Molecular mechanisms and clinical significance of fibrinolysis

Abstract

Fibrinolysis is the process of proteolytic digestion of fibrin aimed in vivo at dissolving clots or thrombi to restore the blood flow. In blood, the fibrinolytic system comprises a network of interrelated biochemical reactions that occur predominantly on the surface of fibrin fibers, the structural scaffold of hemostatic clots and obstructive thrombi. This review provides a brief description of the fibrinolytic system components and of the most important fibrinolytic reactions, including their modulation. The central enzyme in fibrinolysis is plasmin, a serine protease formed from its inactive precursor, plasminogen, upon the action of proteins and enzymes, whose formation and/or activation is triggered by various pathological stimuli. Plasmin cleaves a variety of substrates other than fibrin and therefore is involved in a number of biological processes other than hemostasis and thrombosis. There are several mechanisms moderating the activity of fibrinolytic enzymes that may become altered in various diseases. When the ratio of blood pro-and antifibrinolytic compounds is altered, hyper-or hypofibrinolysis might develop that causes and/or exacerbates hemorrhage or thrombosis, respectively. The paper contains an original pathogenic classification of fibrinolytic disorders and describes mechanisms of the primary and secondary hypo-and hyperfibrinolysis in various pathological conditions. Diagnosis of fibrinolytic defects builds on clinical symptoms along with defining the time of serum clots dissolving in vitro and serum levels of molecular markers. The principles of laboratory diagnostics of pathological fibrinolysis, based on the comprehension of the molecular mechanisms of normal and impaired fibrinolytic reactions, are reviewed. Treatment of pathological fibrinolysis implies the correction of either hyper-or hypofibrinolytic conditions and, therefore, is based on the administration of either antifibrinolytics (ε-eminocaproic and tranexamic acids) or thrombolytics (mainly, plasminogen activators) in combination with other therapies against bleeding and thrombosis.

Keywords

fibrin / thrombosis / fibrinolysis / plasminogen / plasmin / thrombolytics

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Litvinov R.I.