Affiliation:
1. Abbott GmbH & Co. KG, Preclinical Safety, Ludwigshafen, Germany
2. Abbott Laboratories, Preclinical Safety, Abbott Park, Illinois, USA
Abstract
During baseline evaluation prior to a preclinical safety study, a 10-month-old male pure-bred Beagle dog was found to have marked thrombocytopenia (6 × 103 platelets [PLT]/µL) associated with a mean platelet volume (MPV) of 17.9 fL. Tests for Rickettsia rickettsii, Ehrlichia canis, and Borrelia burgdorferi were negative. Buccal bleeding time was normal. Over 3 months, PLT were 4 to 141 × 103 PLT/µL, and MPV was 11.4 to 25.1 fL; however, PLT were <50 × 103 PLT/µL and MPV was >16 fL during most of this period. Antinuclear antibody (ANA) and anti-PLT antibody tests were negative. Genotyping for the presence of a beta 1-tubulin mutation demonstrated the normal wild-type gene. Treatment with prednisone resulted in normal values after only 3 days. Ultrastructure of enlarged PLT was consistent with that of immature PLT, characterized by reduced numbers of peripheral microtubules and the presence of rough endoplasmic reticulum, free ribosomes, Golgi apparatus, and a prominent canalicular system. PLT ultrastructure and glucocorticoid responsiveness supported a diagnosis of immune-mediated thrombocytopenia that was masked by the cyclic nature of PLT decreases and lack of clinical signs. Inclusion of such a dog in a preclinical safety study could result in misinterpretation of clinical pathology findings.
Subject
Cell Biology,Toxicology,Molecular Biology,Pathology and Forensic Medicine
Cited by
4 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献