13例甲巯咪唑致粒细胞缺乏症伴发热回顾性分析
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摘要
目的:探讨甲巯咪唑用于甲状腺功能亢进症患者时所致粒细胞缺乏症伴发热的临床特征及治疗对策,为临床合理用药提供参考。方法:对某三级甲等医院收治的13例使用甲巯咪唑出现粒细胞缺乏症伴发热的甲状腺功能亢进症患者的病历资料进行回顾性分析。结果:13例患者均符合甲状腺功能亢进症的诊断标准,其中,初次服用甲巯咪唑者11例,复发后再次用药者1例,6年前行~(131)Ⅰ放射治疗后复发再次用药者1例;男女之比为1∶12;年龄19～66岁,平均(44.6±14.1)岁。甲巯咪唑所致粒细胞缺乏症伴发热多出现于用药初的1～2个月内,临床表现为发热,多伴咽痛、扁桃体化脓等上呼吸道感染症状,严重者出现败血症,及早发现并及时治疗;经验性使用广谱、高效抗菌药物治疗感染,并使用粒细胞集落刺激因子升高粒细胞计数,可提高临床治愈率。结论:临床应高度重视甲巯咪唑所致粒细胞缺乏症伴发热的严重不良反应,加强对患者的用药宣教,用药期间密切监测患者的血常规,防止或减少严重不良反应的发生;一旦出现粒细胞缺乏症伴发热的症状,应立即停药,并采取积极有效的综合治疗措施,保证患者用药安全。
OBJECTIVE: To investigate the clinical characteristics and treatment of agranulocytosis complicated with fever induced by methimazole in patients with hyperthyroidism, so as to provide reference for rational drug use in clinic. METHODS: Retrospective analysis was performed on the medical records of 13 hyperthyroidism patients with agranulocytosis complicated with fever induced by methimazole in grade Ⅲ level A hospital. RESULTS: All the 13 patients met the diagnostic criteria for hyperthyroidism. Among them, 11 patients were treated with methimazole for the first time, 1 patient was re-administered after relapse, and 1 patient was relapsed after ~(131)I radiation therapy of 6 years ago. The ratio of male to female was 1∶12; the age was from 19 to 66 years old, with an average of(44.6±14.1) years. Agranulocytosis complicated with fever induced by methimazole mostly occurred in the first 1 to 2 months of treatment, with clinical manifestations of fever, pharyngeal pain, tonsil pyesis and other upper respiratory tract infection symptoms, and sepsis in severe cases, which should be detected early and treated in time. The clinical cure rate can be improved by the treatment of infection with broad spectrum and high efficiency antibiotics and the increase of granulocyte colony stimulating factor. CONCLUSIONS: In clinical practice, it is necessary to attach great importance to the severe adverse drug reactions of agranulocytosis complicated with fever induced by methimazole, strengthen the education of patients on medication, closely monitor the blood routine of patients during medication, and prevent or reduce the occurrence of severe adverse drug reactions. In case of agranulocytosis complicated with fever, the drug should be stopped immediately, and active and effective comprehensive treatment measures should be taken to ensure the drug safety of patients.
OBJECTIVE: To investigate the clinical characteristics and treatment of agranulocytosis complicated with fever induced by methimazole in patients with hyperthyroidism, so as to provide reference for rational drug use in clinic. METHODS: Retrospective analysis was performed on the medical records of 13 hyperthyroidism patients with agranulocytosis complicated with fever induced by methimazole in grade Ⅲ level A hospital. RESULTS: All the 13 patients met the diagnostic criteria for hyperthyroidism. Among them, 11 patients were treated with methimazole for the first time, 1 patient was re-administered after relapse, and 1 patient was relapsed after ~(131)I radiation therapy of 6 years ago. The ratio of male to female was 1∶12; the age was from 19 to 66 years old, with an average of(44.6±14.1) years. Agranulocytosis complicated with fever induced by methimazole mostly occurred in the first 1 to 2 months of treatment, with clinical manifestations of fever, pharyngeal pain, tonsil pyesis and other upper respiratory tract infection symptoms, and sepsis in severe cases, which should be detected early and treated in time. The clinical cure rate can be improved by the treatment of infection with broad spectrum and high efficiency antibiotics and the increase of granulocyte colony stimulating factor. CONCLUSIONS: In clinical practice, it is necessary to attach great importance to the severe adverse drug reactions of agranulocytosis complicated with fever induced by methimazole, strengthen the education of patients on medication, closely monitor the blood routine of patients during medication, and prevent or reduce the occurrence of severe adverse drug reactions. In case of agranulocytosis complicated with fever, the drug should be stopped immediately, and active and effective comprehensive treatment measures should be taken to ensure the drug safety of patients.
引文
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[2] 李岚,夏东胜,田春华,等.甲巯咪唑片安全性风险的分析及思考[J].中国药物警戒,2018,15(7):393-397.
[3] 李祥霞.136例甲巯咪唑不良反应报告分析[J].临床药物治疗杂志,2011,9(3):53-55.
