Preferred Label : Fibrinolysis Pathway;
Alternative definition : BIOCARTA: Clot formation and fibrinolysis is a balance of plasmin activation/inhibition
and thrombin-thrombomodulin activity that regulates fibrin polymer formation and degradation.
Active thrombin is produced by the cleavage of prothrombin in the intrinsic thrombin
activation pathway or the extrinsic thrombin activation pathway. Cleavage of fibrinogen
by thrombin releases the fibrin monomers that auto-polymerize within seconds into
fibrin threads or fibers. The coagulation cascade has many feedback loops. One example
is the binding of thrombin to the fibrin polymers resulting in a reduction in soluble
thrombin. The fibers form a more stable clot as a result of the covalent bonds formed
by activated factor XIII enzyme (also known as Fibrin-stabilizing factor). These fibers
form a mesh that traps platelets, blood cells and plasma to form a clot. The removal
of the clot is caused by plasmin cleavage of the fibrin monomers into soluble fibrin
degradation products. Plasmin is formed by the cleavage of plasminogen between Arg561
and Val562. Plasmin is a two-chain trypsin-like serine protease. Plasminogen activator
inhibitor 1 (PAI1) and plasminogen activator inhibitor 2 (PAI2) inhibit cleavage of
plasminogen by tissue-type plasminogen activator (tPA) or urokinase plasminogen activator
(uPA). The presence of fibrin fibers and fibrin degradation products [(DD)E1 and (DD)E2]
exert a two-fold stimulation of tPA and uPA. Plasmin activity is also inhibited by
alpha2-antiplasmin. Thrombin activatable fibrinolysis inhibitor (TAFI) is a carboxypeptidase
B-like proenzyme activated by the thrombin-thrombomodulin dimer. TAFI cleaves (DD)E2
to separate DD and E fragments which do not enhance the activation of tPA or uPA and
results in a reduced feedback signal. Overabundance or increased activity of the plasminogen
activator inhibitors or reduced presence or function of tPA or uPA can result in atherosclerotic
disease and venous thrombosis due to an increase in fibrin deposition or formation
of a thrombus. Thrombosis can also result from plasminogen deficiency caused by a
lack of protein or lack of functional protein. Reduced or depleted levels of alpha2-antiplamin
can result in severe bleeding disorders. (This definition may be outdated - see the
DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_fibrinolysisPathway;
Origin ID : C39080;
UMLS CUI : C1517172;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
