Reversal of a heparin overdose is achieved by administration of which agent?

• A. Vitamin K
• B. Protamine sulfate
• C. Antithrombin
• D. Warfarin

Answer: (B)

Protamine sulfate neutralizes heparin directly. It is a positively charged protein that binds to the negatively charged heparin molecule, forming a stable complex with no anticoagulant activity, which rapidly reverses the bleeding tendency caused by heparin overdose. This is specific to heparin reversal, whereas vitamin K and warfarin reversal target vitamin K–dependent anticoagulation from warfarin, not heparin. Antithrombin is the natural target through which heparin exerts its effect, so giving extra antithrombin would not reverse the anticoagulation and can even influence the heparin–antithrombin interaction rather than negate it. In practice, protamine is given IV in a dose proportional to the amount of heparin previously given, with careful monitoring for adverse effects.