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血栓形成后综合征的生物标志物:一项病例对照研究。

Biomarkers for post thrombotic syndrome: a case-control study.

作者信息

Bouman A C, Cheung Y W, Spronk H M, Schalkwijk C G, ten Cate H, ten Wolde M, ten Cate-Hoek A J

机构信息

Laboratory for Thrombosis and Hemostasis, Maastricht University Medical Centre, Universiteitssingel 50, Maastricht, the Netherlands; Department of Internal Medicine, Maastricht University Medical Centre, P.Debyelaan 25, Maastricht, the Netherlands.

Department of Internal Medicine, Flevohospital, Hospitaalweg 1, Almere, the Netherlands.

出版信息

Thromb Res. 2014 Aug;134(2):369-75. doi: 10.1016/j.thromres.2014.06.010. Epub 2014 Jun 13.

Abstract

INTRODUCTION

There is limited knowledge on the etiology of post thrombotic syndrome (PTS), although several mechanisms have been proposed. The objectives are to explore the role of different pathogenic mechanisms for PTS, through measurement of an elaborate panel of biomarkers in patients with and without PTS.

MATERIALS AND METHODS

Patients with a history of deep vein thrombosis (DVT) with PTS (cases) and without PTS after minimal 2years follow-up (controls), were selected from the outpatient clinic of two Dutch hospitals. As a reference to the normal population healthy individuals (HI) without a history of venous thromboembolism were invited to participate. The population consisted of: 26 cases, 27 controls, and 26 HI. A panel of predefined biomarkers was measured in venous blood.

RESULTS

D-dimer showed a decreasing trend from cases to controls to HI; p=0.010. Thrombin/antithrombin complex levels were significantly higher in cases than in controls; p=0.032, and HI; p=0.017. APC-ratio was significantly lower in cases compared to controls; p=0.032, and HI; p=0.011. A significant trend of increasing proTAFI from cases, to controls, and HI; p=0.002 was found. There were no differences in inflammatory markers (CRP, Interleukin-6, Interleukin-8). Thrombomodulin, tissue-plasminogen activator, and von Willebrand factor were higher in patients compared to HI. There was a significant trend of decreasing sVCAM, from cases, to controls, and HI; p=0.029.

CONCLUSIONS

Patients with PTS displayed increased coagulation activity, an altered pattern of fibrinolytic marker expression, and increased endothelial activation. We found no evidence of systemic inflammation in patients with PTS at 63months since the last DVT.

摘要

引言

尽管已经提出了几种机制,但关于血栓形成后综合征(PTS)的病因学知识仍然有限。目的是通过测量一组详尽的生物标志物,探讨不同致病机制在有和没有PTS的患者中对PTS的作用。

材料与方法

从两家荷兰医院的门诊中选取有深静脉血栓形成(DVT)病史且患有PTS的患者(病例组)和至少随访2年后无PTS的患者(对照组)。作为正常人群的对照,邀请没有静脉血栓栓塞病史的健康个体(HI)参与。研究人群包括:26例病例、27例对照和26例HI。在静脉血中测量一组预先定义的生物标志物。

结果

D-二聚体从病例组到对照组再到HI呈现下降趋势;p = 0.010。凝血酶/抗凝血酶复合物水平在病例组中显著高于对照组;p = 0.032,与HI相比;p = 0.017。与对照组相比,病例组的活化蛋白C比值显著降低;p = 0.032,与HI相比;p = 0.011。从病例组到对照组再到HI,发现前激肽释放酶激活因子有显著增加趋势;p = 0.002。炎症标志物(CRP、白细胞介素-6、白细胞介素-8)没有差异。与HI相比,患者的血栓调节蛋白、组织纤溶酶原激活剂和血管性血友病因子更高。从病例组到对照组再到HI,可溶性血管细胞黏附分子有显著下降趋势;p = 0.029。

结论

PTS患者表现出凝血活性增加、纤溶标志物表达模式改变以及内皮激活增加。在最后一次DVT发生63个月后,我们没有发现PTS患者存在全身炎症的证据。

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