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Von Willebrand Factor (vWF) is essential for normal haemostasis involving platelet aggregation induced by high shear forces. In vitro a functional test of platelet aggregation using the filterometer is abnormal in von Willebrand's disease. However in normal people there is no significant correlation between the antigenic assay of vWF and the filter results. To study this discrepancy normal blood before and during venous occlusion, and blood before and after infusion of 1 deamino-(8-D-arginine) vasopressin was studied. During venous occlusion (VO) the increase in vWF due to the release of large multimers correlated precisely with the increase in the filterometer results. That this was due to the plasma vWF and not to any change induced in the platelets was shown as follows: The methodology was altered so that a small amount of the donor's platelet-poor plasma (PPP) was added to homologous normal substrate blood. The effect of the added donor's PPP was then shown to be closely correlated to the increase in the antigenic assay. Analysis of vWF multimer size showed during VO an increase in large multimers. We conclude that the effect of vWF on normal blood may be obscured by variation in platelet aggregability. In the filterometer system as elsewhere the large active multimers probably play a major part in causing platelet adhesion, aggregation and filter blocking. The filterometer test is influenced by the amount of vWF antigen, by the molecular size and activity of the vWF and by platelet sensitivity. Clinically this is a useful global test. 相似文献
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《Platelets》2013,24(2):106-115
Monitoring of platelet ADP receptor P2Y12 inhibition may be performed by a variety of platelet function assays. Given the lack of sensitivity of the existing PFA-100® cartridge formulations to detect P2Y12 inhibition, a new cartridge for the PFA-100 (INNOVANCE® PFA P2Y) has recently been developed. The performance of the new PFA-100 test cartridge was compared with standard collagen/ADP (CADP) and collagen/epinephrine (CEPI) cartridges, light transmission aggregometry, vasodilator-stimulated phosphoprotein, the VerifyNow® P2Y12 assay and multiple electrode aggregometry. In this study, 20 normal blood samples anticoagulated with either citrate or hirudin were spiked with two different clinically relevant concentrations (1 and 10?µM final concentration) of the prasugrel active metabolite (R-138727, Lilly/Daiichi Sankyo) for 30?min at 37°C. Comparison of the platelet function tests demonstrated that all tests (except CADP and CEPI) were substantially inhibited by 10?µM R-138727. Intermediate results were typically obtained with 1?µM R-138727 in citrated blood. However, both MEA ADP and ADPHS tests were highly sensitive to 1?µM R-138727 in hirudin anticoagulated blood. Further comparison of citrate or hirudin blood samples (N?=?5) revealed that all platelet tests (except CEPI) became more sensitive to 1?µM R-138727 in hirudinized blood. The INNOVANCE PFA P2Y cartridge proved to be sensitive to P2Y12 inhibition and was comparable to other currently available platelet function tests. The sensitivity of all platelet function tests for detecting in vitro inhibition of P2Y12 is markedly different depending on the anticoagulant used. 相似文献
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普拉格雷是噻吩吡啶类口服抗血小板药的一个新成员.大鼠单次口服普拉格雷对血小板聚集的抑制作用分别约为噻氯匹定的10倍和氯吡格需的100倍.普拉格雷口服后30 min即可见明显的抗血小板聚集效应并持续72 h,提示其起效迅速H作用持久.普拉格雷与阿司匹林联合应用的抗血小板聚集和抑制血栓形成的作用明显优于单独治疗.在心血管病患者中进行的临床研究证实,普拉格雷的抗血小板效应优于氯吡格雷.因此,普拉格雷是一种高效的抗血小板和抗血栓形成药,有望成为治疗动脉粥样硬化性血栓形成和其他缺血性血管病的有效于段. 相似文献
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Background Clopidogrel is beneficial after acute coronary syndrome. Recent studies suggest the superiority of prasugrel compared with clopidogrel. The enhanced platelet inhibition with prasugrel lead to a reduction in major adverse cardiovascular events in patients with moderate to high risk acute coronary syndrome scheduled for PCI. However, prasugrel showed signs of increased bleeding potential. We performed a meta-analysis to assess clinical safety and efficacy of prasugrel in patients with acute coronary syndrome. Methods We systematically searched PubMed, ISI Web of Knowledge, Cochrane Central Register of Controlled Trials, clinicaltrials. gov, proceedings of major US and European cardiology meetings, China National Knowledge Infrastructure (CNKI) databases 2000-2010 and reviews, reference lists of relevant articles. The search strategy paired the term "prasugrel" "clopidogrel" with the following: "acute coronary syndrome" "percutaneous coronary intervention" We conducted a meta-analysis of randomized double-blind trials that evaluated clinical outcomes in patients with acute coronary syndrome. Two reviewers independently assessed the trials. Differences were resolved by consensus. Results A total of 2 trials with 14512 patients were available for analysis. Overall, prasugrel appeared significantly superior to clopidogrel for the risk of MACE (OR = 0.820.74-0.90, P ﹤0.0001), stent thrombosis (OR = 0.470.35-0.62, P 0.00001), death(OR = 0.850.78-0.93, P = 0.0003), and myocardial infarction (OR = 0.760.68-0.85, P﹤0.00001), without any significant difference in stroke (P = 0.85). However, major bleeding associated with non coronary artery bypass grafting Thrombolysis in Myocardial Infarction related to prasugrel (OR = 1.321.03-1.67, P = 0.03). Conclusions Prasugrel is superior to clopidogrel for acute coronary syndrome, while causing more bleedings. 相似文献
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美国食品药品监督管理局(FDA)于2009年7月9日批准了由美国礼来公司与日本第一三共制药公司共同研
发的噻吩吡啶类新型抗血小板药盐酸普拉格雷(prasugrel hydrochloride,商品名:Effient)上市。盐酸普拉格雷为第
三代抗血小板药, 与第二代抗血小板药氯吡格雷(clopidogrel,Plavix/Iscover)相比,具有作用更快、更强、更持久
、更安全的特点,但其出血问题应引起高度关注,应权衡利弊严格掌握适应症谨慎使用。文中对其药动学、药效学特点及
不良反应等做一介绍。 相似文献
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《Expert opinion on drug discovery》2013,8(7):897-905
Introduction: Prasugrel (CS-747, LY640315) is a third-generation thienopyridine, which gained approval by the FDA in 2009 for its use in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Areas covered: This article focuses on the preclinical profile of prasugrel. Using published preclinical and clinical studies, the authors summarize the pharmacokinetics, pharmacodynamics, and pharmacogenomics of prasugrel and their distinguishing features in efficacy and safety. Expert opinion: Prasugrel has a more rapid, more potent antiplatelet effect with less interindividual response variability when compared to clopidogrel. Those therapeutic advantages are attributed to features of its chemical structure that favor the metabolic conversion of prasugrel to its active metabolite. However, the increased risk of bleeding has been associated with a greater antiplatelet effect and dosing profile; this is especially the case in those patients who are at a higher risk of bleeding complications. It is therefore important for an optimal dosing strategy of prasugrel to be identified to provide a formulation that has the best balance for efficacy and safety. 相似文献