Pharmacology · Anticoagulants, Antiplatelets and Thrombolytics

A patient requires reversal of heparin after cardiac surgery. Protamine sulfate is given intravenously. Which property of protamine enables it to neutralise heparin?

  • A Protamine activates antithrombin III more strongly than heparin, displacing it from thrombin
  • B Protamine acts as a competitive inhibitor of heparin at factor Xa binding sites
  • C Protamine is a strongly positively charged protein that forms an inactive ionic complex with negatively charged heparin
  • D Protamine accelerates hepatic heparin metabolism via CYP3A4 induction
Correct answer: C. Protamine is a strongly positively charged protein that forms an inactive ionic complex with negatively charged heparin

Explanation

Heparin is a polyanionic (heavily negatively charged) sulfated polysaccharide. Protamine is a small, strongly basic (polycationic) protein derived from fish sperm; when given IV, it forms a tight ionic salt complex with heparin, neutralising its anticoagulant effect immediately. This ionic interaction is the basis of neutralisation — 1 mg protamine neutralises approximately 100 units of heparin. Protamine does not affect antithrombin III directly, inhibit factor Xa competitively, or induce CYP enzymes.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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