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Cephalosporin‐induced immune cytopenia in the dog: Demonstration of erythrocyte‐, neutrophil‐, and platelet‐associated igg following treatment with cefazedone
Author(s) -
Bloom John C.,
Thiem Patricia A.,
Sellers Teresa S.,
Lewis Hugh B.,
Deldar Ahmed
Publication year - 1988
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.2830280202
Subject(s) - medicine , neutropenia , cytopenia , immunology , cephalosporin , antibody , hemolytic anemia , leukopenia , anemia , coombs test , immune system , gastroenterology , bone marrow , toxicity , antibiotics , biology , microbiology and biotechnology
Cephalosporin treatment in man has been associated with a low incidence of hemolytic anemia, thrombocytopenia, and neutropenia; some cases have been shown to be immune‐mediated. This triad of blood dyscrasias was also demonstrated in our laboratory in a series of toxicity studies in dogs of two cephalosporin compounds, cefonicid and cefazedone; these studies provided evidence for drug‐associated immune hemolytic anemia, based on conventional laboratory tests. To further investigate possible immune mechanisms of the cephalosporin‐induced cytopenias, we measured erythrocyte‐associated, platelet‐associated (PAIgG), and serum antineutrophil IgG over the course of cephalosporin treatment, using highly sensitive 125 I‐staphylococcal protein A (SPA) assays, as well as the direct antiglobulin test; we compared these findings with the hematologic changes. Intravenous treatment with high doses of cefazedone (540 mg/ kg/day, increased to a maximum of 840 mg/kg/day for 4 months or until hematologic effects were evident) resulted in a high incidence of anemia (7/14), thrombocytopenia (11/14), and neutropenia (7/14). Of the affected dogs examined, 6/7 with anemia, 9/9 with thrombocytopenia, and 7/7 with neutropenia showed increased levels of the respective cell‐associated antibody, compared with untreated controls. Unaffected dosed animals generally did not show these changes. In 3/3 dogs examined following remission of thrombocytopenia, PAIgG returned to levels comparable with controls; as one of these dogs suffered a relapse, increased PAIgG was again observed. Animals sacrificed during cytopenic episodes showed cytologic and histologic evidence of increased hemophagocytosis. We conclude that antibody‐mediated blood cell destruction contributes to all three cephalosporin‐induced cytopenias in the dog.