Synapse Research Institute, 6217 KD Maastricht, The Netherlands.
Department of Pathology and Laboratory Medicine and UNC Blood Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Int J Mol Sci. 2021 Mar 9;22(5):2758. doi: 10.3390/ijms22052758.
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.
纤维蛋白溶解是止血过程中的一个重要过程，负责在伤口愈合过程中溶解血栓。纤溶酶是这一过程中的核心酶，能够裂解纤维蛋白。直到最近开发出定量这些指标的检测方法，纤维蛋白溶解过程中纤溶酶的产生（PG）和抑制的动力学才得到充分理解。纤溶酶动力学的评估可识别纤维蛋白溶解功能障碍，并更好地理解异常纤维蛋白溶解与疾病发病机制之间的关系。此外，直接测量抗纤维蛋白溶解药物（如氨甲环酸）对 PG 的抑制作用，可作为评估抗纤维蛋白溶解治疗在出血性疾病中的风险和有效性的有用工具。本文综述了现有的 PG 检测方法，这些方法可直接测量人血浆和鼠血浆中纤溶酶形成和抑制的动力学，并重点介绍了它们在确定纤溶酶在包括血管性水肿、血友病、罕见出血性疾病、COVID-19 或饮食诱导肥胖等疾病中的作用方面的应用。此外，本文还介绍了 PG 检测方法作为一种有前途的临床和研究方法，可用于监测抗纤维蛋白溶解药物并筛选遗传或获得性纤维蛋白溶解障碍。
