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改善静脉血栓栓塞症中的纤维蛋白溶解:纤维蛋白结构的影响。

Improving fibrinolysis in venous thromboembolism: impact of fibrin structure.

机构信息

a Institute of Cardiology, Jagiellonian University Medical College , Kraków , Poland.

出版信息

Expert Rev Hematol. 2019 Aug;12(8):597-607. doi: 10.1080/17474086.2019.1627193. Epub 2019 Jul 5.

Abstract

. Fibrinolysis is of key importance in maintaining vessel patency. Impaired fibrinolysis associated with more compact fibrin structure has been shown in patients with venous thromboembolism (VTE), including deep-vein thrombosis and pulmonary embolism (PE). Currently, recombinant or modified plasminogen activators are the only commonly available thrombolytic agents. However, they are fraught with side effects and suboptimal effectiveness. . Based on the available literature, the current evidence linking fibrinolysis with VTE and potential therapeutic targets among fibrinolysis proteins are presented. . Prolonged clot lysis time has been reported as a new predictor of first-time and recurrent VTE, including PE. Anticoagulant therapy, including non-vitamin K antagonist oral anticoagulants, has a favorable impact on fibrinolysis in VTE patients. Several VTE risk factors are also related to lower efficiency of fibrinolysis and their treatment improve fibrinolysis, in part by alterations to fibrin properties. There is an increasing number of studies aiming at developing novel profibrinolytic therapeutic agents for treatment of VTE patients, mostly targeting the antifibrinolytic proteins, i.e. antiplasmin, plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor.

摘要

纤溶对于维持血管通畅至关重要。静脉血栓栓塞症(VTE)患者,包括深静脉血栓形成和肺栓塞(PE),其纤溶功能受损,与纤维蛋白结构更加紧密有关。目前,重组或修饰的纤溶酶原激活剂是唯一常用的溶栓药物。然而,它们存在副作用和效果不佳的问题。基于现有文献,本文介绍了纤溶与 VTE 的关联以及纤溶蛋白中的潜在治疗靶点。研究表明,较长的血栓溶解时间是首次和复发性 VTE(包括 PE)的新预测指标。抗凝治疗,包括非维生素 K 拮抗剂口服抗凝剂,对 VTE 患者的纤溶有积极影响。一些 VTE 的危险因素也与纤溶效率降低有关,其治疗方法可以改善纤溶,部分原因是纤维蛋白特性的改变。目前,越来越多的研究旨在开发新型纤溶治疗药物,以治疗 VTE 患者,主要针对抗纤维蛋白溶解蛋白,即抗纤溶酶、纤溶酶原激活物抑制剂-1 和凝血酶激活的纤溶抑制物。

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