What is the recommended dose and administration of protamine sulphate for reversing heparin (unfractionated heparin) anticoagulation?

Protamine Sulfate Dosing for Unfractionated Heparin Reversal

For unfractionated heparin reversal, protamine sulfate should be 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, delivered by slow IV injection over 10 minutes. 1, 2

Dosing Algorithm for Protamine Sulfate

Primary Dosing Strategy

• Administer 1 mg of protamine sulfate for every 100 units of unfractionated heparin given in the previous 2-3 hours 1
• Maximum single dose should not exceed 50 mg 1, 2, 3
• Administer by slow intravenous injection over a period of approximately 10 minutes to avoid adverse reactions 1, 2

Time-Adjusted Dosing

• If heparin was discontinued 30-60 minutes before protamine administration, use 0.5-0.75 mg protamine per 100 units of heparin 1
• If heparin was discontinued 60-120 minutes before protamine administration, use 0.375-0.5 mg protamine per 100 units of heparin 1
• If heparin was discontinued >120 minutes before protamine administration, use 0.25-0.375 mg protamine per 100 units of heparin 1
• For heparin infusion stopped >30 minutes but <2 hours, use half the calculated protamine dose 1
• For heparin infusion stopped >2 hours but <4 hours, use a quarter of the calculated protamine dose 1

Monitoring and Additional Dosing

• Monitor activated partial thromboplastin time (aPTT) 5-10 minutes after protamine administration to confirm adequate reversal 1
• If aPTT remains elevated, administer additional protamine at a dose of 0.5 mg per 100 units of unfractionated heparin 1
• The dosage of protamine should always be guided by blood coagulation studies 2

Special Considerations

Administration Precautions

• Protamine sulfate is intended for injection without further dilution; however, if dilution is desired, D5W or normal saline may be used 2
• Diluted solutions should not be stored as they contain no preservative 2
• Protamine should not be mixed with other drugs without knowledge of their compatibility 2

Safety Concerns

• Rapid administration can cause severe systemic hypotension 1
• At higher doses, protamine itself has anticoagulant properties that can paradoxically increase bleeding risk 4
• Protamine has been shown to down-regulate thrombin generation by inhibiting factor V activation, which may contribute to increased bleeding risk 4

Clinical Effectiveness

• Protamine completely reverses the effects of unfractionated heparin but only partially reverses low molecular weight heparin (LMWH) 5, 6
• The effectiveness of protamine for LMWH reversal is dependent on the molecular weight of the LMWH components, with larger molecules being more effectively neutralized 7

This evidence-based approach to protamine dosing for unfractionated heparin reversal prioritizes patient safety while ensuring effective anticoagulation reversal to minimize bleeding complications.