Reviewer: Jeremy Parsons, M.D. (see Reviewers page)
Revised: 9 June 2012, last major update June 2012
Copyright: (c) 2002-2012, PathologyOutlines.com, Inc.
● Process of degrading the fibrin clot when it is no longer needed
● Also prevents extension of clot beyond site of injury
tPA and uPA
● Fibrinolysis initiated by tPA (tissue plasminogen activator) or uPA (urokinase-like plasminogen activator), which convert plasminogen to plasmin in the presence of fibrin by cleaving the Arg561-Val562 peptide bond
● Plasmin degrades the fibrin clot and intact fibrinogen to soluble fibrin/fibrinogen degradation products (FDP)
● Plasmin also inactivates factors Va and VIIIa (as do Protein C and Protein S)
● tPA is produced by endothelial cells; its activation of plasminogen is major mechanism for lysis of fibrin clots
● Recombinant tPA is used to treat myocardial infarction, stroke and some cases of acute thrombosis
● uPA is found in urine and plasma; keeps renal tracts free of blood clots; also is important for other cell surfaces and initiating nonfibrinolytic activities of plasmin
● Excessive fibrinolysis is prevented by plasmin inhibitor (antiplasmin, formerly called alpha2-antiplasmin) and plasminogen activator inhibitor 1 (PAI-1, inhibits tPA and uPA)
● PAI-1 is synthesized by hepatocytes and endothelial cells, is present in platelets and plasma; can bind to fibrin and inhibit plasminogen activators tPA and uPA
● PAI-1 is an acute phase reactant protein, and may increase 30-50 fold over baseline, possibly immediately inactivating systemically administered tPA
● Homozygous deficiency of plasminogen is associated with ligneous conjunctivitis (rare form of chronic pseudomembranous conjunctivitis), and replacement therapy with plasminogen is therapeutic
● Neither heterozygous plasminogen deficiency (0.5 to 2.0% of patients with thrombosis) nor tPA deficiency are associated with increased risk of thrombosis
Coagulation cascade and fibrinolytic system
The fibrinolytic pathway counterbalances the clotting pathway by breaking down clots. Chart credit to Kendall Crookston, M.D., PhD.
● Arch Pathol Lab Med 2002;126:1376, Clin Lab Med 2009;29:159
End of Coagulation > General > Fibrinolysis pathway
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