Antiplatelet therapy with aspirin or clopidogrel or both is the standard care for patients with proven coronary or peripheral arterial disease,especially those undergoing endovascular revascularization procedures. How...Antiplatelet therapy with aspirin or clopidogrel or both is the standard care for patients with proven coronary or peripheral arterial disease,especially those undergoing endovascular revascularization procedures. However,despite the administration of the antiplatelet regiments,some patients still experience recurrent cardiovascular ischemic events. So far,it is well documented by several studies that in vitro response of platelets may be extremely variable. Poor antiplatelet effect of clopidogrel or high on-treatment platelet reactivity(HTPR) is under investigation by numerous recent studies. This review article focuses on methods used for the ex vivo evaluation of HTPR,as well as on the possible underlying mechanisms and the clinical consequences of this entity. Alternative therapeutic options and future directions are also addressed.展开更多
AIM: To optimize the experimental protocols for a simple, sensitive and accurate bleeding assay.METHODS: Bleeding assay was performed in mice by tail tip amputation, immersing the tail in saline at 37 ℃, continuously...AIM: To optimize the experimental protocols for a simple, sensitive and accurate bleeding assay.METHODS: Bleeding assay was performed in mice by tail tip amputation, immersing the tail in saline at 37 ℃, continuously monitoring bleeding patterns and measuring bleeding volume from changes in the body weight. Sensitivity and extent of variation of bleeding time and bleeding volume were compared in mice treated with the P2 Y receptor inhibitor prasugrel at various doses or in mice deficient of Fc Rγ, a signaling protein of the glycoprotein VI receptor.RESULTS: We described details of the bleeding assay with the aim of standardizing this commonly used assay. The bleeding assay detailed here was simple to operate and permitted continuous monitoring of bleedingpattern and detection of re-bleeding. We also reported a simple and accurate way of quantifying bleeding volume from changes in the body weight, which correlated well with chemical assay of hemoglobin levels(r2 = 0.990, P < 0.0001). We determined by tail bleeding assay the dose-effect relation of the anti-platelet drug prasugrel from 0.015 to 5 mg/kg. Our results showed that the correlation of bleeding time and volume was unsatisfactory and that compared with the bleeding time, bleeding volume was more sensitive in detecting a partial inhibition of platelet's haemostatic activity(P < 0.01). Similarly, in mice with genetic disruption of Fc Rγ as a signaling molecule of P-selectin glycoprotein ligand-1 leading to platelet dysfunction, both increased bleeding volume and repeated bleeding pattern defined the phenotype of the knockout mice better than that of a prolonged bleeding time.CONCLUSION: Determination of bleeding pattern and bleeding volume, in addition to bleeding time, improved the sensitivity and accuracy of this assay, particularly when platelet function is partially inhibited.展开更多
目的:系统评价替格瑞洛对比普拉格雷对血小板反应性的影响,以为临床治疗提供循证参考。方法:计算机检索Pub Med、中国期刊全文数据库和万方数据库,收集替格瑞洛对比普拉格雷对血小板反应性影响的随机对照试验(RCT)和对照试验,对符合纳...目的:系统评价替格瑞洛对比普拉格雷对血小板反应性的影响,以为临床治疗提供循证参考。方法:计算机检索Pub Med、中国期刊全文数据库和万方数据库,收集替格瑞洛对比普拉格雷对血小板反应性影响的随机对照试验(RCT)和对照试验,对符合纳入标准的临床研究进行资料提取,并采用Cochrane系统评价员手册5.1.0进行质量评价,再采用Rev man 5.1统计软件进行Meta分析。结果:共纳入17项RCT,合计2 757例患者。Meta分析结果显示,负荷剂量下,无论采用Verify Now P2Y12(VN)检测法[MD=15.43,95%CI(-0.39,31.25),P=0.06]或血管扩张刺激磷酸蛋白(VASP)检测法[MD=-3.04,95%CI(-8.98,2.90),P=0.32],替格瑞洛与普拉格雷对血小板反应性的效果相当,两组比较差异均无统计学意义;维持剂量下,无论采用VN检测法[MD=-48.94,95%CI(-58.04,-39.84),P<0.001]或VASP检测法[MD=-14.32,95%CI(-20.45,-8.20),P<0.001],替格瑞洛对血小板反应性的效果均优于普拉格雷,两组比较差异均有统计学意义。结论:在初期负荷剂量使用抗血小板药物时,选用替格瑞洛或普拉格雷对血小板反应性的影响没有显著差异,而后期维持剂量使用抗血小板药物时,替格瑞洛对血小板反应性的效果优于普拉格雷。展开更多
文摘Antiplatelet therapy with aspirin or clopidogrel or both is the standard care for patients with proven coronary or peripheral arterial disease,especially those undergoing endovascular revascularization procedures. However,despite the administration of the antiplatelet regiments,some patients still experience recurrent cardiovascular ischemic events. So far,it is well documented by several studies that in vitro response of platelets may be extremely variable. Poor antiplatelet effect of clopidogrel or high on-treatment platelet reactivity(HTPR) is under investigation by numerous recent studies. This review article focuses on methods used for the ex vivo evaluation of HTPR,as well as on the possible underlying mechanisms and the clinical consequences of this entity. Alternative therapeutic options and future directions are also addressed.
