Protamine sulphate - rapid reversal of heparin
Protamine sulphate is the recognised antidote for heparin when rapid neutralisation of anticoagulation is required (major or life‑threatening bleeding, or urgent invasive procedures). This section summarises mechanism, indications, practical dosing principles, administration and monitoring, key adverse effects and operational points relevant to emergency and peri‑operative care.
Mechanism
- Protamine is a strongly basic polycation that binds and neutralises heparin by forming an inactive salt complex, abolishing heparin’s anticoagulant activity.
- Neutralisation principle: approximately 1 mg protamine neutralises 100 IU of unfractionated heparin (UFH).
- For low molecular weight heparins (LMWHs) protamine provides only partial reversal (around two‑thirds of the effect seen with UFH); incomplete neutralisation is expected.
- At higher doses protamine can exert a weak anticoagulant effect (possible interference with thromboplastin), so excess protamine may paradoxically prolong bleeding.
Indications
- Emergency reversal of UFH for life‑threatening bleeding or when rapid haemostasis is required (for example, before emergency surgery).
- Partial reversal of LMWH when clinically indicated, understanding this is incomplete.
- Treatment of accidental heparin overdose and peri‑operative reversal after heparinisation (follow local cardiac surgery protocols).
- Decision to administer should be based on clinical urgency, known heparin dose and time, available coagulation testing (ACT, aPTT, anti‑Xa, ROTEM/TEG) and specialist advice (haematology, pharmacy, NPIS).