title: Clinical experience of clozapine-induced neutropenia in the UK. Laboratory investigation using liquid culture systems and immunofluorocytometry.
abstract: An incidence of drug-induced neutropenia of 2.5% has been found in the first 1000 patients to be treated with clozapine in the UK. The majority of affected patients experienced mild neutropenia (n = 22) with only 3 patients developing agranulocytosis. Data collected from these 25 patients suggest that the mechanism of neutropenia may be multifactorial. Laboratory investigation using liquid culture systems and immunofluorocytometry has identified clozapine and its major metabolite N-desmethyl clozapine as exhibiting toxic effects against myeloid maturation and myeloid mitotic compartments, respectively. Increased susceptibility to the toxic effects of clozapine was shown in 1 patient who had previously developed clozapine-associated neutropenia. No clinical or laboratory evidence of drug-induced antineutrophil or antimyeloid precursor antibodies was found.
authors.affiliation: Department of Haematology, Royal Free Hospital School of Medicine, London, England.
authors.forename: P A
authors.initials: PA
authors.lastname: Veys
authors.forename: S
authors.initials: S
authors.lastname: Wilkes
authors.forename: S
authors.initials: S
authors.lastname: Shah
authors.forename: R
authors.initials: R
authors.lastname: Noyelle
authors.forename: A V
authors.initials: AV
authors.lastname: Hoffbrand
mesh_terms: D001853:Bone Marrow / Q000187:drug effects / Q000276:immunology; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D003024:Clozapine / Q000009:adverse effects*; D005455:Fluorescent Antibody Technique; D006801:Humans; D007070:Immunoglobulin A / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D015994:Incidence; D008938:Mitosis / Q000187:drug effects; D009503:Neutropenia / Q000139:chemically induced* / Q000453:epidemiology / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D012189:Retrospective Studies; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D007070:Immunoglobulin A; D007075:Immunoglobulin M; D003024:Clozapine