Fibrinolysis is the process where a fibrin clot, the product of coagulation, is broken down. Its main enzyme, plasmin, cuts the fibrin mesh at various places, leading to the production of circulating fragments that are cleared by other proteinases or by the kidney and liver.
Physiology
Plasmin is produced in an inactive form, plasminogen, in the liver. Although plasminogen cannot cleave fibrin, it still has an affinity for it, and is incorporated into the clot when it is formed.
Tissue plasminogen activator (tPA) is the agent that converts plasminogen to plasmin, thus allowing fibrinolysis to occur. tPA is released into the blood by the healthy endothelium in the areas immediately surrounding the clot. tPA is activated by thrombin (paradoxically the main stimulant of fibrin generation) and Factor XIIa.
tPA cleaves plasminogen, which starts fibrinolysis, though tPA itself is inhibited by other chemicals in the bloodstream. Plasminogen activator inhibitor 1 and 2 (PAI-1 and PAI-2) serve to deactivate tPA.
Alpha-2-antiplasmin degrades plasmin.
Measurement
When plasmin breaks down fibrin, a number of soluble parts are produced. These are called fibrin degradation products (FDPs). FDPs compete with thrombin, and so slow down the conversion of fibrinogen to fibrin (and thus slows down clot formation). This effect can be seen in the TCT or thrombin clotting time test, which is prolonged in a person who has recently undergone fibrinolysis.
FDPs, and a specific FDP, the D-dimer, can be measured using antibody-antigen technology. This is more specific than the TCT, and virtually confirms that fibrinolysis has occurred. It is important to know if fibrinolysis has recently happened, as this can indicate deep vein thrombosis or a pulmonary embolism.
Role in disease
Few disorders of the fibrinolytic system have been documented. Nevertheless, excess levels of PAI and Alpha-2-antiplasmin have been implicated in the metabolic syndrome and various other disease states.
Pharmacology
Fibrinolytic drugs are given after a heart attack to dissolve the thrombus blocking the coronary artery, in stroke to reperfuse the affected part of the brain, and in massive pulmonary embolism. The process is called thrombolysis.
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