Modern management of non-chemotherapy drug-induced agranulocytosis: a monocentric cohort study of 90 cases and review of the literature

• Published in: European journal of internal medicine Vol. 13; no. 5; pp. 324 - 328
• Main Authors: Andrès, Emmanuel, Maloisel, Frédéric, Kurtz, Jean-Emmanuel, Kaltenbach, Georges, Alt, Martine, Weber, Jean-Christophe, Sibilia, Jean, Schlienger, Jean-Louis, Blicklé, Jean-Frédéric, Brogard, Jean-Marie, Dufour, Patrick
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-08-2002; Elsevier
• Subjects: Antibiotics; Drug-induced agranulocytosis; Fever; G-CSF; Human health and pathology; Infections; Life Sciences; Sepsis syndrome; Sepsis syndrome; Drug-induced agranulocytosis; Infections; Antibiotics; G-CSF; Fever
• ISSN: 0953-6205; 1879-0828
• DOI: 10.1016/S0953-6205(02)00085-7

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)×10
9/l. Outcome was favorable in 98% of patients. The mean durations of hematological recovery (neutrophil count over 1.5×10
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.