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达比加群对血小板功能和纤维蛋白溶解的影响。

Impact of dabigatran on platelet function and fibrinolysis.

作者信息

Tsantes Argirios E, Kyriakou Elias, Bonovas Stefanos, Chondrogianni Maria, Zompola Christina, Liantinioti Chrissoula, Simitsi Athina, Katsanos Aristeidis H, Atta Maria, Ikonomidis Ignatios, Kapsimali Violetta, Kopterides Petros, Tsivgoulis Georgios

机构信息

Laboratory of Haematology & Blood Bank Unit, "Attikon" University Hospital, School of Medicine, University of Athens, Athens, Greece.

Department of Pharmacology, School of Medicine, University of Athens, Athens, Greece.

出版信息

J Neurol Sci. 2015 Oct 15;357(1-2):204-8. doi: 10.1016/j.jns.2015.07.031. Epub 2015 Jul 23.

Abstract

BACKGROUND

We sought to evaluate the potential enhanced fibrinolytic and antiplatelet activity of dabigatran etexilate (DE) due to decreased thrombin levels in patients with stroke or transient ischemic attack and non-valvular atrial fibrillation (NVAF).

METHODS

Consecutive patients with cerebrovascular diseases and NVAF that were treated with DE in a tertiary university hospital. Fibrinolysis and platelet function were assessed by thromboelastometry (ROTEM) and platelet function analyzer (PFA)-100, respectively, before and after treatment with DE. Conventional coagulation tests, endogenous thrombin potential (ETP) and hemoclot thrombin inhibitors (HTI), were also performed in order to detect any possible correlation between dabigatran plasma levels, its anticoagulant activity and the intensity of platelet dysfunction or fibrinolysis.

RESULTS

A total of nineteen patients fulfilled our inclusion criteria (mean age 62.3±7.2years; 47% males; median CHADS2-score: 3; interquartile range: 2-4). DE treatment was associated with a significant reduction of the lysis index (LI60) at 60min (p=0.036), and prolongation of the PFA-100 CEPI closure time (p=0.024). After dabigatran treatment, abnormal PFA-100 results were obtained in two patients (11%, 95% CI: 2%-33%). DE levels (determined by HTI) were strongly inversely correlated (rho=-0.85; p<0.001) with the area under the curve (AUC) values in ETP assay. Νo association was found between HTI and PFA-100 CEPI CT (p=0.64), or LI60 measurements (p=0.60).

CONCLUSIONS

Our findings indicate that DE might affect platelet function and fibrinolysis and highlight the potential role of ETP as an alternative option in DE monitoring. The intensity and clinical relevance of DE antiplatelet and fibrinolytic effects require further investigation.

摘要

背景

我们试图评估在患有中风或短暂性脑缺血发作及非瓣膜性心房颤动(NVAF)的患者中,由于凝血酶水平降低,达比加群酯(DE)潜在增强的纤溶和抗血小板活性。

方法

在一家三级大学医院中,对连续接受DE治疗的脑血管疾病和NVAF患者进行研究。分别在DE治疗前后,通过血栓弹力图(ROTEM)和血小板功能分析仪(PFA)-100评估纤溶和血小板功能。还进行了传统凝血试验、内源性凝血酶潜力(ETP)和血凝块凝血酶抑制剂(HTI)检测,以检测达比加群血浆水平、其抗凝活性与血小板功能障碍或纤溶强度之间的任何可能相关性。

结果

共有19名患者符合纳入标准(平均年龄62.3±7.2岁;47%为男性;CHADS2评分中位数:3;四分位间距:2 - 4)。DE治疗与60分钟时溶解指数(LI60)显著降低(p = 0.036)以及PFA-100 CEPI封闭时间延长(p = 0.024)相关。达比加群治疗后,两名患者(11%,95%置信区间:2% - 33%)的PFA-100结果异常。HTI测定的DE水平与ETP测定中的曲线下面积(AUC)值呈强烈负相关(rho = -0.85;p < 0.001)。未发现HTI与PFA-100 CEPI CT(p = 0.64)或LI60测量值(p = 0.60)之间存在关联。

结论

我们的研究结果表明,DE可能影响血小板功能和纤溶,并突出了ETP作为DE监测替代选项的潜在作用。DE抗血小板和纤溶作用的强度及临床相关性需要进一步研究。

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