plasminogenplasmin

Plasminogen-plasmin refers to the plasminogen–plasmin system, the principal enzymatic pathway for fibrinolysis, the breakdown of fibrin clots. Plasminogen is a circulating zymogen produced mainly by the liver and found in blood plasma. It binds to fibrin and to cell surfaces via lysine-binding sites, positioning it for activation at sites of clot formation.

Activation of plasminogen is mediated mainly by tissue-type plasminogen activator (tPA), released from endothelial cells, and by urokinase-type plasminogen activator (uPA) from various cells. Cleavage of plasminogen by these activators generates plasmin, a serine protease that cleaves fibrin into soluble degradation products. Plasminogen bound to the clot is preferentially activated, promoting targeted fibrinolysis.

Regulation of the system is tight. Alpha-2 antiplasmin rapidly inhibits free plasmin to limit proteolysis. Plasminogen activator inhibitors, notably PAI-1 and PAI-2, suppress the actions of tPA and uPA. Other inhibitors, such as alpha-2-macroglobulin, can trap plasmin. Dysregulation can contribute to bleeding or thrombotic disorders.

Clinically, congenital plasminogen deficiency is rare but can cause ligneous conjunctivitis and mucosal lesions due to impaired fibrinolysis. In diagnostics, fibrin degradation products, including D-dimer, reflect plasmin activity on crosslinked fibrin and are used to assess fibrinolysis.

Therapeutically, plasminogen activation is harnessed in thrombolytic therapy using tPA (alteplase, reteplase, tenecteplase) to dissolve pathological clots. Antifibrinolytic agents such as tranexamic acid inhibit plasmin formation or activity to reduce bleeding in surgical or traumatic settings. Beyond clot dissolution, plasmin participates in tissue remodeling and inflammatory processes by degrading extracellular matrix components.