Fibrinolysis
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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.
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Physiology
Fibrinolysis.png
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) and urokinase are the agents that convert plasminogen to the active plasmin, thus allowing fibrinolysis to occur. tPA is released into the blood by the healthy endothelium of arterioles in the areas immediately surrounding the clot. tPA and urokinase are themselves inhibited by plasminogen activator inhibitor-1 and plasminogen activator inhibitor-2 (PAI-1 and PAI-2). In contrast, plasmin further stimulates plasmin generation by producing more active forms of both tPA and urokinase.
Alpha 2-antiplasmin and alpha 2-macroglobulin inactivate plasmin. Plasmin activity is also reduced by thrombin-activatable fibrinolysis inhibitor (TAFI), which modifies fibrin to make it less susceptible to plasmin cleavage.
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 thrombin clotting time (TCT) test, which is prolonged in a person who has active 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 therefore used to 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, experimentally in stroke to reperfuse the affected part of the brain, and in massive pulmonary embolism. The process is called thrombolysis.
Antifibrinolytics, such as aminocaproic acid (ε-aminocaproic acid) and tranexamic acid are used as inhibitors of fibrinolysis, which act by blocking the lysine-binding site on plasmin. They are used in menorrhagia and bleeding tendency due to various causes.
Reference
- Cesarman-Maus G, Hajjar KA. Molecular mechanisms of fibrinolysis. Br J Haematol 2005;129:307-21. PMID 15842654.
External link
- Graphical representation (http://www.biocarta.com/pathfiles/h_fibrinolysisPathway.asp) of the fibrinolytic pathway
| Cardiovascular system - Blood |
| Red blood cells - White blood cells - Platelets - Blood plasma |
| White blood cells |
| Granulocytes (Neutrophil granulocytes, Eosinophil granulocytes, Basophil granulocytes) - Lymphocytes - Monocytes |
| Coagulation |
| Coagulation factors: - Fibrin (I) - (Pro)thrombin (II) - FV - FVII - FVIII - FIX - FX - FXI - FXII - FXIII - HMWK - vWF - Tissue factor |
| Inhibitors: Antithrombin - Protein C - Protein S - Protein Z - ZPI - TFPI |
| Fibrinolysis: Plasmin - tPA/urokinase - PAI-1/2 - α2-AP - TAFI |