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Encyclopedia > Fibrinolysis

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. Fibrin is a protein involved in the clotting of blood. ... A thrombus or blood clot is the final product of blood coagulation, through the aggregation of platelets and the activation of the humoral coagulation system. ... The coagulation of blood is a complex process during which blood forms solid clots. ... Ribbon diagram of the enzyme TIM. TIM is catalytically perfect, meaning its conversion rate is limited, or nearly limited to its substrate diffusion rate. ... Plasmin is an important degrading enzyme (EC 3. ... Peptidases (proteases [pronounced pro-tea-aces] and proteolytic enzymes are also commonly used) are enzymes which break peptide bonds of proteins. ... Human kidneys viewed from behind with spine removed The kidneys are bean-shaped excretory organs in vertebrates. ... The liver is the largest internal organ of the human body. ...

Contents


Physiology

Fibrinolysis (simplified). Blue arrows denote stimulation, and red arrows inhibition.
Fibrinolysis (simplified). Blue arrows denote stimulation, and red arrows inhibition.

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. Image File history File links Fibrinolysis. ... Plasmin is an important degrading enzyme (EC 3. ...


Plasminogen contains secondary structure motifs known as kringles, which bind specifically to lysine and arginine residues on fibrin(ogen). When converted from plasminogen into plasmin it functions as a serine protease, cutting specifically C-terminal to these lysine and arginine residues. Fibrin monomers, when polymerized, form protofibrils. These protofibrils contain two strands, anti-parallel, associated non-covalently. 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; further digestion leads to solubilization (Walker & Nesheim 1999). Lysine is one of the 20 amino acids normally found in proteins. ... Arginine (Arg) is an α-amino acid. ... In biochemistry, serine proteases or serine endopeptidases (newer name) are a class of peptidases (enzymes that cleave peptide bonds in proteins) that are characterised by the presence of a serine residue in the active center of the enzyme. ... Factor XIII or fibrin stabilizing factor is an enzyme (EC 2. ...


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. In blood coagulation, tissue plasminogen activator (tPA) is an enzyme (EC 3. ... Urokinase, also called urokinase-type Plasminogen Activator (uPA) is an enzyme (EC 3. ... The endothelium is the layer of thin, flat cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. ... An arteriole is a blood vessel that extends and branches out from an artery and leads to capillaries. ... Plasminogen activator inhibitor-1 is the principal inhibitor of tissue plasminogen activator (tPA) and urokinase (uPA), the activators of plasminogen and hence fibrinolysis (the physiological breakdown of blood clots). ...


Alpha 2-antiplasmin and alpha 2-macroglobulin inactivate plasmin. Plasmin activity is also reduced by thrombin-activable fibrinolysis inhibitor (TAFI), which modifies fibrin to make a less potent cofactor for the tPA-mediated plasminogen activation. Alpha 2-antiplasmin (or α2-antiplasmin or plasmin inhibitor) is a serine protease inhibitor (serpin) responsible for inactivating plasmin, an important enzyme that participates in fibrinolysis and degradation of various other proteins. ... Alpha-2 macroglobulin is a large plasma protein found in the blood. ...


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. D-dimer is a blood test performed in the medical laboratory to diagnose thrombosis. ... It has been suggested that thrombophlebitis be merged into this article or section. ...


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. Metabolic syndrome is a combination of medical disorders that affect a large number of people in a clustered fashion. ...


The fibrinolytic system is closely linked to control of inflammation, and plays a role in disease states associated with inflammation. Plasmin, in addition to lysing fibrin clots, also cleaves the complement system component C3, and fibrin degradation products have some vascular permeability inducing effects. Inflammation is the first response of the immune system to infection or irritation and may be referred to as the innate cascade. ... Plasmin is an important degrading enzyme (EC 3. ... The complement system helps clear pathogens from an organism. ...


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. A myocardial infarction occurs when an atherosclerotic plaque slowly builds up in the inner lining of a coronary artery and then suddenly ruptures, totally occluding the artery and preventing blood flow downstream. ... The coronary circulation consists of the blood vessels that supply blood to, and remove blood from, the heart. ... A stroke or cerebrovascular accident (CVA) occurs when the blood supply to a part of the brain is suddenly interrupted by occlusion (an ischemic stroke- approximately 90% of strokes), by hemorrhage (a hemorrhagic stroke - less than 10% of strokes) or other causes. ... Thrombolysis is the breakdown (lysis) by pharmacological means, of blood clots. ...


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. Aminocaproic acid (marketed as Amicar) is a drug used to treat bleeding disorders. ... Tranexamic acid (commonly marketed as Cyclokapron) is often prescribed for excessive bleeding. ... Lysine is one of the 20 amino acids normally found in proteins. ... Menorrhagia is an abnormally heavy and prolonged menstrual period. ...


References

  • Cesarman-Maus G, Hajjar KA. Molecular mechanisms of fibrinolysis. Br J Haematol 2005;129:307-21. PMID 15842654.
  • Kumar: Robbins and Cotran: Pathologic Basis of Disease, 7th ed., Copyright © 2005 Saunders
  • Walker JB, Nesheim ME. The molecular weights, mass distribution, chain composition, and structure of soluble fibrin degradation products released from a fibrin clot perfused with plasmin. J Biol Chem. 1999;274:5201 - 5212. PMID 9988770.

External link


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

  Results from FactBites:
 
fibrinolysis inhibitor-thrombin topical - [Medication] (963 words)
Fibrinolysis inhibitor and thrombin are agents that are involved in blood clotting.
Fibrinolysis inhibitor-thrombin topical is used to cause blood clotting during surgery or due to trauma when natural blood clotting processes are deficient.
Fibrinolysis inhibitor-thrombin topical is in the FDA pregnancy category C. This means that it is not known whether it will be harmful to an unborn baby.
Primary or secondary fibrinolysis (241 words)
Fibrinolysis leads to the breakdown of fibrin clots (blood clots) and is caused by the action of several enzymes.
Fibrinolysis is a normal body process that occurs continuously to keep naturally-occuring blood clots from growing and causing problems.
Primary fibrinolysis refers to the normal breakdown of clots, whereas secondary fibrinolysis is the breakdown of blood clots and possible abnormal bleeding due to another medical disorder, medications, or other causes.
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