VOL. 2, No. 3, July 2005

E. Andrès, et al. [2005] Med Hypotheses Res 2: 515-524.

The Etiology, Epidemiology and Management of
Idiosyncratic Drug-Induced Agranulocytosis

Emmanuel Andrès*, Stéphane Affenberger, Martine Alt, Georges
Kaltenbach and Frédéric Maloisel

Departments of Internal Medicine (E.A., S.A.), Internal Medicine and Geriatrics (G. K.) and
Onco-Hematology (F.M.), University Hospital of Strasbourg, France, and
Pharmacovigilance Center of Alsace, France (M.A.)

Abstract. Objective: To review the literature concerning idiosyncratic drug-induced
agranulocytosis, a rare but life-threatening potential adverse event of most drugs. Data
sources: Articles were identified through searches of Medline (January 1966 to March 2005).
Unpublished data from our cohort of drug-induced agranulocytosis in the University
Hospital of Strasbourg, France were also considered. Data extraction and synthesis: All of
the papers and abstracts were reviewed by at least two senior researchers that selected the
data used in the study. The incidence of idiosyncratic drug-induced agranulocytosis remains
stable in the past twenty years: 2.4 to 15.4 cases per million, despite the emergence of new
causative drugs, mainly antibiotics, antiplatelet agents and antithyroid drugs. To date, drug-
induced agranulocytosis remains a serious adverse event due to the frequency of severe
sepsis with severe deep infections (as pneumonia), septicemia and septic shock in around 2/3
of patients. In this setting, old age (>65 years), septicemia or shock, metabolic disorders
such as renal failure, and a neutrophil count <0.1 x 10[9]/L are poor prognostic factors.
Nevertheless with appropriate management using pre-established procedures, with
intravenous broad-spectrum antibiotic therapy and hematopoietic growth factors, the
mortality rate is currently around 5%. Conclusions: Given the increased life expectancy and
subsequent longer exposure to drugs, as well as the development of new agents, health care
professionals should be aware of this adverse event and its management.

*Address all correspondence to: Dr. E. Andrès, Service de Médecine Interne, Clinique
Médicale B, Hôpitaux Universitaires de Strasbourg, 1 Porte de l’Hôpital, 67 091 Strasbourg
Cedex, France.
Phone: 33-3-88-11-50-66. Fax: 33-3-88-11-62-62. E-Mail:

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