How do you reverse the anticoagulant effects of heparin (unfractionated heparin) in a patient with significant bleeding or requiring urgent surgery?

Heparin Reversal Protocol

Unfractionated heparin (UFH) should be reversed with protamine sulfate at a dose of 1 mg per 100 units of heparin administered in the previous 2-3 hours, with a maximum single dose of 50 mg given by slow IV infusion over 10 minutes. 1, 2

Dosing Algorithm for Protamine Administration

For Active Bleeding or Emergency Surgery

1. Calculate protamine dose:

   • 1 mg protamine per 100 units of heparin given in the previous 2-3 hours 1, 2
   • Maximum single dose: 50 mg 2

2. Adjust for time since last heparin dose:

   • If >30 minutes since heparin administration, reduce dose by considering heparin's half-life of approximately 30 minutes 2
   • For example:
     • <30 minutes: full calculated dose
     • 30-60 minutes: 50-75% of calculated dose
     • 60-120 minutes: 25-50% of calculated dose

     • 120 minutes: 25% of calculated dose

3. Administration method:

   • Administer by slow IV infusion over 10 minutes to minimize adverse effects 1
   • Never give more than 50 mg in any 10-minute period 2

Monitoring Effectiveness

1. Check activated partial thromboplastin time (aPTT) or activated clotting time (ACT) 5-10 minutes after protamine administration 1

2. If coagulation parameters remain elevated or bleeding continues:

   • Consider additional protamine at 0.5 mg per 100 units of heparin initially given 1
   • Reassess aPTT/ACT after additional dose

Special Considerations

Low Molecular Weight Heparin (LMWH) Reversal

• Protamine only partially reverses LMWH (approximately 60-75% of anti-Xa activity) 1, 3, 4
• For enoxaparin: 1 mg protamine per 1 mg of enoxaparin if given within 8 hours (maximum 50 mg) 1
• For dalteparin/nadroparin/tinzaparin: 1 mg protamine per 100 anti-Xa units of LMWH (maximum 50 mg) 1

Potential Adverse Effects of Protamine

• Hypotension, bradycardia, and anaphylactoid reactions can occur, especially with rapid administration 2
• Excess protamine itself can induce a coagulopathy 5, 6
• Should be given only when resuscitation techniques and treatment for anaphylactoid shock are readily available 2

Common Pitfalls and Caveats

1. Overdosing protamine: Excessive protamine can paradoxically worsen coagulopathy by inhibiting factor V activation and reducing thrombin generation 6

2. Inadequate monitoring: Failure to check coagulation parameters after reversal may lead to inadequate heparin neutralization or protamine excess

3. Expecting complete reversal of LMWH: Protamine only partially reverses LMWH, with approximately 60-75% of anti-Xa activity neutralized 3, 4

4. Rapid administration: Giving protamine too quickly increases risk of severe hypotension and anaphylactoid reactions 2

5. Ineffective for pentasaccharides: Protamine is NOT effective for fondaparinux and should not be used for its reversal 1

The evidence strongly supports using protamine as the standard agent for UFH reversal, with careful attention to dosing based on the timing of the last heparin dose. While protamine has limitations, particularly for LMWH reversal, it remains the most effective and well-established option for managing heparin-associated bleeding.