protamine

Mechanism: Protamine sulfate is a highly basic, arginine-rich protein that forms a stable ionic complex with the acidic heparin molecule, neutralizing its anticoagulant activity almost immediately. Heparin normally works by binding antithrombin III and accelerating its inhibition of thrombin (factor IIa) and factor Xa; protamine binding prevents heparin from interacting with antithrombin.

Clinical use: Primarily used to reverse unfractionated heparin overdose or excess anticoagulation after cardiac surgery/cardiopulmonary bypass. It only partially reverses low molecular weight heparins (LMWH like enoxaparin) because protamine binds the larger heparin chains more effectively; LMWH has reduced anti-Xa reversal. It does NOT reverse fondaparinux (a synthetic pentasaccharide) effectively.

Dosing: Given IV, typically 1 mg protamine neutralizes about 100 units of heparin, with dose adjusted based on time since heparin administration (heparin has a short half-life, so less protamine needed if time has elapsed).

Adverse effects: Can cause hypotension, bradycardia, and anaphylactoid/anaphylactic reactions, especially in patients with fish allergies, prior protamine exposure, vasectomized men (may have antibodies against sperm-related proteins), or those on NPH insulin (which contains protamine). Rapid infusion can cause pulmonary vasoconstriction and right heart failure due to thromboxane release.

High-yield boards association: Protamine sulfate = antidote for heparin overdose; contrast with vitamin K/FFP/PCC for warfarin reversal, and idarucizumab for dabigatran or andexanet alfa for factor Xa inhibitors.