Heparin Antidote — Vascular / Cardiac Surgery Pregnancy: Use with caution — limited data; use if clearly necessary for life-threatening heparin reversal

Protamine Sulphate

Brand names: Protamine Sulphate Injection

Adult dose

Dose: UFH reversal: 1 mg neutralises approximately 80–100 units UFH; give slowly IV over 10 minutes; LMWH partial reversal: 1 mg per 100 anti-Xa units of LMWH (e.g., 1 mg per 1 mg enoxaparin)

Route: Intravenous — SLOW infusion (rate <5 mg/min)

Frequency: Single dose (UFH); may repeat for rebound heparin effect

Max: 50 mg per single dose; total dose guided by anti-Xa/aPTT

Calculate UFH dose given in last 2–2.5 hours only (heparin cleared over time — reduce protamine accordingly). IV must be given SLOWLY — rapid injection causes severe hypotension, bradycardia, pulmonary hypertension. LMWH: protamine neutralises anti-IIa activity completely but only ~60–80% anti-Xa activity — partial reversal. Fondaparinux: protamine ineffective.

Paediatric dose

Dose: 1 mg per 100 units UFH received mg/kg

Route: IV slow infusion

Frequency: Single dose

Max: 50 mg per dose

BNFc: same calculation as adults; used in paediatric cardiac surgery

Dose adjustments

Renal

No dose adjustment required

Hepatic

No dose adjustment required

Paediatric weight-based calculator

Patient weight (kg)

BNFc: same calculation as adults; used in paediatric cardiac surgery

Clinical pearls

Rebound heparin effect occurs 30–60 minutes after protamine as heparin redistributes from tissue depots — recheck aPTT/ACT and repeat protamine if needed
Fish allergy risk: protamine derived from salmon/trout sperm; theoretical cross-reactivity with fish allergy — have resuscitation equipment available; vasectomised males have higher antibody titres against protamine
In cardiac surgery: dose based on total heparin used during bypass minus heparin eliminated during bypass time — usually ACT-guided (target ACT <150 seconds)
LMWH reversal is incomplete — particularly anti-Xa activity (60–80%); if major bleeding on LMWH and protamine insufficient, consider andexanet alfa
Protamine itself can cause direct platelet aggregation and consumption — thrombocytopaenia can occur

Contraindications

Fish allergy (protamine derived from fish sperm — cross-reactivity risk)
Previous protamine sensitivity
Vasectomy (anti-protamine antibodies — higher reaction risk)

Side effects

Hypotension (rapid infusion)
Bradycardia
Pulmonary hypertension
Anaphylaxis / anaphylactoid reactions
Dyspnoea
Flushing
Rebound heparin effect (30–60 minutes post-dose — heparin released from tissues)
Thrombocytopaenia

Interactions

Heparin — reversal agent (intended interaction)
Insulin — some insulin formulations use protamine as NPH modifier (NPH insulin); theoretical anti-protamine antibodies in insulin users

Monitoring

ACT or aPTT (30 minutes post-dose and again at 60 minutes for rebound)
Blood pressure (continuous during infusion)
Heart rate and respiratory status
FBC (thrombocytopaenia)
Signs of anaphylaxis

Reference: BNFc; BNF 90; MHRA SPC Protamine Sulphate; British Society for Haematology LMWH Guidelines; Cardiac Surgery Anticoagulation Protocols. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways