Protamine Sulphate

How it works

It is a strongly basic protein that binds ionically to acidic heparin molecules, forming an inactive stable complex and thereby abolishing heparin's antithrombin-mediated anticoagulant activity; it only partially reverses low molecular weight heparins.

Prescribing in practice

• Give by slow intravenous injection — rapid administration can cause severe hypotension, bradycardia, flushing and acute pulmonary hypertension, so titrate against the heparin dose still circulating and avoid excess (protamine itself has weak anticoagulant activity in overdose).
• Patients exposed to protamine-containing insulins, those with fish allergy, and men who have had a vasectomy are at higher risk of hypersensitivity and anaphylaxis, so have resuscitation facilities available.
• It only incompletely neutralises low molecular weight heparins and does not reliably reverse fondaparinux, so confirm which anticoagulant is being reversed before dosing.

Monitoring

Monitor activated partial thromboplastin time (or activated clotting time intra-operatively) to confirm reversal, alongside blood pressure, heart rate and signs of anaphylaxis during and after the injection.

Counselling the patient

• Explain this is given by a clinician to switch off the effect of a blood-thinner.
• Report any breathlessness, flushing, rash or feeling faint immediately.

Evidence & guidelines

Its use as the heparin antidote is long-established standard practice supported by the SPC, surgical anticoagulation protocols and UK guidance.