流式细胞术和血栓弹力图检测对冠心病经皮冠状动脉介入术后氯吡格雷的反应性评估

摘要

Objective To explore flow cytometry and Thrombelastogram(TEG)testing value in evaluation of low re-sponse to clopidogrel. Methods Eighty - nine patients with coronary heart disease(CHD) admitted to Fuxing Hospital from February to December 2011 were enrolled in study group,29 healthy subjects in control group. After 1 - week administration of clopidogrel and aspirin,flow cytometry and TEG were used to detect clopidogrel response,flow cytometry to test platelet activated receptor maker PAC - 1 and CD62p,TEG to test ADP inhibition rate which reflected the clopidogrel effect. The incidences of is-chemia and bleeding events within 1 year were followed up. Results The expressions of platelet activation markers were calculat-ed according to interquartile range method. Defining platelet activation marker CD62p > 15. 5% and PAC - 1 > 3. 01% as high expression of platelet activation,the response to clopidogrel was low;platelet activation marker CD62p > 15. 5% or PAC - 1 >3. 01% for moderate expression of activated platelets ;defining CD62P < 15. 5% or PAC - 1 < 3. 01% as medium expression or as low expression,the response to clopidogrel was better. When ADP inhibition ratio was 38. 9% ,the sensitivity was 97. 0% , specificity 61. 1% ,the area under ROC curve was 0. 932(P = 0. 001). Forty - six patients had high expression,43 had medi-um,no patients had low expression. Combined with ADP inhibition rate < 38. 9% ,40 patients had low response to clopidogrel. There was no significant difference in incidences of major ischemia and bleeding events between patients with low,medium re-sponses(P > 0. 05). Only 4 patients had mild bleeding events,mainly local subcutaneous hemorrhage,gum bleeding,subhya-loid hemorrhage. Conclusion The critical value of TEG detecting low response to clopidogrel is ADP < 38. 9% ,suggesting that patients may have drug resistance,which provides references for further researches.%目的：探讨流式细胞术和血栓弹力图（TEG）检测对冠心病经皮冠状动脉介入术后氯吡格雷反应性的评估价值。方法入选2011年2-12月首都医科大学附属复兴医院心内科收治住院，诊断为冠心病并行经皮冠状动脉介入术（PCI），且术后行常规抗血小板治疗并同意参与本研究的患者89例作为观察组，同时选取该院同期体检健康者29例作为对照组。患者均在术后连续7 d 联合服用氯吡格雷和阿司匹林，采用流式细胞术和 TEG 检测患者术后服用氯吡格雷的反应性。流式细胞术检测血小板活化标志物 PAC -1和 CD62p 受体，TEG 检测反映氯吡格雷效果的二磷酸腺苷（ADP）抑制率，同时随访患者1年内缺血事件和出血事件发生率。结果根据统计学四分位数间距法计算血小板活化标记物表达量，定义血小板活化标记物 CD62p >15.5%同时 PAC -1>3.01%为血小板活化程度高表达，代表氯吡格雷反应性较低；血小板活化标记物 CD62p >15.5%或者 PAC -1>3.01%为血小板活化程度中等表达；血小板活化标记物 CD62p <15.5%或者 PAC -1<3.01%为血小板活化程度低表达，代表氯吡格雷反应性较好。评估 TEG 检测方法，当 ADP 抑制率为38.9%时灵敏度为97.0%、特异度为61.1%，ROC 曲线下面积为0.932（P =0.001）。血小板活化程度高表达患者46例，中等表达患者43例，无低表达患者。结合 ADP 抑制率<38.9%，40例患者氯吡格雷反应性较低。反应性较低的患者与反应性中等的患者缺血事件发生率和出血事件发生率比较，差异均无统计学意义（ P >0.05）。所有随访患者仅4例发生轻度出血事件，主要表现为局部皮下出血、牙龈出血和眼底出血。结论 TEG 检测患者对氯吡格雷反应性低下的临界值为 ADP 抑制率<38.9%，提示患者可能存在药物抵抗，为进一步研究提供了参考依据。