Hematological Agents

Description: Protamine sulfate, a protein derived from fish sperm, is a chemical antagonist of heparin. Clinically, protamine is indicated for heparin overdose and is commonly used to neutralize heparin during extracorporeal circulation following dialysis, and arterial or cardiac surgery. Protamine was approved by the FDA in December 1948.

Mechanism of Action: Protamine possesses weak anticoagulant effects when administered alone; however, upon contact with heparin, it forms a salt, neutralizing the anticoagulant effect of both drugs. Protamine, a strongly basic compound, forms complexes with heparin sodium or heparin calcium, which are acidic compounds. Formation of this complex can result in disruption of the heparin-antithrombin III complex responsible for the anticoagulant activity of heparin. The protamine-heparin complex does not possess anticoagulant properties. Protamine's anticoagulant effect usually is clinically insignificant and is likely the result of thromboplastin inhibition, which diminishes thrombin activity.

Pharmacokinetics: Protamine is administered via intravenous infusion. The onset of action is rapid, with neutralization of heparin evident within 5 minutes. The duration of action can persist up to 2 hours, depending on body temperature. The fate of the heparin-protein complex is unknown, but it appears to be partially degraded, with the release of heparin.

Drug Information Provided by
Gold Standard Inc. � 2007

1 mg reverses approx 100 units of heparin given in the preceding 3–4 h, 50 mg max