Routine intraoperative application of high-dose aprotinin in open heart surgery in adults: Antibody formation after first exposure

Abstract

High-dose aprotinin is now routinely used in cardiac surgery to reduce postoperative blood loss and transfusion requirements, although several cases of anaphylactic reactions to the proteinase inhibitor have been reported. As part of a multi-centre study to evaluate the immunological response to aprotinin after first exposure 61 cardiac surgical patients were treated with the Hammersmith regimen. Patients with previous aprotinin exposure were excluded from the study. To determine specific IgG and IgE antibodies blood samples were taken pre-operatively, within 3 to 4 weeks and 6 to 7 months after operation. Determinations were made by using Western Blot and ELISA methods. Fifty-six patients were followed up for a 6-month period, 26 (46.4%) of them developed IgG antibodies to aprotinin determined by Western Blot, whereas only 14 (26.8%) patients with IgG antibodies were found by the ELISA. IgE antibodies were not found in any of the patients. On hospital admission and 6 months post-operatively additional intradermal prick tests were performed. No clear-cut positive reaction to the skin test was found in any patient.

Aprotinin in fibrin tissue adhesives induces specific antibody response and increases antibody response of high-dose intravenous application

“…5,19,20 Former studies have revealed a prevalence of specific antibodies in about 50% of patients who had received 1 intravenous high dose of aprotinin. 21,22 In cardiac operations, aprotinin is used either locally as a component of commercially available fibrin tissue adhesives, intravenously, or in combination of both. Therefore it was our aim to examine whether the immunostimulatory potency of a first-time contact depends on the route of administration.…”

Prevalence of anaphylactic reactions to aprotinin: Analysis of two hundred forty-eight reexposures to aprotinin in heart operations

“…7-15 It has been shown that formation of immunoglobulin (Ig) G antibodies to aprotinin takes place in about 50% of all patients treated with aprotinin. 16,17 Because aprotinin has been used on a broad scale in Europe during the past 8 years in many cardiac centers, the number of patients scheduled for a second cardiac operation after a primary exposure to aprotinin is increasing. Aprotinin is especially efficacious in cardiac reoperations 1 ' 18; however, the question remains whether the relative risk of an anaphylactic reaction might outweigh the benefit of this drug if it is given to previously sensitized patients.…”

Antifibrinolytic drugs and perioperative hemostasis

“…As with the report by Cosgrove et al [43], failure to provide adequate intraoperative anticoagulation in the presence of aprotinin would appear to be the most likely explanation for these complications. As many as 50% of patients receiving high-dose aprotinin develop specific IgG antibodies within 3 months of exposure, and over half of these patients continue to test positive for the antibody 4 years following the initial exposure [51,52]. One final concern relates to the potential for anaphylactoid reactions following aprotinin.…”

“…As a naturally occurring protein, aprotinin induces an immunologic response following administration. As many as 50% of patients receiving high-dose aprotinin develop specific IgG antibodies within 3 months of exposure, and over half of these patients continue to test positive for the antibody 4 years following the initial exposure [51,52]. Diefenbach et al [53] recently reported a fatal episode of anaphylactic shock following reexposure to aprotinin.…”