[2] Common side effects include low blood pressure, slow heart rate, allergic reactions, and vomiting.

A dose of protamine is given, by drip administered over several minutes, once the patient is off-pump, when extracorporeal circulation and anticoagulation are no longer needed.

In gene therapy, protamine sulfate has been studied as a means to increase transduction rates by both viral and nonviral-mediated delivery mechanisms (e.g. utilizing cationic liposomes).

[12][13][14] 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 Swiss medical student, Friedrich Miescher (1844-1895) became ill with typhoid fever complicated with partial deafness.

While Friedrich was analyzing the composition of salmon sperm, he isolated for the first time the alkaline substance of “protamine” nucleic acid in 1869 and he called it “nuclein”.

The protamine of salmon, later named “salmine”, which can be extracted with hydrochloric acid and precipitated with platinum chloride, corresponds to about 26.8 % of the dried sperm.

[19][20] Protamine sulfate replaced hexadimethrine bromide (Polybrene), another cationic agent that was the original heparin reversal agent in the early days of heart surgery, until studies in the 1960s suggested that hexadimethrine bromide might cause kidney failure when used in doses in excess of its therapeutic range.