Biology, embryology, histopathology, and pathology of the tissues that constitute multicellular organisms.

fibrinolytic system

The fibrinolytic system dissolves fibrin blood clots, acting in reverse to the coagulation system.

ε-aminocaproic acid : antifibrinolytics : fibrin clots : fibrin degradation products : fibrinolysis : kringle domains : PAI-1, PAI-2 : plasmin : plasminogen : plasminogen activator inhibitors : serine proteases : serpins : thrombolytic agents : tissue plasminogen activator (PLAT, tPA) : tranexamic acid : uPA : urokinase : urokinase receptor : zymogen

Plasminogen, the inactive, zymogen form of plasmin, is incorporated into fibrin clots as they form. Cleavage of plasminogen by tissue plasminogen activator (PLAT, tPA) and urokinase converts plasminogen to the active serine protease plasmin form. Acting as a serine protease, the kringle domains of plasmin bind to arginine and lysine residues and cleave fibrin into fibrin degradation products (fibrinolysis).

Tissue plasminogen activator (PLAT, tPA) is a serine protease secreted by cells of the arteriolar endothelium. Urokinase, also termed urokinase-type plasminogen activator (uPA), is also a serine protease that contains a serine protease domain, a kringle domain, and a growth factor domain. The serpins, plasminogen activator inhibitor-1 (PAI-1) and plasminogen activator inhibitor-2 (PAI-2) irreversibly inhibit the protease (peptidase) activity of tPA and uPA.

In the extracellular matrix, urokinase binds to the urokinase receptor, tethering urokinase to the cell membrane. Through its interaction with the urokinase receptor, urokinase participates in cell adhesion, migration, and cellular mitotic pathways. It appears that tissue degradation following plasminogen activation facilitates tissue invasion and contributes to establishment of tumor metastasis, making urokinase an attractive potential target for anticancer inhibitors. Urokinase is employed as a thrombolytic agent in the treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE). Both urokinase and recombinant tissue plasminogen activator (PLAT, tPA) are employed in treatment of myocardial infarction (MI), and recombinant PLAT is used in treatment of acute stroke (CVA, cerebrovascular accident).

Conversely, antifibrinolytics, such as aminocaproic acid (ε-aminocaproic acid) and the more potent tranexamic acid are employed as inhibitors of fibrinolysis. They act by blocking the lysine-binding site in the kringle domains on plasminogen, and are employed in treatment of menorrhagia, excessive post-operative bleeding, and bleeding dyscrasias.