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Measurement of Factor V Activity in Human Plasma Using a Microplate Coagulation Assay
Published on: September 9, 2012
Modulation of fibrin cofactor activity in plasminogen activation
1Department of Biochemistry, Queen's University, Kingston, Ontario, Canada, K7L 3N6. nesheimm@post.queensu.ca
Annals of the New York Academy of Sciences
|July 20, 2001
Summary
Thrombin activatable fibrinolysis inhibitor (TAFI) links coagulation and fibrinolysis. Activated TAFI (TAFIa) suppresses fibrinolysis by downregulating tissue plasminogen activator cofactor activity, impacting clot breakdown.
Area of Science:
- Biochemistry
- Molecular Biology
- Hematology
Background:
- Fibrin serves as a cofactor for plasminogen activation by tissue plasminogen activator (tPA).
- Plasmin-mediated fibrin cleavage initially enhances fibrin's cofactor activity by exposing lysine residues.
- Thrombin activatable fibrinolysis inhibitor (TAFI) is a carboxypeptidase B-like enzyme generated during fibrin formation.
Purpose of the Study:
- To investigate the role of TAFI in regulating fibrinolysis.
- To elucidate the mechanism by which TAFI influences the interaction between fibrin, plasminogen, and tPA.
Main Methods:
- Enzyme assays to measure plasminogen activation.
- Analysis of fibrin degradation products.
- Biochemical characterization of TAFI and TAFIa activity.
Main Results:
- TAFI activation by thrombin generates TAFIa, which downregulates tPA cofactor activity.
- TAFIa eliminates the upregulation of fibrin's cofactor activity caused by initial plasmin cleavage.
- Fibrin degradation products retain significant tPA cofactor activity, which is strongly inhibited by TAFIa.
Conclusions:
- TAFI acts as a crucial link between coagulation and fibrinolysis.
- TAFI activation by thrombin suppresses fibrinolysis by inhibiting tPA cofactor activity.
- TAFIa plays a significant role in downregulating fibrinolysis, even in the presence of fibrin degradation products.
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