Andersohn Frank, Konzen Christine, Garbe Edeltraut
Department of Clinical Pharmacology and Toxicology, Charité-Universitaetsmedizin Berlin, Berlin, Germany.
Ann Intern Med. 2007 May 1;146(9):657-65. doi: 10.7326/0003-4819-146-9-200705010-00009.
Nonchemotherapy drug-induced agranulocytosis is a rare adverse reaction that is characterized by a decrease in peripheral neutrophil count to less than 0.5 x 10(9) cells/L due to immunologic or cytotoxic mechanisms.
To systematically review case reports of drugs that are definitely or probably related to agranulocytosis.
English-language and German-language reports in MEDLINE (1966 to 2006) or EMBASE (1989 to 2006) and in bibliographies of retrieved articles.
Published case reports of patients with nonchemotherapy drug-induced agranulocytosis.
One reviewer abstracted details about cases and assessed causality between drug intake and agranulocytosis by using World Health Organization assessment criteria.
Causality assessments of 980 reported cases of agranulocytosis were definite in 56 (6%), probable in 436 (44%), possible in 481 (49%), and unlikely in 7 (1%). A total of 125 drugs were definitely or probably related to agranulocytosis. Drugs for which more than 10 reports were available (carbimazole, clozapine, dapsone, dipyrone, methimazole, penicillin G, procainamide, propylthiouracil, rituximab, sulfasalazine, and ticlopidine) accounted for more than 50% of definite or probable reports. Proportions of fatal cases decreased between 1966 and 2006. More patients with a neutrophil count nadir less than 0.1 x 10(9) cells/L had fatal complications than did those with a neutrophil count nadir of 0.1 x 10(9) cells/L or greater (10% vs. 3%; P < 0.001). Patients treated with hematopoietic growth factors had a shorter median duration of neutropenia (8 days vs. 9 days; P = 0.015) and, among asymptomatic patients at diagnosis, had a lower proportion of infectious or fatal complications (14% vs. 29%; P = 0.030) than patients without such treatment.
Case reports cannot provide rates of drug-induced complications, sometimes incompletely assess or describe important details, and sometimes emphasize atypical features and outcomes.
Many drugs can cause nonchemotherapy drug-induced agranulocytosis. Case fatality may be decreasing over time with the availability of better treatment.
非化疗药物所致粒细胞缺乏症是一种罕见的不良反应，其特征是由于免疫或细胞毒性机制导致外周血中性粒细胞计数降至低于0.5×10⁹/L。
系统回顾肯定或可能与粒细胞缺乏症相关的药物的病例报告。
MEDLINE（1966年至2006年）或EMBASE（1989年至2006年）中的英文和德文报告以及检索文章的参考文献。
已发表的非化疗药物所致粒细胞缺乏症患者的病例报告。
一名研究者提取病例详细信息，并使用世界卫生组织评估标准评估药物摄入与粒细胞缺乏症之间的因果关系。
980例报告的粒细胞缺乏症病例的因果关系评估为肯定的有56例（6%），很可能的有436例（44%），可能的有481例（49%），不太可能的有7例（1%）。共有125种药物肯定或很可能与粒细胞缺乏症相关。有超过10篇报告的药物（卡比马唑、氯氮平、氨苯砜、安乃近、甲巯咪唑、青霉素G、普鲁卡因胺、丙硫氧嘧啶、利妥昔单抗、柳氮磺胺吡啶和噻氯匹定）占肯定或很可能报告的50%以上。1966年至2006年间致命病例的比例有所下降。中性粒细胞计数最低点低于0.1×10⁹/L的患者比中性粒细胞计数最低点为≥0.1×10⁹/L的患者有更多致命并发症（10%对3%；P<0.001）。接受造血生长因子治疗的患者中性粒细胞减少的中位持续时间较短（8天对9天；P=0.015），并且在诊断时无症状的患者中，与未接受此类治疗的患者相比，感染性或致命并发症的比例较低（14%对29%；P=0.030）。
病例报告无法提供药物所致并发症的发生率，有时对重要细节评估或描述不完整，有时强调非典型特征和结果。
许多药物可导致非化疗药物所致粒细胞缺乏症。随着更好治疗方法的出现，病例死亡率可能会随时间下降。
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