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Protamine sulfate is a drug that reverses the anticoagulant effects of heparin by binding to it.

Protamine was originally isolated from the sperm of sharks and other species of fish but is now produced primarily through recombinant biotechnology. It is a highly cationic peptide. It binds to heparin to form a stable ion pair which does not have anticoagulant activity; on its own, protamine has a weak anticoagulant effect. The complex of heparin and protamine is then removed and broken down by the reticuloendothelial system.



Dosage for heparin reversal is 1mg protamine sulfate i.v. for every 100 IU of active heparin. In patients who are allergic to fish, it can cause significant histamine release resulting in hypotension and bronchoconstriction, and also causes pulmonary hypertension. Infusion should be slow to minimize these side effects. In large doses, protamine itself has some anticoagulant effect.


Protamine sulfate is usually administered to reverse the large dose of heparin administered during certain surgeries, especially heart surgery. It is also used in gene transfer and protein purification. It is also used in tissue cultures as a crosslinker for viral transduction.

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