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Coagulation

General

Fibrinolysis pathway

Reviewer: Jeremy Parsons, M.D. (see Reviewers page)
Revised: 9 June 2012, last major update June 2012
Copyright: (c) 2002-2012, PathologyOutlines.com, Inc.

General
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● Process of degrading the fibrin clot when it is no longer needed
● Also prevents extension of clot beyond site of injury

tPA and uPA
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● 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
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● 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
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● 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
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Coagulation cascade and fibrinolytic system


The fibrinolytic pathway counterbalances the clotting pathway by breaking down clots. Chart credit to Kendall Crookston, M.D., PhD.

Additional references
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● Arch Pathol Lab Med 2002;126:1376, Clin Lab Med 2009;29:159

End of Coagulation > General > Fibrinolysis pathway

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