基金Supported by Project and Fellowship Grants from the National Health and Medical Research Council of Australia
文摘AIM: To optimize the experimental protocols for a simple, sensitive and accurate bleeding assay.METHODS: Bleeding assay was performed in mice by tail tip amputation, immersing the tail in saline at 37 ℃, continuously monitoring bleeding patterns and measuring bleeding volume from changes in the body weight. Sensitivity and extent of variation of bleeding time and bleeding volume were compared in mice treated with the P2 Y receptor inhibitor prasugrel at various doses or in mice deficient of Fc Rγ, a signaling protein of the glycoprotein VI receptor.RESULTS: We described details of the bleeding assay with the aim of standardizing this commonly used assay. The bleeding assay detailed here was simple to operate and permitted continuous monitoring of bleedingpattern and detection of re-bleeding. We also reported a simple and accurate way of quantifying bleeding volume from changes in the body weight, which correlated well with chemical assay of hemoglobin levels(r2 = 0.990, P < 0.0001). We determined by tail bleeding assay the dose-effect relation of the anti-platelet drug prasugrel from 0.015 to 5 mg/kg. Our results showed that the correlation of bleeding time and volume was unsatisfactory and that compared with the bleeding time, bleeding volume was more sensitive in detecting a partial inhibition of platelet's haemostatic activity(P < 0.01). Similarly, in mice with genetic disruption of Fc Rγ as a signaling molecule of P-selectin glycoprotein ligand-1 leading to platelet dysfunction, both increased bleeding volume and repeated bleeding pattern defined the phenotype of the knockout mice better than that of a prolonged bleeding time.CONCLUSION: Determination of bleeding pattern and bleeding volume, in addition to bleeding time, improved the sensitivity and accuracy of this assay, particularly when platelet function is partially inhibited.
文摘目的:系统评价替格瑞洛对比普拉格雷对血小板反应性的影响,以为临床治疗提供循证参考。方法:计算机检索Pub Med、中国期刊全文数据库和万方数据库,收集替格瑞洛对比普拉格雷对血小板反应性影响的随机对照试验(RCT)和对照试验,对符合纳入标准的临床研究进行资料提取,并采用Cochrane系统评价员手册5.1.0进行质量评价,再采用Rev man 5.1统计软件进行Meta分析。结果:共纳入17项RCT,合计2 757例患者。Meta分析结果显示,负荷剂量下,无论采用Verify Now P2Y12(VN)检测法[MD=15.43,95%CI(-0.39,31.25),P=0.06]或血管扩张刺激磷酸蛋白(VASP)检测法[MD=-3.04,95%CI(-8.98,2.90),P=0.32],替格瑞洛与普拉格雷对血小板反应性的效果相当,两组比较差异均无统计学意义;维持剂量下,无论采用VN检测法[MD=-48.94,95%CI(-58.04,-39.84),P<0.001]或VASP检测法[MD=-14.32,95%CI(-20.45,-8.20),P<0.001],替格瑞洛对血小板反应性的效果均优于普拉格雷,两组比较差异均有统计学意义。结论:在初期负荷剂量使用抗血小板药物时,选用替格瑞洛或普拉格雷对血小板反应性的影响没有显著差异,而后期维持剂量使用抗血小板药物时,替格瑞洛对血小板反应性的效果优于普拉格雷。
