TAFI (thrombin-activatable fibrinolysis inhibitor)
|Synonym||Plasma Procarboxy Peptidase B, Plasma Procarboxy Peptidase U|
|IUB denotation||EC 220.127.116.11|
|Molecular mass||60.000 Da|
|Plasma concentration||approx. 2.5 µg/ml|
TAFI is synthesized in the liver and circulates in plasma as a proenzyme, to a certain extent in complex with plasminogen. Its main path of activation to TAFIa is mediated by the thrombin/thrombomodulin-complex, but activation by thrombin alone or plasmin is also possible. TAFIa inhibits fibrinolysis by cleaving off C-terminal lysin residues from fibrin. This prevents t-PA and plasminogen to bind to fibrin, subsequently leading to a delayed clot lysis.
An increased level of TAFI leads to a state of hyperfibrinolysis, causing such patients to have an elevated risk of thrombosis. Additionally, another patophysiologic function of TAFI is also debated: Activated TAFI inhibits a premature lysis of a thrombus. Patients with factor VIII or factor IX deficiency (haemophilia A or B) suffer from a premature lysis of the fibrin clot due to the low prothrombin activation, which in turn, leads to a deficiency of activated TAFI. Discussions are ongoing whether the bleeding complications in patients with haemophilia A or B could be a result of a defect in stabilisation rather than the missing formation of a thrombus.
- Differential diagnosis in haemorrhagic diathesis
- Idiopathic thromboembolism
- Bajzar L, Manuel R, Nesheim ME. Purification and Characterization of TAFI, a Thrombin-activatable Fibrinolysis Inhibitor. J Biol Chem 270, 14477-14484, 1995.
- Silveira A et al. Plasma Procarboxypeptidase U in Men with Symptomatic Coronary Artery Disease. Thromb Haemost 84, 364-368, 2000.
- Mosiner LO et al. Plasma TAFI Levels Influence the Clot Lysis Time in Healthy Individuals in the Presence of an Intact Intrinsic Pathway of Coagulation. Thromb Haemost 80, 829-835, 1998.
- Nesheim M et al. Thrombin, Thrombomodulin and TAFI in the Molecular Link between Coagulation and Fibrinolysis. Thromb Haemost 78 (1), 386-391, 1997.
- Chetaille P et al. Plasma TAFI Antigen Variations in Healthy Subjects. Thromb Haemost 83, 902-905, 2000.
- van Tilburg N et al. Thrombin activatable fibrinolysis inhibitor and the risk for deep vein thrombosis. Blood 95, 2855-2859, 2000.
- Grosso G, Vikerfors A, Woodhams B, Adam M, Bremme K, Holmström M, Ågren A, Eelde A, Bruzelius M, Svenungsson E, Antovic A. Thrombin activatable fibrinolysis inhibitor (TAFI) - A possible link between coagulation and complement activation in the antiphospholipid syndrome (APS). Thromb Res. Oct;158:168-173 2017.
- Dempfle CE. The TAFI system. The new role of fibrinolysis. Hamostaseologie. Sep;27(4):278-81, 2007.
- Antovic JP, Blombäck M. Thrombin-activatable fibrinolysis inhibitor antigen and TAFI activity in patients with APC resistance caused by factor V Leiden mutation. Thromb Res. Apr 1;106(1):59-62, 2002.