Experimental drug-induced immune thrombocytopenia in monkeys.
In these studies we report the induction, by 7,8-dimethoxy-1H-3-benzaepin-2-amine HCl, of immune thrombocytopenia in monkeys and its characterization by flow cytometry. Three of eight monkeys developed thrombocytopenia following administration of high doses (35 mg/kg) of the drug. The characteristics of the thrombocytopenia, including rapid induction on rechallenge with the drug, met the criteria indicative of drug-induced immune thrombocytopenia. Platelet surface-associated immunoglobulin could be detected by flow cytometry as early as 21 days before the onset of thrombocytopenia. A critical concentration of antibody on the platelet surface appeared to be necessary for elimination of the platelets from the blood. Evidence from experiments using the serum from an affected monkey suggested that drug interaction with the platelet surface produced a site for antibody binding, possibly a neoantigen, which required the continued presence of the drug.
Petersen
B H
BH
Lilly Laboratory for Clinical Research, Eli Lilly and Company, Indianapolis, Indiana.
Heim
M C
MC
White
J F
JF
D000818:Animals; D001552:Benzazepines / Q000633:toxicity*; D001792:Blood Platelets / Q000276:immunology; D001853:Bone Marrow / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D008251:Macaca; D008253:Macaca mulatta; D008297:Male; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000473:pathology
D001552:Benzazepines; C044128:7,8-dimethoxy-1H-3-benzazepin-2-amine hydrochloride