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

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.

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

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.

Adverse effects

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. [4] [5] These reactions may manifest as urticaria, hypotension, pulmonary hypertension, bronchoconstriction, facial numbness, and cardiovascular collapse [6] and occur at rates ranging from 0.28% to 6%. [5] [7]

Non-IgE-mediated anaphylactoid reactions to protamine sulfate are more common than IgE-mediated anaphylaxis. [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. [5]

References

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External links