Ahn Yong Min, Jeong Seong Hoon, Jang Hong Suk, Koo Young Jin, Kang Ung Gu, Lee Kyu Young, Kim Yong Sik
Department of Psychiatry, Seoul National University College of Medicine, Seoul, South Korea.
Int Clin Psychopharmacol. 2004 Mar;19(2):97-101. doi: 10.1097/00004850-200403000-00007.
According to the recommended guidelines by Novartis, neutropenia in the range of a white blood cell count less than 3000 per mm, or an absolute neutrophil count (ANC) less than 1500 per mm, is classified as being in the 'red-alert zone' during clozapine treatment. If a patient's blood test result falls into this zone, immediate discontinuation of clozapine is recommended, and reinstitution is prohibited. However, in some patients, it is not entirely feasible to implement this standard guideline because of the lack of effective alternatives to clozapine treatment. Through retrospective chart reviews, five patients who had been maintained on clozapine treatment despite red-alert zone neutropenia were selected. The haematological and clinical courses of these patients were followed for more than 600 days and were compared with those of two control patients who discontinued clozapine due to neutropenia. In all five patients, no additional episodes of neutropenia occurred during the observation period despite continued clozapine treatment. However, three of them maintained a lower neutrophil count for the remaining observation period. Four patients responded favourably to clozapine treatment as judged by Clinical Global Impression score. Given the limitations of a retrospective chart review and the small number of patients, we cannot draw any definite conclusions. However, while the guidelines for the prevention of agranulocytosis should be generally followed, it may be that judicious continuation of clozapine treatment is less risk-prone than previously considered in selected cases where only a few feasible alternatives to clozapine are available. Moreover, there is an apparent necessity to develop new measures or methods that can differentiate between benign neutropenia and that leading to fatal agranulocytosis.
根据诺华公司推荐的指南，在氯氮平治疗期间，白细胞计数低于每立方毫米3000或绝对中性粒细胞计数（ANC）低于每立方毫米1500的中性粒细胞减少症被归类为处于“红色警戒区”。如果患者的血液检测结果落入该区域，建议立即停用氯氮平，且禁止重新使用。然而，在一些患者中，由于缺乏氯氮平治疗的有效替代方案，实施这一标准指南并不完全可行。通过回顾性病历审查，选择了五名尽管处于红色警戒区中性粒细胞减少症但仍接受氯氮平治疗的患者。对这些患者的血液学和临床病程进行了600多天的跟踪，并与两名因中性粒细胞减少症而停用氯氮平的对照患者进行了比较。在所有五名患者中，尽管继续使用氯氮平治疗，但在观察期内未发生额外的中性粒细胞减少症发作。然而，其中三名患者在剩余的观察期内中性粒细胞计数维持在较低水平。根据临床总体印象评分判断，四名患者对氯氮平治疗反应良好。鉴于回顾性病历审查的局限性和患者数量较少，我们无法得出任何明确的结论。然而，虽然预防粒细胞缺乏症的指南通常应遵循，但在只有少数氯氮平可行替代方案的特定病例中，明智地继续使用氯氮平治疗可能比以前认为的风险更低。此外，显然有必要开发新的措施或方法，以区分良性中性粒细胞减少症和导致致命粒细胞缺乏症的中性粒细胞减少症。
