Protamine was originally isolated from the sperm of salmon and other species of fish but is now produced primarily through recombinant biotechnology. It is a highly cationic peptide that binds to either heparin or low molecular weight heparin (LMWH) to form a stable ion pair which does not have anticoagulant activity. The ionic complex is then removed and broken down by the reticuloendothelial system. In large doses, protamine sulfate may also have an independent—however weak—anticoagulant effect.
Dosage for heparin reversal is 1.0 - 1.5 mg protamine sulfate IV for every 100 IU of active heparin, not to exceed 50 mg. PTT should be monitored at 5–15 minutes after dose then in 2–8 hours afterward. In patients who are allergic to fish, it can cause significant histamine release resulting in hypotension and bronchoconstriction. It may also cause pulmonary hypertension. Infusion should be slow to minimize these side effects.
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, protein purification and in tissue cultures as a crosslinker for viral transduction.
In gene therapy, protamine sulfate has been studied as a means to increase transduction rates by both viral and nonviral (e.g. utilizing cationic lipids) mediated delivery mechanisms.