DETERMINANTS OF HIGH AND LOW PLATELET RESIDUAL REACTIVITY ON DAY 1-2 OF MYOCARDIAL INFARCTION WHEN TAKING CLOPIDOGREL

T. P. Pronko, V. A. Snezhitskiy, A. V. Kapytski
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Abstract

The aim of the study was to determine the clinical and laboratory factors that determine high and low platelet reactivity in patients taking clopidogrel on day 1-2 of myocardial infarction (MI). Material and Methods. A total of 405 patients (322 men and 83 women) with MI aged 31 to 74 years were examined. Group 1 included patients with low residual platelet reactivity (LRPR) – 89 people, group 2 consisted of patients with optimal platelet reactivity (OPR) – 223 people, group 3 was composed of patients with high residual platelet reactivity (HRPR) – 93 people. Platelet aggregation was assessed on a Multiplate impedance aggregometer (Germany) with several aggregation inducers. A blood test and a study of morphometric parameters of platelets were performed by the cytoflow method on an automated hematology analyzer Sysmex XS-500i (Japan). The study of the level of soluble CD40 ligand (sСD40L) and sP-selectin was performed in 140 patients, von Willebrand factor (VWF) and endothelin-1 were assessed in 150 people on the enzyme immunoassay analyzer Sunrise (TECAN, Austria) using Fine Biotech kits (China). All studies were performed upon admission to the hospital on day 1-2 of MI (at least 12 hours after the administration of a loading dose of clopidogrel). Results. A one-way linear regression analysis identified the following factors that independently affect the value of the ADP-test: age (β=-0.21, 95% CI: -0.42 – -0.0095; p=0.04); total cholesterol (β=1.4, 95% CI: 0.26–2.56; p=0.04); white blood cell count (β= 0.57, 95% CI: 0.003–1.14; p=0.049); hemoglobin (β=-0.16, 95% CI: -0.27 – -0.044; p=0.0067); platelet count (β=1.4, 95% CI: 0.26 – 2.56; p=0.04); PCT (β=76.8, 95% CI: 41.5 – 112.1; p=0.000024); TRAP-test (β=0.4, 95% CI: 0.33–0.46; p<0.000001); CD40L (β=0.044, 95% CI: 0.013–0.074; p=0.005); sP-selectin (β=2.3, 95% CI: 0.63 – 3.97; p=0.007); VWF (β=0.06, 95% CI: 0.016 – 0.11; p=0.0085). To determine the probability of HRPR developing a binary logistic regression model was constructed based on the observational data of a sample of 398 patients, which included the following indicators: age, white blood cell count, mean platelet volume (MPV) and platelet distribution width (PDW) values, results of TRAP-test and the level of creatinine. At the probability cut-off p=0.4746, the sensitivity of the constructed model was 74.2%, specificity - 74.1%, classification accuracy – 74.1%, the area under the ROC-curve – 0.795 (CI: 0.745 – 0.844). To determine the probability of developing LRPR, a binary logistic regression model was constructed based on the observational data of 143 patients, which included the following indicators: the number of leukocytes, MPV and TRAP-test values, fibrinogen and VWF levels. With a probability cut-off p=0.5589, the sensitivity of this model was 84.6%, specificity – 77.8%, classification accuracy – 79.0%, the area under the ROC-curve – 0.826 (CI: 0.747 – 0.905). Conclusion. On days 1-2 of MI, 22% of patients with an excessive response to clopidogrel and 23% with an insufficient response to clopidogrel were identified. The determinants of HRPR are age, white blood cell count, MPV, PDW, TRAP-test and creatinine levels. The determinants of LRPR are white blood cell count, MPV values, spontaneous platelet aggregation, detected by the TRAP-test, the level of fibrinogen and VWF.
服用氯吡格雷后心肌梗死第1-2天血小板残余反应性高低的决定因素
该研究的目的是确定在心肌梗死(MI)第1-2天服用氯吡格雷的患者血小板反应性高低的临床和实验室因素。材料和方法。共检查405例心肌梗死患者(男性322例,女性83例),年龄31 ~ 74岁。1组低残留血小板反应性(LRPR)患者89人,2组最佳残留血小板反应性(OPR)患者223人,3组高残留血小板反应性(HRPR)患者93人。血小板聚集是在多板阻抗聚集计(德国)上评估的,有几个聚集诱导剂。在自动血液学分析仪Sysmex XS-500i(日本)上采用细胞流法进行血液检测和血小板形态计量参数研究。140例患者进行可溶性CD40配体(sСD40L)和sp -选择素水平的研究,150例患者在Sunrise酶免疫分析仪(TECAN,奥地利)上使用Fine Biotech试剂盒(中国)评估血管性血友病因子(VWF)和内皮素-1水平。所有的研究都是在心肌梗死第1-2天入院时进行的(在给予负荷剂量氯吡格雷后至少12小时)。结果。单向线性回归分析确定了以下因素独立影响adp测试值:年龄(β=-0.21, 95% CI: -0.42 - -0.0095;p = 0.04);总胆固醇(β=1.4, 95% CI: 0.26-2.56;p = 0.04);白细胞计数(β= 0.57, 95% CI: 0.003-1.14;p = 0.049);血红蛋白(β=-0.16, 95% CI: -0.27 ~ -0.044;p = 0.0067);血小板计数(β=1.4, 95% CI: 0.26 - 2.56;p = 0.04);PCT (β=76.8, 95% ci: 41.5 - 112.1;p = 0.000024);trap检验(β=0.4, 95% CI: 0.33-0.46;术中,0.000001);Cd40l (β=0.044, 95% ci: 0.013-0.074;p = 0.005);sP-selectin (β=2.3, 95% CI: 0.63 - 3.97;p = 0.007);VWF (β=0.06, 95% ci: 0.016 ~ 0.11;p = 0.0085)。为了确定HRPR发生的概率,我们根据398例患者的年龄、白细胞计数、平均血小板体积(MPV)、血小板分布宽度(PDW)值、trap试验结果、肌酐水平等观察数据,构建二元logistic回归模型。在概率截止点p=0.4746时,构建的模型灵敏度为74.2%,特异性为74.1%,分类准确率为74.1%,roc曲线下面积为0.795 (CI: 0.745 ~ 0.844)。为了确定LRPR发生的概率,基于143例患者的观察数据,包括白细胞数量、MPV和trap测试值、纤维蛋白原和VWF水平,构建二元logistic回归模型。在概率截断p=0.5589的条件下,该模型的敏感性为84.6%,特异性为77.8%,分类准确率为79.0%,roc曲线下面积为0.826 (CI: 0.747 ~ 0.905)。结论。在心肌梗死的第1-2天,22%的患者对氯吡格雷反应过度,23%的患者对氯吡格雷反应不足。HRPR的决定因素有年龄、白细胞计数、MPV、PDW、trap试验和肌酐水平。LRPR的决定因素是白细胞计数、MPV值、自发血小板聚集(通过trap试验检测)、纤维蛋白原水平和VWF。
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