Article
Non-chemotherapy drug-induced agranulocytosis: a systematic review of case reports
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Authors
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Frank Andersohn
- Bremer Institut für Präventionsforschung und Sozialmedizin (BIPS), Bremen
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Christine Konzen
- Institut für klinische Pharmakologie, Charité - Universitätsmedizin Berlin, Berlin
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Edeltraut Garbe
- Bremer Institut für Präventionsforschung und Sozialmedizin (BIPS), Bremen
| Published: | September 6, 2007 |
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Outline
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Background: Non-chemotherapy drug-induced agranulocytosis is a rare adverse drug reaction characterized by a decrease in peripheral neutrophil count to <500/µl due to immunological or cytotoxic mechanisms. Discontinuation of the causative drug is crucial to avoid continuation of hazardous drug exposure, but its identification may be a challenging problem in patients with poly-pharmacotherapy.
Objectives: To identify drugs definitely or probably related to agranulocytosis in published case reports and series. To analyze these case reports with respect to several clinical characteristics.
Methods: We performed a systematic review of English-language and German-language case reports found in MEDLINE (1966-2006) or EMBASE (1989-2006) or in bibliographies of retrieved articles. We abstracted details about cases and assessed causality between drug intake and agranulocytosis using World Health Organization causality assessment criteria.
Results: Causality assessments of 980 reported cases of agranulocytosis were: definite 56 (6%); probable 436 (44%); possible 481 (49%); and unlikely 7 (1%). 125 different drugs were definitely or probably related to agranulocytosis. Drugs for which >10 reports were available (carbimazole, clozapine, dapsone, dipyrone, methimazole, penicillin g, procainamide, propylthiouracil, rituximab, sulfasalazine, ticlopidine) accounted for >50% of definite or probable reports. Proportions of fatal cases decreased between 1966 and 2006. More cases with a neutrophil nadir <100/µl had fatal complications than those with a nadir > 100/µl (10% versus 3%, p<0.001). Cases reporting treatment with hematopoietic growth factors had a shorter median duration of neutropenia (8 days versus 9 days; p=0.015) and, among asymptomatic patients at diagnosis, had a lower proportion of infectious or fatal complications (14% treated versus 29% untreated; p=0.030) than those that did not report such treatment.
Conclusions: Several drugs can cause non-chemotherapy drug-induced agranulocytosis. Patients with a neutrophil count <100/µl are particularly at risk of developing life threatening complications. Associated mortality may be decreasing over time with the availability of better treatment including hematopoietic growth factors.
