氯吡格雷相关胰岛素自身免疫综合征的文献分析  

Literature analysis of clopidogrel-related insulin autoimmune syndrome

作　　者：郑雪[1] 谢娟 杨立莉 辛义明 孙乐乐[1] 刘萍[2] Zheng Xue;Xie Juan;Yang Lili;Xin Yiming;Sun Lele;Liu Ping(Clinical Pharmacy Department,Zibo Central Hospital,Zibo 255036,China;Drug Procurement and Supply Department,Zibo Central Hospital,Zibo 255036,China;Department of Pharmacy,the Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250011,China)

机构地区：[1]淄博市中心医院临床药学科,山东淄博255036 [2]淄博市中心医院药品采购供应科,山东淄博255036 [3]山东中医药大学附属医院药学部,山东济南250011

出　　处：《实用药物与临床》2025年第2期116-121,共6页Practical Pharmacy and Clinical Remedies

基　　金：山东省药品不良反应监测中心科研课题(2024SDADRKY46);山东省药品临床综合评价项目(2022YZ003)。

摘　　要：目的探讨氯吡格雷相关胰岛素自身免疫综合征(Insulin autoimmune syndrome,IAS)的临床特点及治疗转归,为临床用药安全提供参考。方法以氯吡格雷(Clopidogrel)和胰岛素自身免疫综合征(IAS)、低血糖(Hypoglycemia)或自身免疫性低血糖(Autoimmune hypoglycemia)为检索词,检索中国知网、万方数据库、PubMed和Embase等数据库自成立至2024年5月氯吡格雷相关IAS的病例报道,提取患者相关信息进行描述性统计分析。结果共收集到氯吡格雷相关IAS患者15例,平均年龄(72.2±9.5)岁,男性比例86.7%。亚洲患者10例,非亚洲患者5例。基因分型方面,DRB1*04的检出率为100%,DQB1*0302的检出率为30%。DRB1*04中,0406、0403、0404的检出率分别为30%、30%、20%。发病时间1周至数月不等,主要症状均为自发性复发性低血糖。实验室检查均显示高胰岛素水平、胰岛素自身抗体(Insulin autoantibody,IAA)阳性或IAA高滴度。13例患者接受停药、饮食调整、激素治疗后好转,2例重症患者分别接受了血浆置换及免疫吸附。所有患者均痊愈或好转,在后续3个月~3年的随访中均未再出现低血糖。结论氯吡格雷相关IAS为氯吡格雷的罕见不良反应,与DRB1*04、DQB1*0302密切相关,服用氯吡格雷1周至数月后出现非糖尿病性低血糖症状,主要表现为高胰岛素血症、低血糖和胰岛素自身抗体水平升高,视病情程度给予相应治疗,均获得满意疗效。Objective To investigate the clinical characteristics and treatment outcomes of clopidogrel-related insulin autoimmune syndrome(IAS),and to provide references for the safety of clinical drug use.Methods CNKI,Wanfang Database,PubMed and Embase databases were searched(as of May 2024)for case reports on clopidogrelrelated IAS with clopidogrel,IAS,hypoglycemia or autoimmune hypoglycemia as the key words,and patient information was extracted for descriptive statistical analysis.Results A total of 15 patients with clopidogrel-related IAS were collected,with an average age of(72.2±9.5)years and a male proportion of 86.7%.There were 10 Asian patients and 5 non-Asian patients.In genotyping,the detection rate of DRB1*04 was 100%,and the detection rate of DQB1*0302 was 30%.In DRB1*04,the detection rate of 0406,0403 and 0404 were 30%,30%and 20%,respectively.The duration of onset varied from 1 week to several months,and the main symptom was spontaneous recurrent hypoglycemia.Laboratory tests all showed high insulin levels,positive insulin autoantibody(IAA),or high titers of IAA.Totally 13 patients were improved after drug withdrawal,diet adjustment and hormone therapy,and 2 patients with severe disease received plasma exchange and immunosorbent,respectively.All patients were cured or improved,and no symptoms of hypoglycemia occurred during the follow-up of 3 months to 3 years.Conclusion Clopidogrel-related IAS is a rare adverse reaction of clopidogrel,which is closely related to DRB1*04 and DQB1*0302.Non-diabetic hypoglycemia symptoms occur after 1 week to several months of taking clopidogrel,and the main clinical manifestations are hyperinsulinemia,hypoglycemia and elevated IAA levels.Treatments are given according to the severity of the diseases,and the prognosis is good.

关 键 词：氯吡格雷 胰岛素自身免疫综合征 低血糖 基因分型 

分 类 号：R58[医药卫生—内分泌]