Plasmin is the leading enzyme of the fibrinolytic system, a biological process responsible for the dissolution of fibrin clots formed following vascular lesions. These intricate fibrin polymers are designed to create a sort of anti-hemorrhagic plug, which engulfs cells blood (platelets, white blood cells and red blood cells) and various plasma proteins, including the inactive precursor of plasmin, called plasminogen, which has a "high affinity for fibrin molecules. Thanks to this characteristic, plasminogen is concentrated above all in the sites where fibrin is deposited (such as clots).
The plasminogen is converted into plasmin thanks to the intervention of specific natural activators, among which we remember the urokinase (u-PA) and the tissue plasminogen activator (t-PA). Despite the name, the latter is more active at the level circulatory (it is generally secreted very slowly to allow the repair processes of the lesion), while urokinase is more active at the tissue level.Therefore, similarly to what has been seen for coagulation, in fibrinolysis we can distinguish an intrinsic and an extrinsic pathway, both consisting of a series of cascade reactions.
The fibrinolytic system limits the damage deriving from the excessive deposition of fibrin, and the consequent obstruction of the vessels, by abnormal clots (called thrombi).
With a proteolytic mechanism, the newly formed plasmin breaks down fibrin into soluble degradation products. The protease activity of plasmin is similar to that of pancreatic trypsin and is poorly specific (as well as on plasminogen it is also active on other substrates, such as the constituents of plasma complement, coagulation factors V and VIII, fibrinogen and some hormones of a natural proteins, such as ACTH, glucagon and growth hormone). From the proteolysis of fibrinogen and fibrin, peptide fragments of variable size originate, collectively called FDPs (degradation products of fibrinogen and fibrin).
As in the coagulation cascade, specific inhibitors also exist for the proteolytic cascade. In their absence, in fact, an "exaggerated demolition of fibrinogen, fibrin and other proteins important for coagulation would be produced, with the risk of serious bleeding.
During clot formation, plasmin synthesis is generally inhibited by specific substances released by activated platelets and local cells. Only in the presence of fibrin or stasis due to venous occlusion, the endothelium releases an excess quantity of plasminogen activators, which bind to specific receptors resulting in fibrinolysis. While in other body sites the plasmin receptors for the relative inhibitors ( the antiplasmins) are free, at the level of the clot they are engaged by the bond with fibrin; in this way the plasmin is protected from their action and is therefore free to fully carry out its activity.
Some drugs such as streptokinase enhance fibrinolytic activity and as such are useful in the phenomena of hypercoagulability of the blood (thrombosis). On the other hand, there are also antifibrinolytic drugs, particularly useful in patients with hyperfibrinolysis haemorrhages.
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