TY - JOUR
T1 - Anti-platelet antibodies in a natural animal model of sulphonamide- associated thrombocytopaenia
AU - Lavergne, Sidonie N.
AU - Trepanier, Lauren A.
N1 - Funding Information:
This study was funded by a grant from the US National Institutes of Health, GM 61753. The authors would like to thank Dr Daniel Bougie (Blood Center of Wisconsin, Milwaukee, WI) for providing mouse anti-human platelet GP, purified human GP IIb/IIIa complex, and technical advice. The authors would also like to thank Dr David Wilcox (Medical College of Wisconsin, Milwaukee, WI), for providing blood from a dog with Glanzmann’s thrombasthenia, and Dr Kraig Abrams (Puget Sound Blood Center, Seattle, WA) and Dr Douglas Weiss (University of Minnesota) for the gift of sera from dogs with antibody-mediated thrombocytopaenia. We also would like to thank the owners of canine platelet donors and negative control dogs used in this study.
Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2007/12
Y1 - 2007/12
N2 - Delayed hypersensitivity (HS) reactions to sulphonamide antimicrobials occur in both humans and dogs with a similar clinical presentation, and may include thrombocytopaenia. Drug-dependent anti-platelet antibodies have been identified in humans with sulphonamide-associated thrombocytopaenia. Our purpose was to determine whether similar antibodies were present in dogs with sulphonamide-associated thrombocytopaenia. Flow cytometry was used to detect anti-platelet antibodies in sera from 32 dogs with sulphonamide HS, eight dogs that tolerated sulphonamide therapy without adverse reactions and nine healthy control dogs were used as controls. Anti-platelet antibodies were found more frequently, with significantly stronger fluorescence signals, in HS dogs (75%) compared to 'tolerant' dogs (38%), and in HS dogs with thrombocytopaenia (90%) compared to HS dogs with normal platelet counts (46%). Binding to platelets was enhanced in the presence of soluble sulphonamide in 42% of positive samples. Experiments with canine Glanzmann's platelets, and competition assays with fibrinogen fragments or anti-GP antibodies, did not support the hypothesis that these canine antibodies target the fibrinogen receptor. In conclusion, anti-platelet antibodies were identified in dogs with sulphonamide-associated thrombocytopaenia, which suggests a similar immunopathogenesis for this reaction in dogs as seen in humans. Further work in both species will determine whether these antibodies are pathogenic in vitro.
AB - Delayed hypersensitivity (HS) reactions to sulphonamide antimicrobials occur in both humans and dogs with a similar clinical presentation, and may include thrombocytopaenia. Drug-dependent anti-platelet antibodies have been identified in humans with sulphonamide-associated thrombocytopaenia. Our purpose was to determine whether similar antibodies were present in dogs with sulphonamide-associated thrombocytopaenia. Flow cytometry was used to detect anti-platelet antibodies in sera from 32 dogs with sulphonamide HS, eight dogs that tolerated sulphonamide therapy without adverse reactions and nine healthy control dogs were used as controls. Anti-platelet antibodies were found more frequently, with significantly stronger fluorescence signals, in HS dogs (75%) compared to 'tolerant' dogs (38%), and in HS dogs with thrombocytopaenia (90%) compared to HS dogs with normal platelet counts (46%). Binding to platelets was enhanced in the presence of soluble sulphonamide in 42% of positive samples. Experiments with canine Glanzmann's platelets, and competition assays with fibrinogen fragments or anti-GP antibodies, did not support the hypothesis that these canine antibodies target the fibrinogen receptor. In conclusion, anti-platelet antibodies were identified in dogs with sulphonamide-associated thrombocytopaenia, which suggests a similar immunopathogenesis for this reaction in dogs as seen in humans. Further work in both species will determine whether these antibodies are pathogenic in vitro.
KW - Dog
KW - Drug hypersensitivity
KW - Sulphadiazine
KW - Sulphamethoxazole
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U2 - 10.1080/09537100701392913
DO - 10.1080/09537100701392913
M3 - Article
C2 - 18041651
AN - SCOPUS:36549043931
SN - 0953-7104
VL - 18
SP - 595
EP - 604
JO - Platelets
JF - Platelets
IS - 8
ER -