Protamine sulfate

How it works

Being strongly basic, protamine binds tightly to acidic heparin to form an inactive stable complex, thereby reversing heparin-induced anticoagulation; it also has partial activity against low molecular weight heparins.

Prescribing in practice

• Rapid intravenous injection can cause severe hypotension, bradycardia and anaphylactoid or pulmonary hypertensive reactions, so administer slowly with facilities for resuscitation available.
• Excess protamine relative to circulating heparin can itself have an anticoagulant effect, so the dose must be titrated to the amount of heparin to be neutralised.
• The risk of serious hypersensitivity is increased in patients exposed to protamine-containing insulins, those with fish allergy and previously vasectomised or infertile men.

Monitoring

Monitor blood pressure, heart rate and clotting (such as activated clotting time or APTT) during and after administration to confirm reversal and guide dosing.

Counselling the patient

• Explain to the team that protamine is being given to reverse heparin and that blood pressure and heart rate are being watched for reactions.
• Note any history of fish allergy or previous protamine or protamine-insulin exposure before administration.

Evidence & guidelines

Protamine is the established agent for reversing heparin anticoagulation, with only partial neutralisation of low molecular weight heparins and minimal effect on fondaparinux.