Plasmin and fibrinolytic serine proteases (PLG/tPA/uPA)

Plasmin is the central effector enzyme of the fibrinolytic system, a serine protease responsible for the degradation of fibrin clots into soluble fragments. It is synthesized in the liver as the inactive zymogen plasminogen and is activated by other serine proteases, primarily tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA) (UniProt P00747, P00750). This system is essential for maintaining vascular patency by balancing the coagulation cascade and preventing excessive thrombus formation. Beyond its role in hemodynamics, the plasminogen system participates in tissue remodeling, wound healing, and pathological processes such as tumor metastasis (Chapin & Hajjar, 2015, Blood Reviews). Therapeutically, this system is targeted in two opposing directions. Thrombolytic agents, such as recombinant tPA (alteplase), are administered to dissolve occlusive thrombi in acute myocardial infarction and ischemic stroke by accelerating plasmin production. In contrast, antifibrinolytic agents like tranexamic acid are used to stabilize clots and reduce blood loss in surgical or traumatic settings by inhibiting plasmin activity (PubChem, Alteplase; PubChem, Tranexamic Acid).

Other names

Plasminogen (PLG)FibrinolysinTissue-type plasminogen activator (tPA)Urokinase-type plasminogen activator (uPA)PLATPLAU

Thrombolytic drugs act as activators that convert the zymogen plasminogen into the active serine protease plasmin, which subsequently cleaves fibrin meshes to dissolve blood clots (StatPearls, Physiology, Fibrinolysis). Antifibrinolytic drugs like tranexamic acid bind to the lysine-binding sites of plasminogen and plasmin, competitively inhibiting their interaction with fibrin and preventing clot degradation (PubChem, Tranexamic Acid).