Duwez M, Szymanski G, Carre M, Mallaret M, Lepelley M
Département de pharmacie, CHU de Grenoble-Alpes, 38000 Grenoble, France.
Laboratoire d'hématologie, CHU de Grenoble-Alpes, 38000 Grenoble, France.
Ann Pharm Fr. 2020 May;78(3):230-241. doi: 10.1016/j.pharma.2020.02.004. Epub 2020 Feb 10.
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.
特发性药物性粒细胞缺乏症是一种罕见但可能严重的血液系统疾病。其病理生理机制复杂,了解甚少。我们旨在通过对过去七年在我校医院进行的有“髓系成熟停滞”表现的骨髓涂片检查来研究与粒细胞缺乏症相关的药物原因。
对2010年1月1日至2016年12月31日期间收集的用于粒细胞缺乏症诊断的骨髓涂片进行回顾性分析。我们采用贝高德等人的方法进行药物因果关系评估。
在分析的104份骨髓涂片中,41例粒细胞缺乏症是药物引起的,其中28例为特发性。在这28例病例中,涉及26种不同药物。24种药物的产品特性总结中已知粒细胞缺乏症是一种不良反应,主要与未确定频率相关(n = 7)。平均发病潜伏期为开始用药后38.1天(n = 23例计算得出),50%的病例使用了粒细胞生长因子,但并未缩短平均血细胞计数恢复延迟时间。29%的病例骨髓呈现嗜酸性粒细胞增多。药物警戒报告率为48%。
骨髓涂片中的“成熟停滞”并非特发性药物性粒细胞缺乏症的特征性表现。这一罕见事件需要血液科医生、生物学家和药物警戒专家的多学科护理。与常见药物不良反应报告率(5%至10%)相比,粒细胞缺乏症报告率较高,可能与该事件的潜在严重性有关。