title: Unexpected death: anaphylactic intraoperative death due to Thymoglobulin carbohydrate excipient.
abstract: Anaphylactic shock is a life-threatening allergic response characterized by severe hypotension, inducing tissue hypoperfusion with possible multi-organ failure and death. We describe the first case of fatal intra-operative anaphylactic shock due to prolonged infusion of Thymoglobulin during Orthotopic Liver Transplantation (OLT), resulting from recruitment of both mastocytes and basophils, activated and degranulated. Post-mortem serological analysis on a preserved, pre-OLT sample of the patient's blood revealed specific IgE against carbohydrate cross-reactive determinants (CCDs), such as MUXF3 and nAna c2, proving that anaphylactic reaction was triggered by the Thymoglobulin carbohydrate excipient (sugar alcohol mannitol), rather than anti-thymocyte globulin itself. Our findings are consistent with scientific data reported in the literature, where only one case of non-fatal anaphylaxis to Thymoglobulin has been described, despite the existence of proven cases of anaphylactic reaction to mannitol. This case highlights the need to pay particular attention in future not only to active substances but also to drug excipients, above all during intra-operative drug delivery. In view of the important role played by basophils in this kind of anaphylaxis, the basophil activation test (BAT) could prove useful in preventing anaphylactic death from CCDs.
authors.affiliation: Department of Diagnostic Services, Pathology and Legal Medicine, Section of Pathology, University of Modena and Reggio Emilia, Modena, Italy. emailmedical@gmail.com
authors.forename: Luca
authors.initials: L
authors.lastname: Roncati
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Barbolini
authors.forename: Alda Tiziana
authors.initials: AT
authors.lastname: Scacchetti
authors.forename: Stefano
authors.initials: S
authors.lastname: Busani
authors.forename: Antonio
authors.initials: A
authors.lastname: Maiorana
mesh_terms: D000707:Anaphylaxis / Q000139:chemically induced*; D000961:Antilymphocyte Serum / Q000008:administration & dosage / Q000009:adverse effects*; D001491:Basophils / Q000378:metabolism; D001963:Bromelains / Q000276:immunology; D002241:Carbohydrates / Q000276:immunology*; D003429:Cross Reactions; D049429:Forensic Pathology; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D007431:Intraoperative Complications; D008099:Liver / Q000166:cytology; D016031:Liver Transplantation; D008297:Male; D008407:Mast Cells / Q000378:metabolism; D008875:Middle Aged; D013154:Spleen / Q000166:cytology; D053802:Tryptases / Q000097:blood
chemical_list: D000961:Antilymphocyte Serum; D002241:Carbohydrates; D007166:Immunosuppressive Agents; D007073:Immunoglobulin E; D001963:Bromelains; C512542:thymoglobulin; D053802:Tryptases