Coagulation
General
Fibrinolysis pathway

Author: Jeremy Parsons, M.D. (see Authors page)

Revised: 29 February 2016, last major update June 2012

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

PubMed Search: Fibrinolysis pathway
Definition / General
  • Process of degrading the fibrin clot when it is no longer needed
  • Also prevents extension of clot beyond site of injury
Interpretation
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
  • 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

Deficiency conditions
  • 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
Diagrams / Tables

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Coagulation cascade, fibrinolytic system



Flickr image courtesy of Kendall Crookston, M.D., Ph.D.:

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Counterbalance of clotting pathway