What is the recommended approach for heparin (unfractionated heparin) reversal?

Heparin Reversal Protocol

Protamine sulfate is the recommended agent for unfractionated heparin reversal, administered at a dose of 1 mg for every 100 units of heparin given in the previous 2-3 hours, with a maximum single dose of 50 mg. 1, 2

Dosing and Administration Protocol

For Unfractionated Heparin (UFH) Reversal:

• Calculate protamine dose based on heparin administered in the previous 2-3 hours:

  • 1 mg protamine per 100 units of heparin 3, 2, 1
  • Maximum single dose: 50 mg 1
  • Administer by slow IV infusion over approximately 10 minutes to minimize adverse effects 2

• Monitor effectiveness:

  • Check activated partial thromboplastin time (aPTT) or activated clotting time (ACT) 5-10 minutes after protamine administration 3, 2
  • If coagulation parameters remain elevated, consider additional protamine at 0.5 mg per 100 units of heparin 3, 2

Time Considerations:

• The required protamine dose decreases over time as heparin is metabolized 1
• Heparin has an approximate half-life of 30 minutes after IV injection 1
• For heparin administered >3 hours prior, consider reduced protamine dosing

Special Situations

Prophylactic Subcutaneous Heparin:

• Routine reversal is not recommended 3, 2
• Consider reversal only if aPTT is significantly prolonged or active bleeding is present 2

Intracranial Hemorrhage:

• Urgent reversal is recommended when intracranial hemorrhage develops during full-dose heparin infusion 3
• Follow standard protamine dosing protocol as above 3

Monitoring and Safety Considerations

Potential Adverse Effects:

• Protamine can cause severe hypotension, bradycardia, and anaphylactoid reactions 1
• Fatal reactions resembling anaphylaxis have been reported 1
• Administer only when resuscitation techniques and treatment for anaphylactic shock are readily available 1

Important Caveats:

1. Protamine itself has mild anticoagulant properties at high doses, so excessive dosing should be avoided 3
2. Protamine is less effective for reversing low molecular weight heparins (only reverses about 60% of anti-Xa activity) 4, 5
3. Protamine has negligible effects on pentasaccharides like fondaparinux 4

Alternative Agents

For situations where protamine is contraindicated or unavailable:

• No well-established alternatives exist for UFH reversal
• Recombinant factor VIIa has been suggested in some cases, but evidence is limited and it's not FDA-approved for this indication

By following this protocol, clinicians can effectively reverse the anticoagulant effects of unfractionated heparin while minimizing the risk of adverse events associated with protamine administration.