Institute of Pharmaceutical Science, King's College London, London, UK.
Pharmacy Department, South London and Maudsley NHS Foundation Trust, London, UK.
J Psychopharmacol. 2024 Jul;38(7):624-635. doi: 10.1177/02698811241262767. Epub 2024 Jul 23.
Clozapine is known to cause agranulocytosis. Mandatory monitoring schemes are aimed at reducing the risk of agranulocytosis and of the consequences of agranulocytosis. All cases of agranulocytosis occurring in people prescribed clozapine are assumed to be caused by clozapine.
In a previous study, we examined a cohort of patients listed on our hospital database as having had clozapine-induced agranulocytosis and applied specific criteria to identify those with confirmed clozapine-related, life-threatening agranulocytosis. In this study, we examine the cases not meeting these specific criteria.
In the original study, 9 of 23 cases met the criteria for clozapine-induced, life-threatening agranulocytosis. Of the 13 remaining cases for whom data were available, 5 were probably caused by clozapine but were not life-threatening. Three cases were the result of concomitant cancer chemotherapy. Three were anomalous results probably related to measurement error. For the remaining two cases, the cause was not identified.
Not all cases of agranulocytosis occurring in people taking clozapine are caused by clozapine. The widely used threshold criterion-based diagnosis overestimates the risk of agranulocytosis. True clozapine-related agranulocytosis is best identified by pattern-based criteria: rapid fall in neutrophil counts over around 2 weeks to below 0.5 × 109/L for two consecutive days (unless clozapine is stopped very early or granulocyte colony stimulating factor is given) where other possible causes (benign ethnic neutropenia, cancer chemotherapy) can be ruled out.
氯氮平已知可引起粒细胞缺乏症。强制性监测方案旨在降低粒细胞缺乏症和粒细胞缺乏症后果的风险。假定所有服用氯氮平的患者出现的粒细胞缺乏症均由氯氮平引起。
在之前的一项研究中，我们检查了我们医院数据库中列出的因氯氮平引起的粒细胞缺乏症患者队列，并应用特定标准来识别那些具有确诊的氯氮平相关、危及生命的粒细胞缺乏症的患者。在本研究中，我们检查了不符合这些特定标准的病例。
在原始研究中，23 例中有 9 例符合氯氮平引起的危及生命的粒细胞缺乏症标准。在其余 13 例有数据可用的病例中，5 例可能由氯氮平引起，但不危及生命。3 例是由于同时进行癌症化疗所致。3 例是可能与测量误差有关的异常结果。对于其余 2 例，病因未确定。
并非所有服用氯氮平的患者发生的粒细胞缺乏症均由氯氮平引起。广泛使用的基于阈值标准的诊断高估了粒细胞缺乏症的风险。通过基于模式的标准可最好地识别真正的氯氮平相关粒细胞缺乏症：中性粒细胞计数在大约 2 周内迅速下降至连续两天低于 0.5×109/L（除非氯氮平非常早停用或给予粒细胞集落刺激因子），排除其他可能的原因（良性种族中性粒细胞减少症、癌症化疗）。
