What is the protocol for heparin (anticoagulant) reversal?

Heparin Reversal Protocol

Immediate Reversal Strategy

For patients requiring urgent heparin reversal (particularly with active bleeding or intracranial hemorrhage), administer IV protamine sulfate at 1 mg for every 100 units of heparin given in the previous 2-3 hours, with a maximum single dose of 50 mg, delivered slowly over 10 minutes. 1

Standard Dosing Algorithm

Time-Based Protamine Calculation

The protamine dose must be adjusted based on timing since last heparin administration, as heparin has an approximate half-life of 30 minutes: 2

• If heparin given within 30 minutes: Full calculated dose (1-1.3 mg protamine per 100 units heparin) 3, 2
• If heparin given 30-60 minutes prior: Reduce to 0.5-0.75 mg per 100 units 3
• If heparin given 60-120 minutes prior: Reduce to 0.375-0.5 mg per 100 units 3
• After 3-5 half-lives (>2-3 hours): Protamine likely not needed 1

Specific Dosing for Full-Dose Heparin Infusion

Calculate the total heparin units administered in the preceding 2-3 hours only (not the entire cumulative dose), then administer 1 mg protamine per 100 units, maximum 50 mg per single dose. 1

Administration Protocol

Critical Administration Guidelines

• Administer by slow IV injection over 10 minutes minimum to prevent severe hypotension, bradycardia, and anaphylactoid reactions 1, 3, 2
• Never exceed 50 mg in any 10-minute period 2
• Have resuscitation equipment immediately available before administration, as fatal anaphylaxis-like reactions have been reported 2

Post-Administration Monitoring

Measure aPTT or ACT 5-10 minutes after protamine administration to confirm adequate reversal: 1, 3

• If aPTT/ACT remains elevated, administer additional protamine at 0.5 mg per 100 units of unfractionated heparin 1
• Repeat monitoring after each additional dose 1, 3

Context-Specific Modifications

Prophylactic Subcutaneous Heparin

• Do NOT routinely reverse prophylactic subcutaneous heparin 1
• Consider reversal only if aPTT is significantly prolonged 1

Cardiac Surgery with Cardiopulmonary Bypass

For operations with CPB duration <90 minutes, the fixed-dose ratio method (1.0-1.3 mg per 100 units) is appropriate. 1, 3 For longer CPB durations, use ACT-guided heparin dose-response curve methods or heparin-protamine titration to minimize protamine exposure. 1

Recent evidence suggests a fixed 250 mg dose may be comparable to ratio-based dosing in cardiac surgery patients, potentially conserving protamine without compromising reversal efficacy. 4 However, this applies specifically to post-CPB scenarios with standardized heparin protocols.

Critical Safety Considerations

High-Risk Populations for Protamine Reactions

Patients at increased risk for severe hypersensitivity reactions include: 5

• Prior protamine exposure
• Fish allergies
• Vasectomized or infertile men
• Diabetics on protamine-containing insulin (NPH)

Protamine Paradox

Excess protamine has intrinsic anticoagulant properties and may paradoxically worsen bleeding at high doses. 5, 4 This reinforces the importance of time-based dose reduction and avoiding empiric "full reversal" dosing without considering heparin metabolism.

Low Molecular Weight Heparin (LMWH) Reversal

While the question focuses on unfractionated heparin, LMWH reversal differs significantly:

Enoxaparin-Specific Protocol

• If given within 8 hours: 1 mg protamine per 1 mg enoxaparin (max 50 mg) 1, 5
• If given 8-12 hours prior: 0.5 mg protamine per 1 mg enoxaparin (max 50 mg) 1, 5
• Administer over 10 minutes 1, 5

Important caveat: Protamine only partially reverses LMWH anti-Xa activity (approximately 60-75% neutralization), and clinical effectiveness is variable. 6 Anti-Xa levels are useful before protamine but unhelpful for monitoring reversal effect. 6

Common Pitfalls to Avoid

1. Calculating protamine based on total cumulative heparin dose rather than only the dose given in the preceding 2-3 hours 1, 3
2. Rapid IV push administration leading to cardiovascular collapse 2
3. Administering >50 mg in a single dose or 10-minute period 1, 2
4. Failing to reduce dose for time elapsed since heparin administration 3, 2
5. Routinely reversing prophylactic doses without clinical indication 1