Stephan F, Podlipski M-A, Kerleau J-M, Petit M, Guillin O
Service universitaire de psychiatrie, centre hospitalier du Rouvray,76300 Sotteville-lès-Rouen, France.
Encephale. 2009 Apr;35(2):173-5. doi: 10.1016/j.encep.2008.04.003. Epub 2008 Aug 19.
We report the case of a 50-year-old man, treated with chlorpromazine for schizophrenia, who developed an agranulocytosis. Three mechanisms of drugs-induced agranulocytosis have been reported: toxic, genetic and immune. Phenothiazines are responsible for drug-induced agranulocytosis. This patient had been treated with first and second generation antipsychotic drugs during his life and had already been exposed to chlorpromazine or other phenotiazines without any signs of toxicity. However, two months after the introduction of chlorpromazine he presented an agranulocytosis (leukocytes 1.4G/L and neutrophils 0.2G/L). After discontinuation of chlorpromazine, blood count returned to normal. The role of chlorpromazine in inducing toxic agranulocytosis was based on: (i) normal blood count before the introduction of chlorpromazine; (ii) occurrence of agranulocytosis within the first weeks of chlorpromazine treatment; (iii) normal bone marrow and blood count after discontinuation of chlorpromazine; (iv) chlorpromazine was the only new drug prescribed to this patient at the time the agranulocytosis occurred. Risk factors for toxic agranulocytosis in this patient were: old age, association of phenothiazine with other drugs known to be able to induce agranulocytosis, and past history of use of high doses of chlorpromazine.
This case report highlights the risk of chlorpromazine in inducing agranulocytosis, a risk underestimated in regard of the clozapine risk to induce agranulocytosis or neutropenia. For this reason, it seems reasonable to recommend performing a blood count before introduction of phenothiazine in patients with risk factors for toxic drug-induced agranulocytosis (old age, female, receiving other drugs with a high potential to induce agranulocytosis and having received high doses of phenothiazine for a long time).
我们报告一例50岁男性，因精神分裂症接受氯丙嗪治疗，发生了粒细胞缺乏症。药物性粒细胞缺乏症有三种机制被报道：毒性、遗传和免疫机制。吩噻嗪类药物是药物性粒细胞缺乏症的病因。该患者一生中曾接受第一代和第二代抗精神病药物治疗，且已接触过氯丙嗪或其他吩噻嗪类药物，未出现任何毒性迹象。然而，在使用氯丙嗪两个月后，他出现了粒细胞缺乏症（白细胞1.4G/L，中性粒细胞0.2G/L）。停用氯丙嗪后，血常规恢复正常。氯丙嗪诱导毒性粒细胞缺乏症的依据为：（i）使用氯丙嗪前血常规正常；（ii）氯丙嗪治疗最初几周内出现粒细胞缺乏症；（iii）停用氯丙嗪后骨髓和血常规正常；（iv）粒细胞缺乏症发生时，氯丙嗪是该患者唯一新开的药物。该患者发生毒性粒细胞缺乏症的危险因素为：老年、吩噻嗪类药物与其他已知可诱导粒细胞缺乏症的药物联用，以及既往使用高剂量氯丙嗪的病史。
本病例报告强调了氯丙嗪诱导粒细胞缺乏症的风险，相对于氯氮平诱导粒细胞缺乏症或中性粒细胞减少症的风险，该风险被低估了。因此，对于有药物性毒性粒细胞缺乏症危险因素（老年、女性、正在接受其他有高诱导粒细胞缺乏症可能性的药物治疗且长期接受高剂量吩噻嗪类药物治疗）的患者，在使用吩噻嗪类药物前建议进行血常规检查似乎是合理的。
