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Heparin Reversal Agent Pregnancy: Use with caution — limited data; used for heparin reversal in emergency situations

Protamine Sulphate

Brand names: Prosulf

Adult dose

Dose: 1 mg per 100 units of heparin to be neutralised; max 50 mg IV
Route: IV slow injection (max 5 mg/min)
Frequency: Single dose; may repeat if heparin rebound
Max: 50 mg per dose
Post-cardiac surgery: typically 1 mg per 100 units of heparin given intraoperatively. Give slowly over 10 minutes to avoid haemodynamic reactions. If >30 min since heparin given, reduce dose by 50%. Excess protamine causes paradoxical anticoagulation.

Paediatric dose

Route:
Seek specialist opinion — dose calculated per heparin received (same 1:100 unit ratio). Used in paediatric cardiac surgery under perfusionist/anaesthetic specialist guidance.

Dose adjustments

Renal

No dose adjustment required — titrate by effect.

Hepatic

No specific adjustment required.

Clinical pearls

  • Fish allergy significantly increases anaphylaxis risk — have resuscitation drugs ready (adrenaline, hydrocortisone, antihistamine)
  • Heparin rebound: heparin sequestered in tissues re-enters circulation after protamine is metabolised — monitor ACT 30–60 min post-reversal in cardiac surgery; may need second small dose
  • Excess protamine causes paradoxical anticoagulation — dose precision is critical; never exceed 1 mg/100 units heparin given

Contraindications

  • Fish allergy (protamine derived from fish sperm — anaphylaxis risk)
  • Previous protamine allergy
  • Vasectomised men (anti-protamine antibodies — increased reaction risk)

Side effects

  • Anaphylaxis/anaphylactoid reaction (potentially severe)
  • Hypotension
  • Bradycardia
  • Pulmonary hypertension (IV histamine release)
  • Paradoxical anticoagulation (excess protamine)
  • Heparin rebound (protamine metabolised before heparin — monitor ACT post-bypass)

Interactions

  • Heparin (specific reversal)
  • Low molecular weight heparins (only 60–75% reversal — protamine less effective for LMWH)

Monitoring

  • ACT (activated clotting time) before and after in cardiac surgery
  • Haemodynamic monitoring during infusion (anaphylaxis surveillance)
  • Check for heparin rebound 30–60 min post-bypass

Reference: BNFc; BNF 90; AAGBI Guidelines; Society of Thoracic Surgeons Guidelines on Anticoagulation. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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