12 hours ago: Give 0.5 mg protamine per 1 mg enoxaparin (maximum single dose: 50 mg) 1
- Beyond 12 hours: Consider checking anti-Xa levels first, as enoxaparin may have cleared; if anti-Xa remains therapeutic, give 0.5 mg protamine per 1 mg enoxaparin 2
Example Calculation for 80 kg Patient
If this patient received therapeutic enoxaparin (1 mg/kg = 80 mg) within 8 hours, you would give 50 mg protamine (the maximum single dose, even though the calculation would be 80 mg) 1. If she received prophylactic enoxaparin (40 mg), you would give 40 mg protamine 1.
Administration Method
- Infuse protamine slowly over 10 minutes to minimize risk of severe hypotension, bradycardia, and anaphylactoid reactions 1, 3
- Monitor vital signs continuously during administration 1
Post-Administration Monitoring
- Check anti-Xa levels or aPTT 5-10 minutes after protamine to confirm adequate reversal 1
- If life-threatening bleeding persists or the patient has renal insufficiency, consider redosing with 0.5 mg protamine per 1 mg of enoxaparin 1
Critical Safety Considerations in Pregnancy
Important caveats specific to this population:
- Protamine only partially reverses the anti-Xa activity of enoxaparin (approximately 60-80% reversal), unlike its complete reversal of unfractionated heparin 4, 5
- Patients with fish allergies, prior protamine exposure, or vasectomized/infertile partners are at higher risk for hypersensitivity reactions 1, 3
- Rapid administration can cause severe hypotension and bradycardia, which is particularly dangerous in pregnancy 1, 3
- Protamine itself has weak anticoagulant properties at high doses, which may paradoxically worsen bleeding 1
Renal Function Consideration
Check renal function before dosing, as enoxaparin accumulates in renal dysfunction and may have prolonged therapeutic anti-Xa levels even 21+ hours after administration 2. This is particularly relevant in pregnancy-related conditions like preeclampsia that affect renal function.
If Protamine Fails
For life-threatening bleeding unresponsive to protamine:
- Consider activated prothrombin complex concentrates (aPCC) or recombinant factor VIIa, though evidence is limited 1
- Andexanet alfa has shown efficacy in reducing anti-Xa levels but clinical experience in pregnancy is extremely limited 1
- Transfusion support with packed red blood cells, fresh frozen plasma, and platelets as needed 4