The fibrinolytic system has evolved to dissolve intravascular thrombus and vessel-sealing clot after control of the vascular breach. The system prevents inappropriate accumulation and extension of fibrin. It is important in the repair and remodeling process following injury.

The major fibrinolytic enzyme is plasmin, which circulates as its inert proenzyme plasminogen. The conversion of plasminogen to plasmin is facilitated by the plasminogen activators, thrombin, fibrin, and factor XII (Hageman factor). Tissue-type plasminogen activator (tPA) is produced predominantly in the vascular endothelium in the presence of fibrin, while the urokinaselike plasminogen is found in urine and other secretions. The proteolytic function of tPA is inhibited by plasminogen activator inhibitor (PAI), which is produced by the vascular endothelium (PAI-1) or the placenta (PAI-2).

Plasmin can be inactivated by the serine protease inhibitor alpha 2-antiplasmin and by alpha 2-macroglobulin, a large plasma protein produced by the liver that is found in increased concentration in nephrotic syndrome. Alpha 2-antiplasmin deficiency can lead to a bleeding tendency.

Plasmin functions as a serine protease, cutting specifically C-terminal to the lysine and arginine residues on fibrin. Fibrin monomers, when polymerized, form protofibrils. These protofibrils contain two strands, antiparallel, associated noncovalently. Within a single strand, the fibrin monomers are covalently linked through the actions of coagulation factor XIII. Thus, plasmin action on a clot initially creates nicks in the fibrin, and further digestion leads to solubilization. These soluble parts, called fibrin degradation products, compete with thrombin and slow down the conversion of fibrinogen to fibrin. This effect can be seen in the thrombin clotting time test, which is prolonged in a person who has active fibrinolysis. Soluble fibrin degradation products are cleared by the reticuloendothelial system.

Antifibrinolytic agents (aprotinin, epsilon-aminocaproic acid [EACA], and tranexamic acid) can reduce the amount of blood loss and the need for blood transfusions.

Tranexamic acid (Cyklokapron) and EACA (Amicar) are antifibrinolytic amino acids with the ability to bind to plasminogen by its lysine-binding site, preventing its association with fibrin. They also inhibit the proteolytic activity of plasmin. Tranexamic acid is more potent but less well absorbed orally than EACA. Both drugs are minimally metabolized and are mainly excreted unchanged in the urine, with plasma half-time of 2 to 10 hours. Dosage reduction is indicated in renal impairment.