基因多态性联合血栓弹力图指导个体化抗血小板治疗缺血性脑卒中的临床研究  

Gene polymorphism combined with thromboelastography in guiding personalized antiplatelet therapy for ischemic stroke

作　　者：毛伦林[1] 季莉莉[1] 马爱金[1] 刘志清[1] 王利惠[1] 张金[1] 王佳佳[1] 黄婷婷 陈文亚[1] Mao Lunlin;Ji Lili;Ma Aijin;Liu Zhiqing;Wang Lihui;Zhang Jin;Wang Jiajia;Huang Tingting;Chen Wenya(Department of Neurology,Affiliated Wujin Hospital of Jiangsu University,Changzhou 213017,Jiangsu Province,China)

机构地区：[1]江苏大学附属武进医院神经内科,徐州医科大学武进临床学院,常州213017

出　　处：《中华老年心脑血管病杂志》2021年第5期511-514,共4页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：常州市卫生和计划生育委员会重大科技项目(ZD201820);常州市武进区科技计划项目(WS201916)。

摘　　要：目的探讨基于药物基因多态性联合血栓弹力图(TEG)指导个体化抗血小板治疗急性轻型缺血性脑卒中(IS)患者的有效性及安全性。方法收集急性轻型IS患者250例,随机分为试验组和对照组,每组125例。试验组在第1天采用PCR和Sanger法测序技术检测阿司匹林抵抗(AR)、氯吡格雷抵抗(CR)相关的基因多态性位点,第8天采用TEG检测血小板抑制率,基于药物基因多态性联合TEG指导个体化抗血小板治疗,对照组给予常规抗血小板治疗。随访90 d,观察2组心脑血管事件和出血事件发生率。结果经环氧化酶1(COX-1)、整合素B3(ITGB3)基因检测发现试验组携带AR相关等位基因65例(52.0%),细胞色素P2C19氯吡格雷弱代谢型71例(56.8%)。同时携带AR和氯吡格雷弱代谢型基因患者33例(26.4%)。治疗第8天,TEG检测发现AR 3例(2.4%),均不携带COX-1和ITGB3的变异型等位基因;CR 12例(9.6%),未发现同时有AR和CR的患者。随访90 d,试验组新发脑卒中、复合血管事件及新发IS发生率明显低于对照组(3.2%vs 9.6%,4.0%vs 11.2%,3.2%vs 9.6%,P<0.05)。结论根据药物基因多态性联合TEG指导轻型IS抗血小板治疗能有效降低90 d内新发IS风险,且不增加出血风险。Objective To study the efficiency and safety of drug gene polymorphism combined with thromboelastography in guiding personalized antiplatelet therapy for acute mild IS patients.Methods Two hundred and fifty acute mild IS patients were randomly divided into experimental group(n=125)and control group(n=125).The aspirin resistance(AR)and clopidogrel resistance(CR)-related gene polymorphism sites in experimental group were detected by PCR and Sanger sequencing technique on day 1 after treatment.The platelet aggregation rate was assayed by thromboelastography in experimental group on day 8 after treatment.The patients in experimental group received personalized antiplatelet therapy guided by drug gene polymorphism combined with thromboelastography and those in control group received conventional antiplatelet therapy.The patients were followed up for 90 days,during which the incidence of cardiocerebrovascular events and bleeding events was recorded.Results The detection of COX-1 and ITGB3 gene showed that 65 patients carried AR-related alleles.The detection of CYP2C19 gene showed weak clopidogrel metabolic type in 71 patients.Thirty-three patients carried both AR and weak clopidogrel metabolism-related alleles.Thromboelastography displayed that 3 patients with AR and 12 patients with CR did not carry COX-1 and ITGB3 variant alleles,and no patient with both AR and CR carried COX-1 and ITGB3 variant alleles on day 8 after treatment.The incidence of new cerebral stroke,complex vascular events and new ischemic stroke was significantly lower in experimental group than in control group during the 90-day follow-up period(3.2%vs 9.6%,4.0%vs 11.2%,3.2%vs 9.6%,P<0.05).Conclusion Antiplatelet therapy guided by drug gene polymorphism combined with thromboelastography can effectively reduce the risk of new ischemic stroke with no risk of bleeding in acute mild IS patients during the 90-day follow-up period.

关 键 词：血栓弹力描记术 卒中 血小板聚集抑制剂 整合素类 等位基因 

分 类 号：R743.3[医药卫生—神经病学与精神病学]