Fibrinolysis and the control of blood coagulation

Abstract

Fibrin plays an essential role in hemostasis as both the primary product of the coagulation cascade and the ultimate substrate for fibrinolysis. Fibrinolysis efficiency is greatly influenced by clot structure, fibrinogen isoforms and polymorphisms, the rate of thrombin generation, the reactivity of thrombus-associated cells such as platelets, and the overall biochemical environment. Regulation of the fibrinolytic system, like that of the coagulation cascade, is accomplished by a wide array of cofactors, receptors, and inhibitors. Fibrinolytic activity can be generated either on the surface of a fibrin-containing thrombus, or on cells that express profibrinolytic receptors. In a widening spectrum of clinical disorders, acquired and congenital defects in fibrinolysis contribute to disease morbidity, and new assays of global fibrinolysis now have potential predictive value in multiple clinical settings. Here, we summarize the basic elements of the fibrinolytic system, points of interaction with the coagulation pathway, and some recent clinical advances.

Keywords: Coagulation; Fibrin(ogen); Fibrinolysis; Hemostasis; Thrombosis.

Fig. 1

Human acute promyelocytic leukemia (APL) cells overexpress annexin A2. Formalin-fixed APL cells cultured from a human bone marrow aspirate were stained with either rabbit polyclonal IgG directed against annexin A2 (A) or pre-immune IgG (B). Primary antibody binding was detected with fluorescein isothiocyanate-labeled goat anti-rabbit IgG (green). Nuclei were counterstained with propidium iodide (red). Original magnification 100×.