Idiosyncratic drug-induced agranulocytosis: 7 year-analysis in a French university hospital

• Published in: Annales pharmaceutiques françaises Vol. 78; no. 3; p. 230
• Main Authors: Duwez, M, Szymanski, G, Carre, M, Mallaret, M, Lepelley, M
• Format: Journal Article
• Language: French
• Published: France 01-05-2020
• Subjects: Adult; Aged; Aged, 80 and over; Agranulocytosis - chemically induced; Agranulocytosis - epidemiology; Blood Cell Count; Bone Marrow - pathology; Drug-Related Side Effects and Adverse Reactions - epidemiology; Female; France - epidemiology; Hospitals, University; Humans; Male; Middle Aged; Myelography; Pharmacovigilance; Retrospective Studies; Young Adult; France; Drugs; Physiopathologie; Médicaments; Drug side effect; Agranulocytosis; Effet indésirable médicamenteux; Agranulocytoses; Pharmacovigilance; Physiopathology
• ISSN: 0003-4509
• DOI: 10.1016/j.pharma.2020.02.004

Idiosyncratic drug-induced agranulocytosis is a rare but potentially serious haematological disorder. The pathophysiological mechanisms are complex and poorly understood. We aimed at investigating agranulocytosis drug related causes from the myelograms with "myeloid maturation arrest" performed in our university hospital over the last seven years.
A retrospective analysis of myelograms collected for agranulocytosis was performed from 1st January 2010 to 31th December 2016. We used the method of Bégaud et al. for drug causality assessment.
Among the 104 myelograms analysed, 41 agranulocytosis were drug-induced, whose 28 were idiosyncratic. Among these 28 cases, 26 different drugs were involved. Agranulocytosis was a known adverse reaction in the summary of the product characteristics for 24 drugs, mainly associated with undetermined frequency (n=7). Mean onset latency was 38.1 days after starting the drug (calculated for n=23 cases) and granulocyte growth factors were used in 50% of cases without shortening the mean delay of blood count recovery. Bone marrow presented hypereosinophilia in 29% of cases. Pharmacovigilance reporting rate was 48%.
A "maturation arrest" in the myelogram is not pathognomonic for idiosyncratic drug-induced agranulocytosis. This rare event require multidisciplinary care involving haematologists, biologists and pharmacovigilance experts. Agranulocytosis reporting rate was high compared with usual adverse drug reaction reporting rate (5 to 10%), probably related to the potential severity of this event.