title: Serious adverse reactions to protamine sulfate: are alternatives needed?
abstract: Protamine sulfate is a strongly cationic polypeptide that is used commonly in clinical medicine. It is administered regularly after cardiac catheterization, cardiothoracic and vascular surgical procedures, and less frequently after dialysis and leukapheresis because of its capacity to reverse the anticoagulant activity of heparin. In addition, because it delays the absorption of insulin, protamine is combined with insulin in protamine zinc insulin and neutral protamine Hagedorn insulin. Recently, there have been reports of adverse reactions to protamine (Table I). Although most of these reactions were relatively mild, three were fatal; one was clearly the result of type I anaphylaxis. Reactions occur predominantly in patients who were previously exposed to protamine through protamine-containing insulins or during heparin neutralization. Almost 50% of these patients were diabetic; most of whom received neutral protamine Hagedorn insulin, thereby enhancing their chance for presensitization. In 1983 we encountered three patients who suffered adverse reactions to protamine sulfate. Two of these patients will be presented here; the third patient, who died of IgE-mediated anaphylaxis, has already been reported and therefore is mentioned only briefly. We shall discuss adverse reactions to protamine sulfate and alternatives to the routine use of this drug.
authors.forename: J M
authors.initials: JM
authors.lastname: Weiler
authors.forename: P
authors.initials: P
authors.lastname: Freiman
authors.forename: M D
authors.initials: MD
authors.lastname: Sharath
authors.forename: W J
authors.initials: WJ
authors.lastname: Metzger
authors.forename: J M
authors.initials: JM
authors.lastname: Smith
authors.forename: H B
authors.initials: HB
authors.lastname: Richerson
authors.forename: Z K
authors.initials: ZK
authors.lastname: Ballas
authors.forename: P C
authors.initials: PC
authors.lastname: Halverson
authors.forename: D J
authors.initials: DJ
authors.lastname: Shulan
authors.forename: S
authors.initials: S
authors.lastname: Matsuo
mesh_terms: D000368:Aged; D000707:Anaphylaxis / Q000139:chemically induced; D002319:Cardiovascular System / Q000187:drug effects; D003167:Complement Activation / Q000187:drug effects; D004198:Disease Susceptibility; D005260:Female; D006494:Heparin Antagonists / Q000627:therapeutic use; D006634:Histamine H1 Antagonists / Q000627:therapeutic use; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000139:chemically induced; D007022:Hypotension / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D011479:Protamines / Q000009:adverse effects*; D012137:Respiratory System / Q000187:drug effects; D012871:Skin Diseases / Q000139:chemically induced; D013256:Steroids / Q000627:therapeutic use
chemical_list: D006494:Heparin Antagonists; D006634:Histamine H1 Antagonists; D011479:Protamines; D013256:Steroids