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Ann Thorac Surg 2000;69:1298
© 2000 The Society of Thoracic Surgeons

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CORRESPONDENCE

Anaphylactic aprotinin reaction

^a Division of Thoracic, Cardiac and Vascular Surgery, Eberhard-Karls-University Tübingen, Hoppe-Seyler-Str 3, D-72076 Tübingen, Germany

To the Editor

We refer to the article by Cohen and colleagues [1] presenting the unusual case of a 3.5-year-old boy with a near-fatal reaction to a test dose of aprotinin administered intravenously before complete surgical repair of tetralogy of Fallot. The boy survived thanks to resuscitation using cardiopulmonary bypass support. An enzyme-linked immunosorbent assay (ELISA) revealed aprotinin-specific IgE. Former contacts or cross-sensitizations seemed to be disclosed.

We congratulate the authors for managing this near-fatal situation and saving the boy’s life, but question some details of the case. The history as presented does not disclose previous aprotinin contacts. However, formation of aprotinin-specific IgE is very improbable without former antigen contacts. As intravenous contacts and cross-sensitizations are ruled out, hidden local contacts by fibrin tissue adhesives have to be considered. Most commercially available fibrin sealants contain small doses of aprotinin which can induce temporarily detectable levels of specific IgE as we have observed in a study of 49 children [2]. Even self-made fibrin glues may contain aprotinin [3]. Repeated local contacts can also cause generalized allergic reactions [4]. In the present case report we miss a statement on the possibility of former local aprotinin contacts although it had not been documented.

The formation of allergen-specific antibodies is a time-dependent dynamic process. Antibody screening tests must be interpreted with regard to the time lapse between the last allergen contact and the time of antibody screening. Concerning aprotinin, we have made some observations, which could contribute to the discussion of the present case. Aprotinin-specific IgE may become detectable 1 week after primary aprotinin contact [2]. Consequently, only positive IgE tests dating from before or immediately after the reaction indicate preexistent sensitization. If the highly positive IgE test in this boy dates from later than a few days after the reaction, it can also be due to the primary immune response to the test dose. Then the adverse reaction would not have been IgE mediated and thus not anaphylactic. However, this consideration does not rule out aprotinin from being the causative agent, because there is still the possibility of an antibody-independent anaphylactoid reaction. For precise assessment of the actual mechanism of the case presented, the authors need to report the exact time lapse between the incriminated aprotinin administration and the time of IgE testing thereafter.

According to our experience, it is extremely difficult to obtain reproducible ELISA results for aprotinin-specific IgE as the authors did. This is due to the extremely low amount of specific serum IgE. Therefore we rely on a fluorescence enzyme immunoassay, which is more sensitive for allergen-specific IgE.

We do agree with Cohen and colleagues that the possibility of an allergic reaction should be considered whenever aprotinin is used. But we have doubts concerning the interpretation of the present case as an anaphylactic reaction due to a primary exposure.

References

1. Cohen D.M., Norberto J., Cartabuke R., Ryu G. Severe anaphylactic reaction after primary exposure to aprotinin. Ann Thorac Surg 1999;67:837-838.[Abstract/Free Full Text]
2. Scheule A.M., Beierlein W., Wendel H.P., Eckstein F.S., Heinemann M.K., Ziemer G. Fibrin sealant, aprotinin, and immune response in children undergoing operations for congenital heart disease. J Thorac Cardiovasc Surg 1998;115:883-889.[Abstract/Free Full Text]
3. Spotnitz W.D. Fibrin sealant in the United States. Thromb Haemost 1995;74:482-485.[Medline]
4. Beierlein W, Scheule AM, Antoniadis G, Braun C, Schosser R. An immediate allergic skin reaction to aprotinin after reexposure to fibrin sealant. Transfusion (in press).

This article has been cited by other articles:

				L. F. L. Almodovar, P. Lima, A. Canas, and M. Calleja Fatal anaphylactoid reaction after primary exposure to aprotinin Interactive CardioVascular and Thoracic Surgery, February 1, 2006; 5(1): 25 - 26. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Albertus M. Scheule Gerhard Ziemer Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Beierlein, W. Articles by Ziemer, G. Search for Related Content PubMed Articles by Beierlein, W. Articles by Ziemer, G.