title: Aprotinin in fibrin tissue adhesives induces specific antibody response and increases antibody response of high-dose intravenous application.
abstract: BACKGROUND
  In cardiac operations, aprotinin therapy is used either locally as a component of commercially available fibrin tissue adhesives, intravenously, or combined. Our aim was to examine the formation of aprotinin-specific antibodies with regard to the application mode.
  
  
  METHODS
  Sera of 150 patients who had undergone cardiac operations and were receiving aprotinin therapy for the first time were sampled before the operation and at medians of 3.5 and 13.3 months after the operation. Aprotinin-specific IgG including all subgroups and aprotinin-specific IgE were analyzed. Aprotinin was given locally (as contained in fibrin sealant; n = 45; median dose, 6000 KIU), intravenously (n = 46; 2.000 x 10(6) KIU), and combined (n = 59; 2.012 x 10(6) KIU).
  
  
  RESULTS
  At 3.5 months, the prevalence of aprotinin-specific IgG antibodies was 33% (15/45 patients) after local, 28% (13/46 patients) after intravenous, and 69% (41/59 patients) after combined exposure (P =.0001). At 13.3 months, the prevalence of aprotinin-specific IgG antibodies was 10% (4/41 patients) after local, 31% (13/42 patients) after intravenous, and 49% (28/57 patients) after combined exposure. Total aprotinin dose was similar in patients who were antibody positive and negative. Before the operation, no aprotinin-specific antibodies were detected. Aprotinin-specific IgE were not found after the operation.
  
  
  CONCLUSIONS
  Local aprotinin contact induces a specific immune response and reinforces that of intravenous exposure. The antibody spectrum is identical to the immune response induced by intravenous exposure. Any exposure should be documented. For use in cardiac operations as a hemostyptic, the necessity itself and alternatives for aprotinin as a stabilizing agent merit consideration.
authors.affiliation: Department of Surgery, Division of Thoracic Surgery, Tübingen University Hospital, Germany.
authors.forename: A M
authors.initials: AM
authors.lastname: Scheule
authors.forename: W
authors.initials: W
authors.lastname: Beierlein
authors.forename: H P
authors.initials: HP
authors.lastname: Wendel
authors.forename: M J
authors.initials: MJ
authors.lastname: Jurmann
authors.forename: F S
authors.initials: FS
authors.lastname: Eckstein
authors.forename: G
authors.initials: G
authors.lastname: Ziemer
mesh_terms: D000917:Antibody Formation; D007611:Aprotinin / Q000276:immunology*; D006348:Cardiac Surgical Procedures; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D015718:Fibrin Tissue Adhesive / Q000008:administration & dosage / Q000627:therapeutic use*; D005455:Fluorescent Antibody Technique; D005500:Follow-Up Studies; D006331:Heart Diseases / Q000276:immunology / Q000601:surgery; D006490:Hemostatics / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007073:Immunoglobulin E / Q000032:analysis*; D007074:Immunoglobulin G / Q000032:analysis*; D007275:Injections, Intravenous; D007432:Intraoperative Period; D011446:Prospective Studies; D015842:Serine Proteinase Inhibitors / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D015718:Fibrin Tissue Adhesive; D006490:Hemostatics; D007074:Immunoglobulin G; D015842:Serine Proteinase Inhibitors; D007073:Immunoglobulin E; D007611:Aprotinin