Protamine sulfate


Protamine sulfate is a medication that is used to reverse the effects of heparin. It is specifically used in heparin overdose, in low molecular weight heparin overdose, and to reverse the effects of heparin during delivery and heart surgery. It is given by injection into a vein. The onset of effects is typically within five minutes.
Common side effects include low blood pressure, slow heart rate, allergic reactions, and vomiting. Allergic reactions may be severe and include anaphylaxis. The risk is greater in males who have had a vasectomy. While there is no evidence of harm from using during pregnancy it has not been well studied in this group. Protamine works by binding with heparin.
Protamine sulfate was approved for medical use in the United States in 1969. It is on the World Health Organization's List of Essential Medicines. It was originally made from the sperm of salmon. It is now mainly made using recombinant biotechnology.

Medical uses

Protamine sulfate is usually administered to reverse the large dose of heparin administered during certain surgeries, especially heart surgery where anti-coagulation is necessary to prevent clot formation within the cardiopulmonary bypass pump apparatus. A dose of protamine is given once 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 and nonviral-mediated delivery mechanisms.
Protamine is used in insulin aspart protamine and NPH insulin.

Dosage

Dosage for heparin reversal is 1.0 to 1.5 mg protamine sulfate IV for every 100 IU of active heparin. PTT should be monitored at 5 to 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. 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 and steroids may minimize these reactions. A 5 to 10 mg test dose is recommended following pretreatment before administering the full dose.

Mechanism

It is a highly cationic peptide that binds to either heparin or low molecular weight heparin 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.

History

was originally isolated from the sperm of salmon, but is now mostly made by recombinant biotechnology.