Objective To explore the relationship of platelet activation markers and vitamin D to antiplatelet drug resistance in ischemic stroke patients.Methods From June, 2017 to June, 2018, 190 patients with ischemic stroke were tested their maximum platelet aggregation rate (MPAR) induced by adenosine diphosphate (ADP) and arachidonic acid (AA), activation of platelet CD62P and P-selectin vitamin D seven to ten days after dual antiplatelet treatment (aspirin 100 mg/d + clopidogrel 75 mg/d). According to the MPAR induced by ADP and AA, the patients were divided into resistance group and sensitive group. Results The prevalence of aspirin resistance was 1.2%, while the prevalence of clopidogrel resistance was 24.7% (47 in the resistance group and 143 in the sensitive group). The activation of platelet CD62P (t = -5.232, P < 0.001) and the prevalence of hypertension (χ2 = 4.878, P < 0.05) were more in the resistance group than in the sensitive group, while the vitamin D concentration was less (t = 3.052, P < 0.01). There was no significant difference in P-selectin between the resistance and sensitive groups (t = -0.684, P = 0.253). Logistic regression analyses showed that hypertension (OR = 5.538, 95% CI: 1.204-25.470, P < 0.05), activation of platelet CD62P (OR = 1.082, 95% CI: 1.041-1.092, P < 0.05) and vitamin D (OR = 0.848, 95% CI: 0.755-0.953, P < 0.01) were the independent related factors for clopidogrel resistance. Conclusion Inhibition of platelet activation and supplementation of vitamin D may help to overcome the resistance of clopidogrel.
1 中华医学会神经病学分会,中华医学会神经病学分会脑血管病学组. 中国缺血性脑卒中和短暂性脑缺血发作二级预防指南2014 [J]. 中华神经科杂志, 2015, 48(4): 258-273.
2 KimJ T, HeoS H, ChoiK H, et al. Clinical implications of changes in individual platelet reactivity to aspirin over time in acuteischemic stroke [J]. Stroke, 2015, 46(9): 2534-2540.
3 KimJ T, ChoiK H, ParkM S, et al. Clinical significance of acute and serial platelet function testing in acute ischemic stroke [J]. J Am Heart Assoc, 2018, 7(11): e008313.
4 YiX, LinJ, ZhouQ, et al. Clopidogrel resistance increases rate of recurrent stroke and other vascular events in Chinese population [J]. J Stroke Cerebrovasc Dis, 2016, 25(5): 1222-1228.
5 陈涓涓,陈淮菁,林凯华,等. P选择素、P选择素糖蛋白配体-1及C反应蛋白与青年性脑梗死不同TOAST亚型的关系[J]. 广东医学, 2014, 35(24): 3831-3833.
6 王景尚,孙明月,殷惠军,等. 阿司匹林对波动高糖诱导内皮损伤过程中血小板活化的影响[J]. 中国药理学通报, 2018, 34(1): 50-54.
7 BesterJ, PretoriusE. Effects of IL-1β, IL-6 and IL-8 on erythrocytes, platelets and clot viscoelasticity [J]. Sci Rep, 2016, 6: 32188.
8 SilvagnoF, de VivoE, AttanasioA, et al. Mitochondrial localization of vitamin D receptor in human platelets and differentiated megakaryocytes [J]. PLoS One. 2010, 5(1): e8670.
9 BorstO, MuenzerP, SchmidE, et al. 1,25(OH)2 vitamin D3 dependent inhibition of platelet Ca2+ signaling and thrombus formation on klotho-deficient mice [J]. FASEB J, 2014, 28: 2108-2119.
10 王志军,王硕,王泽宇,等. 介入治疗对冠心病患者血小板活化指标和抗血小板治疗效果及预后的影响研究[J]. 中国全科医学, 2017, 20(33): 4125-4129.
11 王婷婷,陈玮琪,王伊龙. 缺血性脑卒中的精准抗血小板治疗[J]. 精准医学杂志, 2018, 33(1): 86-91.
12 WuX, LiuG, LuJ, et al. Administration of ticagrelor and double-dose clopidogrel based on platelet reactivity determined by verify now-P2Y12 for Chinese subjects after elective PCI [J]. Int Heart J, 2017, 58(2): 167-173.
13 GonzálezA, MonicheF, CayuelaA, et al. Effect of CYP2C19 polymorphisms on the platelet response to clopidogrel and influence on the effect of high versus standard dose clopidogrel in carotid artery stenting [J]. Eur J Vasc Endovasc Surg, 2016, 51(2): 175-186.
14 马丽,李杰,穆叶塞,等. 急诊介入治疗前后AMI患者P选择素和血小板膜糖蛋白GPⅡb/Ⅲa复合物表达研究[J]. 新疆医科大学学报, 2015, 38(9): 1110-1112.
15 胡晓芳,李娜,王玉红,等. 血小板膜糖蛋白与缺血性脑血管病关系的研究[J]. 中国实验诊断学, 2014, 18(12): 1988-1990.
16 黄涛,王海侨. PAC-1、CD62p和D-Dimer含量与急性脑梗死患者梗死体积的相关性[J]. 中国老年学杂志, 2013, 33(14): 3302-3303.
17 蔡玮婷,彭瑜,张钲. 血小板及其趋化因子在动脉粥样硬化中作用的研究进展[J]. 中国循环杂志, 2016, 31(8): 816-818.
18 PikeJ W, ChristakosS. Biology and mechanisms of action of the vitamin D hormone [J]. Endocrinol Metab Clin N Am, 2017, 46(4): 815-843.
19 ChenY, KongJ, SunT, et al. 1,25-Dihydroxyvitamin D(3) suppresses inflammation-induced expression of plasminogen activator inhibitor-1 by blocking nuclear factor-kappaB activation [J]. Arch Biochem Biophys, 2011, 507(2): 241-247.
20 SultanM, TwitoO, TohamiT, et al. Vitamin D diminishes the high platelet aggregation of type 2 diabetes mellitus patients [J]. Platelets, 2019, 30(1): 120-125.
21 Korzonek-SzlachetaI, HudzikB, NowakJ, et al. Mean platelet volume is associated with serum 25-hydroxyvitamin D concentrations in patientswith stable coronary artery disease [J]. Heart Vessels, 2018, 33(11): 1275-1281.
22 NorisP, MelazziniF, BalduiniC L. New roles for mean platelet volume measurement in the clinical practice? [J]. Platelets, 2016, 27(7): 607-612.
23 YildizB S, OzkanE, EsinF, et al. Does high serum uric acid level cause aspirin resistance? [J]. Blood Coagul Fibrinolysis, 2016, 27(4): 412-418.
24 BarbieriL, VerdoiaM, PergoliniP, et al. Uric acid and high-residual platelet reactivity in patients treated with clopidogrel or ticagrelor [J]. Nutr Metab Cardiovasc Dis, 2016, 26(4): 352-358.
25 董海荣,徐肖倩,康德成,等. CP2C19基因多态性与中国北方地区人群缺血性脑卒中氯吡格雷抵抗的相关性研究[J]. 国际检验医学杂志, 2018, 39(7): 820-823.
26 SuJ F, HuX H, LiC Y. Risk factors for clopidogrel resistance in patients with ischemic cerebral infarction and the correlation with ABCB1 gene rs1045642 polymorphism [J]. Exp Ther Med, 2015, 9(1): 267-271.
