Protamine sulfate

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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 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.[1]

Medical uses[edit]

Protamine sulfate is usually administered to reverse the large dose of heparin administered during certain surgeries, especially heart surgery. A dose of protamin is given when the patient is off - pump, when extracorporeal circulation is no longer needed and therefore there's no need for the anticoagulation.

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[2] and nonviral (e.g. utilizing cationic lipids)[3] mediated delivery mechanisms.


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. 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.


  1. ^ "WHO Model List of EssentialMedicines". World Health Organization. October 2013. Retrieved 22 April 2014. 
  2. ^ 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. 
  3. ^ Sorgi, FL; Bhattacharya, S; Huang, L (Sep 1997). "Protamine sulfate enhances lipid-mediated gene transfer.". Gene therapy 4 (9): 961–8. doi:10.1038/ PMID 9349433. 

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