title: Single doses of intravenous protamine result in the formation of protamine-specific IgE and IgG antibodies.
abstract: BACKGROUND
  Protamine reactions are a well-recognized and serious complication of intravenous protamine administration. IgE-mediated anaphylaxis occurs after initial sensitization and subsequent re-exposure to antigens. Subcutaneous protamine in insulin preparations is associated with protamine-specific IgE and IgG antibody production. In contrast, the influence of intravenous protamine administration on protamine-specific IgE and IgG antibody formation has never been investigated.
  
  
  METHODS
  Sera from 93 patients were analyzed for protamine-specific IgE and IgG antibodies both before and 4 to 6 weeks after exposure to single doses of intravenous protamine. Specific clinical variables were assessed by univariate and multivariate analyses to determine independent predictors of protamine-specific antibody production.
  
  
  RESULTS
  In patients who were previously seronegative, intravenous protamine administration resulted in protamine-specific IgE and IgG antibody production in 17 of 93 (18%) and 15 of 93 (16%) patients, respectively. As determined by multivariate analysis, male gender (p = 0.06) and insulin-dependent diabetes mellitus (p = 0.002) were associated with protamine-specific IgG but not IgE antibody production.
  
  
  CONCLUSIONS
  Single-dose intravenous protamine resulted in protamine-specific IgE and/or IgG antibody production in 26 of 93 (28%) of patients. Seroconversion was associated with male gender and insulin-dependent diabetes mellitus. Patients responding immunologically to protamine may be at increased risk for experiencing reactions on subsequent exposure.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21287-8711, USA.
authors.forename: D P
authors.initials: DP
authors.lastname: Nyhan
authors.forename: E L
authors.initials: EL
authors.lastname: Shampaine
authors.forename: C A
authors.initials: CA
authors.lastname: Hirshman
authors.forename: R G
authors.initials: RG
authors.lastname: Hamilton
authors.forename: S M
authors.initials: SM
authors.lastname: Frank
authors.forename: W A
authors.initials: WA
authors.lastname: Baumgartner
authors.forename: N F
authors.initials: NF
authors.lastname: Adkinson
mesh_terms: D000368:Aged; D000918:Antibody Specificity; D006348:Cardiac Surgical Procedures / Q000009:adverse effects; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007275:Injections, Intravenous; D007432:Intraoperative Period; D008297:Male; D015999:Multivariate Analysis; D011183:Postoperative Complications / Q000276:immunology; D011479:Protamines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology*
chemical_list: D007074:Immunoglobulin G; D011479:Protamines; D007073:Immunoglobulin E