plasmininhibitor

Plasmin inhibitor refers to any protein that restrains plasmin, the serine protease responsible for fibrin degradation in the fibrinolytic system. Plasmin is generated from plasminogen mainly by tissue plasminogen activator (tPA) or urokinase-type plasminogen activator (uPA), and its activity is tightly regulated to balance clot breakdown with hemostasis.

The principal direct plasmin inhibitor in blood is alpha-2-antiplasmin (α2-antiplasmin). This serpin rapidly forms a 1:1 complex with plasmin, inactivating its proteolytic activity and preventing excessive fibrin breakdown. Other inhibitors, such as alpha-1-antitrypsin, can inhibit plasmin of lower potency, and alpha-2-macroglobulin can trap plasmin through a broad protease-inhibitor mechanism.

In addition to direct inhibitors, there are inhibitors that regulate plasmin generation by blocking plasminogen activation. Plasminogen activator inhibitors, notably PAI-1 and PAI-2, inhibit tissue plasminogen activator (tPA) and urokinase (uPA), thereby reducing conversion of plasminogen to plasmin. PAI-1 is abundant in plasma and endothelium, while PAI-2 is expressed in certain tissues and can be upregulated in response to stress.

Clinical relevance is rooted in the balance between coagulation and fibrinolysis. Deficiency of α2-antiplasmin can lead to excessive fibrinolysis and bleeding; elevated levels of PAI-1 or PAI-2 can predispose to thrombosis by limiting clot breakdown. Antifibrinolytic drugs such as tranexamic acid and aminocaproic acid inhibit plasmin activity and are used to treat bleeding conditions where fibrinolysis is excessive.

Overall, plasmin inhibitors play a crucial role in maintaining hemostatic balance by restraining plasmin activity and limiting plasmin generation.