Assessing Plasmin Generation in Health and Disease.

Assessing Plasmin Generation in Health and Disease.
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DOI:
10.3390/ijms22052758
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发表时间:
2021-03-09
影响因子:
5.6
通讯作者:
de Laat B
de Laat B
中科院分区:
生物学2区
文献类型:
--
作者:
Miszta A;Huskens D;Donkervoort D;Roberts MJM;Wolberg AS;de Laat B

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纤溶是止血的重要过程,负责在伤口愈合过程中溶解凝块。纤溶酶通过其分解纤维蛋白的能力是这一过程中的中心酶。纤溶过程中纤溶酶的生成(PG)和抑制的动力学一直知之甚少,直到最近定量这些指标的分析方法的发展。对纤溶酶动力学的评估可以识别纤溶功能障碍,并更好地了解异常纤维蛋白溶解与疾病发病机制之间的关系。此外,直接测量氨甲环酸等抗纤溶药物对PG的抑制作用,可作为评估出血性疾病抗纤溶治疗的风险和有效性的有用工具。本文综述了可用于直接测定人和小鼠血浆中纤溶酶形成和抑制动力学的PG分析方法,并重点介绍了它们在确定纤溶酶在各种疾病中的作用方面的应用,这些疾病包括血管水肿、血友病、罕见出血性疾病、新冠肺炎或饮食诱导的肥胖。此外,本文还介绍了PG试验作为监测抗纤溶药物和筛选遗传性或获得性纤溶疾病的一种有前景的临床和研究方法。
Fibrinolysis is an important process in hemostasis responsible for dissolving the clot during wound healing. Plasmin is a central enzyme in this process via its capacity to cleave fibrin. The kinetics of plasmin generation (PG) and inhibition during fibrinolysis have been poorly understood until the recent development of assays to quantify these metrics. The assessment of plasmin kinetics allows for the identification of fibrinolytic dysfunction and better understanding of the relationships between abnormal fibrin dissolution and disease pathogenesis. Additionally, direct measurement of the inhibition of PG by antifibrinolytic medications, such as tranexamic acid, can be a useful tool to assess the risks and effectiveness of antifibrinolytic therapy in hemorrhagic diseases. This review provides an overview of available PG assays to directly measure the kinetics of plasmin formation and inhibition in human and mouse plasmas and focuses on their applications in defining the role of plasmin in diseases, including angioedema, hemophilia, rare bleeding disorders, COVID-19, or diet-induced obesity. Moreover, this review introduces the PG assay as a promising clinical and research method to monitor antifibrinolytic medications and screen for genetic or acquired fibrinolytic disorders.
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