[4] 彭丽丽,刘巍,汤韧,等.甲巯咪唑药品不良反应/事件文献分析[J].中国药物警戒,2018,15(7):405-410.
[5] 文晓玲,高云娟,张海浪,等.甲巯咪唑致粒细胞减少不良反应分析[J].中国药物警戒,2018,15(7):398-403.
[6] 王晓虹,马建丽,罗艳,等.甲巯咪唑的严重不良反应及处理对策[J].实用药物与临床,2014,17(12):1604- 1606.
[7] 柴晓峰,连小兰.抗甲状腺药物治疗导致粒细胞缺乏症36例患者临床资料分析[J].医学研究杂志,2017,46(3):87-90.
[8] 胡紫娟.甲巯咪唑致甲状腺功能亢进患者粒细胞缺乏症12例临床治疗分析[J].解放军预防医学杂志,2016,34(S1):272.
[9] 冯淑娴,鲁琼.3例甲巯咪唑致粒细胞缺乏症合并感染的治疗分析[J].中南药学,2014,12(9):928-931.
[10] 中华医学会血液学分会,中国医师协会血液科医师分会.中国中性粒细胞缺乏伴发热患者抗菌药物临床应用指南(2016年版)[J].中华血液学杂志,2016,37(5):353-359.
[11] Watanabe N,Narimatsu H,Noh JY,et al.Antithyroid drug-induced hematopoietic damage:a retrospective cohort study of agranulo-cytosis and pancytopenia involving 50 385 patients with Graves’ disease[J].J Clin Endocrinol Metab,2012,97(1):E49-E53.
[12] Takata K,Kubota S,Fukam S,et al.Methimazole-induced agran-ulocytosis in patients with Graves’ disease is more frequent with an initial dose of 30 mg daily than with 15 mg daily[J].Thyroid,2009,19(6):559-563.
[13] 何珂,朱丽华,陆西宛.初诊断Graves病患者白细胞或中性粒细胞减少与TRAb相关性研究[J].免疫学杂志,2016,32(7):611-615.
[14] 范景丽,马玉琴,汪春雷,等.121例亚急性甲状腺炎患者流行病学及临床特点的回顾性分析[J].中华地方病学杂志,2017,36(5):338-341.
[15] 中国医药教育协会感染疾病专业委员会.抗菌药物药代动力学/药效学理论临床应用专家共识[J].中华结核和呼吸杂志,2018,41(6):409-446.
[2] 李岚,夏东胜,田春华,等.甲巯咪唑片安全性风险的分析及思考[J].中国药物警戒,2018,15(7):393-397.
[3] 李祥霞.136例甲巯咪唑不良反应报告分析[J].临床药物治疗杂志,2011,9(3):53-55.
[4] 彭丽丽,刘巍,汤韧,等.甲巯咪唑药品不良反应/事件文献分析[J].中国药物警戒,2018,15(7):405-410.
[5] 文晓玲,高云娟,张海浪,等.甲巯咪唑致粒细胞减少不良反应分析[J].中国药物警戒,2018,15(7):398-403.
[6] 王晓虹,马建丽,罗艳,等.甲巯咪唑的严重不良反应及处理对策[J].实用药物与临床,2014,17(12):1604- 1606.
[7] 柴晓峰,连小兰.抗甲状腺药物治疗导致粒细胞缺乏症36例患者临床资料分析[J].医学研究杂志,2017,46(3):87-90.
[8] 胡紫娟.甲巯咪唑致甲状腺功能亢进患者粒细胞缺乏症12例临床治疗分析[J].解放军预防医学杂志,2016,34(S1):272.
[9] 冯淑娴,鲁琼.3例甲巯咪唑致粒细胞缺乏症合并感染的治疗分析[J].中南药学,2014,12(9):928-931.
[10] 中华医学会血液学分会,中国医师协会血液科医师分会.中国中性粒细胞缺乏伴发热患者抗菌药物临床应用指南(2016年版)[J].中华血液学杂志,2016,37(5):353-359.
[11] Watanabe N,Narimatsu H,Noh JY,et al.Antithyroid drug-induced hematopoietic damage:a retrospective cohort study of agranulo-cytosis and pancytopenia involving 50 385 patients with Graves’ disease[J].J Clin Endocrinol Metab,2012,97(1):E49-E53.
[12] Takata K,Kubota S,Fukam S,et al.Methimazole-induced agran-ulocytosis in patients with Graves’ disease is more frequent with an initial dose of 30 mg daily than with 15 mg daily[J].Thyroid,2009,19(6):559-563.
[13] 何珂,朱丽华,陆西宛.初诊断Graves病患者白细胞或中性粒细胞减少与TRAb相关性研究[J].免疫学杂志,2016,32(7):611-615.
[14] 范景丽,马玉琴,汪春雷,等.121例亚急性甲状腺炎患者流行病学及临床特点的回顾性分析[J].中华地方病学杂志,2017,36(5):338-341.
[15] 中国医药教育协会感染疾病专业委员会.抗菌药物药代动力学/药效学理论临床应用专家共识[J].中华结核和呼吸杂志,2018,41(6):409-446.