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.
It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.
Protamine sulfate is usually administered to reverse the large dose of heparin administered during certain surgeries, especially heart surgery. A dose of protamine is given when the patient is off - pump, when extracorporeal circulation and anticoagulation are no longer needed.
It is also used in gene transfer, protein purification and in tissue cultures as a crosslinker for viral transduction.
Dosage for heparin reversal is 1.0 -to- 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.
Protamine has been reported to cause allergic reactions in patients who are allergic to fish, diabetics using insulin preparations containing protamine, and vasectomized or infertile men.   These occur at rates ranging from 0.28% to 6%.  
Avoiding rapid infusion of protamine sulfate and pre-treating at-risk patients with histamine receptor antagonists (H1 and H2) and steroids may minimize these reactions. A 5-10 mg test dose is recommended following pretreatment before administering the full dose. 
- "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
- Kenneth Cornetta; W.French Anderson (1989). "Protamine sulfate as an effective alternative to polybrene in retroviral-mediated gene-transfer: implications for human gene therapy". Journal of Virological Methods. 23 (2): 187–194. doi:10.1016/0166-0934(89)90132-8. PMID 2786000.
- Sorgi, FL; Bhattacharya, S; Huang, L (Sep 1997). "Protamine sulfate enhances lipid-mediated gene transfer." (PDF). Gene therapy. 4 (9): 961–8. doi:10.1038/sj.gt.3300484. PMID 9349433.
- Walker, WS; Reid, KG; Hider, CF; Davidson, IA; Boulton, FE. (1984). "Successful cardiopulmonary bypass in diabetics with anaphylactoid reactions to protamine.". Br Heart J. 52: 112–114. doi:10.1136/hrt.52.1.112. PMID 6743419.
- Campbell, FW; Goldstein, MF; Atkins, PC. (1984). "Management of the patient with protamine hypersensitivity for cardiac surgery.". Anesthesiology. 61: 761–764. doi:10.1097/00000542-198412000-00021. PMID 6334459.
- Welsby, IJ; Newman, MF; Phillips-Bute, B; Messier, RH; Kakkis, ED. (2005). "Hemodynamic changes after protamine administration: association with mortality after coronary artery bypass surgery.". Anesthesiology. 102: 308–314. doi:10.1097/00000542-200502000-00011. PMID 15681944.