9012-00-4

Water soluble, producing basic solu- tions.

Protamine from salmon has been used to avoid in vitro AT complex formation in samples from dogs pre-treated with heparin. It has also been used to study the influences of external potential on adsorption of various proteins to a metal surface.

Protamines are proteins rich in cysteine and arginine. It possesses many phosphorylation sites. Salmon fish contains around 15 genes encoding protamine. It is found to be localized to the sperm head.

Protamines are found to displace histones in DNA during spermatogenesis in animals and plants. Protamine is useful as a heparin neutralizer during heart surgery, dialysis and in many other clinical procedures.

Protamine sulfate has been approved in the United States as a specific antagonist to heparin since 1968. Protamines are an arginine-rich, highly basic group of simple proteins derived from salmon sperm. The highly acidic heparin polysaccharides exhibit their anticoagulant activity through binding to antithrombin III. Because of the basicity of protamine, heparin has an increased affinity for protamine relative to antithrombin III. In fact, its binding affinity for protamine is so much greater than that of antithrombin III that protamine actually will induce dissociation of the heparin/antithrombin III complex. If protamine is administered in the absence of heparin, it can have marked effects on coagulation. Protamine is not completely selective for heparin and, in vivo, also interacts with fibrinogen, platelets, and other plasma proteins causing anticoagulation. For this reason, use of the minimal amount of protamine necessary to antagonize heparin-associated bleeding should be employed (usually 1 mg of protamine intravenously for every 100 U of heparin remaining in the patient).

Anaphylaxis also has been associated with the use of protamine. Although development of protamine anaphylaxis is not limited to diabetics, those patients with diabetes that have used protaminecontaining insulin (NPH or protamine zinc) do have a slightly increased risk of anaphylaxis. Some less common reactions to protamine include pulmonary vasoconstriction, hypotension, and thrombus formation.