title: Modern management of non-chemotherapy drug-induced agranulocytosis: a monocentric cohort study of 90 cases and review of the literature.
abstract: BACKGROUND: The present study reports a monocentric experience of 90 drug-induced agranulocytosis cases and discusses their management, in particular the role of hematopoietic growth factors. METHODS: Data from 90 patients with drug-induced agranulocytosis who met the criteria of the IAAAS group and of Bénichou and Solal-Celigny [Nouv Rev Fr Hematol 1993; 33: 257.] were retrospectively reviewed. All cases were extracted from a cohort study of the Hopitaux Universitaires de Strasbourg, France. Data were specifically analyzed with regard to the use of hematopoietic growth factors (in 42 patients). RESULTS: Mean patient age was 63 (range 17-95) years and the sex ratio (M/F) was 0.39. An underlying disease was present in 37% of the patients. Antibiotics (25%), antithyroid drugs (23%), and antiaggregative platelet agents (16%) were the most frequent causative drugs. Main clinical features included isolated fever (41%), septicemia or septic shock (31%), and pneumonia (10%). Mean neutrophil count was 0.13 (range 0-0.46)x10(9)/l. Outcome was favorable in 98% of patients. The mean durations of hematological recovery (neutrophil count over 1.5x10(9)/l), antibiotic therapy, and hospitalization was 8.5 (range 2-21) days, 9.2 (range 2-21) days, and 10.5 (range 3-23) days, respectively. All patients were treated with broad-spectrum antibiotics and 42 patients with hematopoietic growth factors. In these 42 patients, the mean durations for hematological recovery, antibiotic therapy, and hospitalization were significantly reduced at: 6.3 (range 2-16) days, 7.1 (range 2-16) days, and 9.1 (range 3-23) days, respectively (all P<0.05). CONCLUSIONS: The present study shows that new causative drugs are emerging (antibiotics, antithyroid, and antiaggregative platelet agents), that drug-induced agranulocytosis remains typically a serious accident with severe sepsis, and that modern management with broad spectrum antibiotics and hematopoietic growth factors may reduce the mortality.
authors.affiliation: Department of Internal Medicine, Service de Médecine Interne, Clinique Médicale B, Hôpitaux Universitaires de Strasbourg, 1 Place de l'Hôpital, 67 091 Cedex, Strasbourg, France
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Andrès
authors.forename: Frédéric
authors.initials: F
authors.lastname: Maloisel
authors.forename: Jean Emmanuel
authors.initials: JE
authors.lastname: Kurtz
authors.forename: Georges
authors.initials: G
authors.lastname: Kaltenbach
authors.forename: Martine
authors.initials: M
authors.lastname: Alt
authors.forename: Jean Christophe
authors.initials: JC
authors.lastname: Weber
authors.forename: Jean
authors.initials: J
authors.lastname: Sibilia
authors.forename: Jean Louis
authors.initials: JL
authors.lastname: Schlienger
authors.forename: Jean Frédéric
authors.initials: JF
authors.lastname: Blicklé
authors.forename: Jean Marie
authors.initials: JM
authors.lastname: Brogard
authors.forename: Patrick
authors.initials: P
authors.lastname: Dufour