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流式细胞术检测高残余血小板反应性对接受氯吡格雷治疗的缺血性中风患者预后的预测价值

Predictive value of high residual platelet reactivity by flow cytometry for outcomes of ischemic stroke patients on clopidogrel therapy.

作者信息

Qiu Li-Na, Wang Lin, Li Xin, Han Rui-Fa, Xia Xiao-Shuang, Liu Jie

机构信息

Department of Neurology, The Second Hospital of Tianjin Medical University, Tianjin, China.

Department of Geratology, The Second Hospital of Tianjin Medical University, Tianjin, China; Tianjin Institute of Geratology, Tianjin, China.

出版信息

J Stroke Cerebrovasc Dis. 2015 Jun;24(6):1145-52. doi: 10.1016/j.jstrokecerebrovasdis.2015.01.004. Epub 2015 Apr 11.

DOI:10.1016/j.jstrokecerebrovasdis.2015.01.004
PMID:25869773
Abstract

High residual platelet reactivity (HRPR) assessed by multiple tests has been associated with worse clinical outcomes. However, the clinical impact of HRPR assessed by flow cytometry is unknown. The aim of this study was to validate the predictive value of HRPR measured by flow cytometry for clinical outcomes in ischemic stroke patients during clopidogrel therapy. Overall, 198 consecutive patients with ischemic stroke taking clopidogrel underwent platelet function testing on flow cytometer including adenosine diphosphate (ADP)-induced platelet aggregation (PAg) and platelet activation markers (CD62P, CD63, and PAC-1). Poor outcome was defined as poor prognosis and ischemic events during 12-month follow-up. By receiver operating characteristic curve analysis, residual platelet reactivity assessed by flow cytometry was able to distinguish between patients with and without poor outcomes, when platelet inhibition was evaluated with ADP-PAg (area under the curve [AUC], .77; 95% confidence interval [CI], .69-.84; P < .001), CD62P (AUC, .73; 95% CI, .64-.81; P < .001), CD63 (AUC, .72; 95% CI, .64-.80; P < .001), and PAC-1 (AUC, .70; 95% CI, .62-.78; P < .001). The prevalence of HRPR was 25.8% for ADP-PAg, 32.8% for CD62P, 41.4% for CD63, and 56.1% for PAC-1. The multiple logical regression analysis demonstrated that HRPR was an independent predictor of poor outcomes (ADP-PAg: odds ratio [OR] 13.03, 95% CI 5.66-29.98, P < .001; CD62P: OR 8.55, 95% CI 3.94-18.57, P < .001; CD63: OR 8.74, 95% CI 3.89-19.64, P < .001; PAC-1: OR 4.23, 95% CI 1.98-9.08). In conclusion, HRPR, assessed by flow cytometry, is able to detect ischemic stroke patients at increased risk of 12-month poor outcomes on clopidogrel treatment.

摘要

通过多种检测评估的高残余血小板反应性(HRPR)与较差的临床结局相关。然而,通过流式细胞术评估的HRPR的临床影响尚不清楚。本研究的目的是验证通过流式细胞术测量的HRPR对氯吡格雷治疗期间缺血性中风患者临床结局的预测价值。总体而言,198例连续服用氯吡格雷的缺血性中风患者在流式细胞仪上进行了血小板功能检测,包括二磷酸腺苷(ADP)诱导的血小板聚集(PAg)和血小板活化标志物(CD62P、CD63和PAC-1)。不良结局定义为12个月随访期间预后不良和缺血事件。通过受试者工作特征曲线分析,当用ADP-PAg(曲线下面积[AUC],0.77;95%置信区间[CI],0.69-0.84;P < 0.001)、CD62P(AUC,0.73;95% CI,0.64-0.81;P < 0.001)、CD63(AUC,0.72;95% CI,0.64-0.80;P < 0.001)和PAC-1(AUC,0.70;95% CI,0.62-0.78;P < 0.001)评估血小板抑制时,通过流式细胞术评估的残余血小板反应性能够区分有无不良结局的患者。ADP-PAg的HRPR患病率为25.8%,CD62P为32.8%,CD63为41.4%,PAC-1为56.1%。多逻辑回归分析表明,HRPR是不良结局的独立预测因素(ADP-PAg:比值比[OR] 13.03,95% CI 5.66-29.98,P < 0.001;CD62P:OR 8.55,95% CI 3.94-18.57,P < 0.001;CD63:OR 8.74,95% CI 3.89-19.64,P < 0.001;PAC-1:OR 4.23,95% CI 1.98-9.08)。总之,通过流式细胞术评估的HRPR能够检测出氯吡格雷治疗12个月预后不良风险增加的缺血性中风患者。

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