Protamine Sulphate (Heparin Reversal)

How it works

Protamine is a strongly basic protein that binds electrostatically to acidic heparin to form an inactive stable complex, abolishing heparin's antithrombin-mediated anticoagulant activity; it only partially reverses low-molecular-weight heparins.

Prescribing in practice

• Inject slowly because rapid administration can cause severe hypotension, bradycardia, anaphylactoid reactions and pulmonary hypertension; have resuscitation facilities available.
• Patients exposed to protamine-containing insulins, those with fish allergy and men who are infertile or have had a vasectomy are at higher risk of hypersensitivity.
• Excessive protamine has its own anticoagulant effect, and rebound anticoagulation (heparin rebound) can occur after cardiac surgery; titrate the dose to the heparin to be neutralised.

Monitoring

Monitor blood pressure, heart rate and coagulation parameters such as the activated clotting time or APTT during and after administration to confirm reversal and detect rebound.

Counselling the patient

• Inform the team if you have a fish allergy, take a protamine-containing insulin or have had a vasectomy.
• Report any breathlessness, flushing or feeling faint during the injection.

Evidence & guidelines

Protamine reversal of heparin is standard practice in cardiac surgery and established prescribing references, with MHRA-recognised risks of serious cardiovascular and hypersensitivity reactions on rapid administration.