Thrombin Activatable Fibrinolysis Inhibitor (TAFI): A Molecular Link Between Coagulation and Fibrinolysis
2010
Autori
Miljić, PredragHeylen, Evelien
Willemse, Johan
Đorđević, Valentina
Radojković, Dragica
Colović, Milica
Elezović, Ivo
Hendriks, Dirk
Konferencijski prilog (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Although the maintenance of precise balance between coagulation and fibrinolysis is of utmost importance for normal haemostasis, until recently these two systems were considered as completely separate mechanisms involved in the process of formation and dissolution of blood clot. Thrombin activatable fibrinolysis inhibitor (TAFI) is a recently described attenuator of the fibrinolytic rate and is considered to be the molecular link between coagulation and fibrinolysis. TAFI circulates in plasma as an inactive precursor and its conversion in active enzyme (TAFIa) occurs by the action of thrombin or plasmin, but most efficiently by thrombin in the presence of its cofactor thrombomodulin. Once generated, TAFI down-regulates fibrinolysis by removing C-terminal lysine residues from partially degraded fibrin; thereby preventing the upregulation of plasminogen binding and activation. Because TAFI is activated by thrombin on one side, and acts as the attenuator of fibrinolysis on another side, i...t enables fine synchronization between these two systems. The antifibrinolytic function of TAFI mostly depends on TAFI concentration, the rate of its activation and the half-life of TAFIa in plasma. Changes in thrombin generation can have a profound effect on the rate of TAFI activation, and consequently on the rate of fibrinolysis. Therefore, it has been hypothesized that increased thrombin generation seen in thrombophilia patients may enhance TAFI activation, leading to a hypofibrinolytic state, which may further contribute to the thrombotic tendency. However, the results of several studies, in which relation between TAFI level and the occurrence of thromboembolic complications in carriers of hereditary thrombophilia have been investigated, were not consistent.
Ključne reči:
TAFI / hereditary thrombophilia / fibrinolysisIzvor:
Srpski arhiv za celokupno lekarstvo, 2010, 138, 74-78Izdavač:
- Srpsko lekarsko društvo, Beograd
Finansiranje / projekti:
- Molekularno genetski markeri klonskog preobražaja matičnih ćelija hematopoeze (RS-MESTD-MPN2006-2010-145061)
DOI: 10.2298/SARH10S1074M
ISSN: 0370-8179
PubMed: 20229688
WoS: 000277366200014
Scopus: 2-s2.0-77951243964
Institucija/grupa
Institut za molekularnu genetiku i genetičko inženjerstvoTY - CONF AU - Miljić, Predrag AU - Heylen, Evelien AU - Willemse, Johan AU - Đorđević, Valentina AU - Radojković, Dragica AU - Colović, Milica AU - Elezović, Ivo AU - Hendriks, Dirk PY - 2010 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/426 AB - Although the maintenance of precise balance between coagulation and fibrinolysis is of utmost importance for normal haemostasis, until recently these two systems were considered as completely separate mechanisms involved in the process of formation and dissolution of blood clot. Thrombin activatable fibrinolysis inhibitor (TAFI) is a recently described attenuator of the fibrinolytic rate and is considered to be the molecular link between coagulation and fibrinolysis. TAFI circulates in plasma as an inactive precursor and its conversion in active enzyme (TAFIa) occurs by the action of thrombin or plasmin, but most efficiently by thrombin in the presence of its cofactor thrombomodulin. Once generated, TAFI down-regulates fibrinolysis by removing C-terminal lysine residues from partially degraded fibrin; thereby preventing the upregulation of plasminogen binding and activation. Because TAFI is activated by thrombin on one side, and acts as the attenuator of fibrinolysis on another side, it enables fine synchronization between these two systems. The antifibrinolytic function of TAFI mostly depends on TAFI concentration, the rate of its activation and the half-life of TAFIa in plasma. Changes in thrombin generation can have a profound effect on the rate of TAFI activation, and consequently on the rate of fibrinolysis. Therefore, it has been hypothesized that increased thrombin generation seen in thrombophilia patients may enhance TAFI activation, leading to a hypofibrinolytic state, which may further contribute to the thrombotic tendency. However, the results of several studies, in which relation between TAFI level and the occurrence of thromboembolic complications in carriers of hereditary thrombophilia have been investigated, were not consistent. PB - Srpsko lekarsko društvo, Beograd C3 - Srpski arhiv za celokupno lekarstvo T1 - Thrombin Activatable Fibrinolysis Inhibitor (TAFI): A Molecular Link Between Coagulation and Fibrinolysis EP - 78 SP - 74 VL - 138 DO - 10.2298/SARH10S1074M ER -
@conference{ author = "Miljić, Predrag and Heylen, Evelien and Willemse, Johan and Đorđević, Valentina and Radojković, Dragica and Colović, Milica and Elezović, Ivo and Hendriks, Dirk", year = "2010", abstract = "Although the maintenance of precise balance between coagulation and fibrinolysis is of utmost importance for normal haemostasis, until recently these two systems were considered as completely separate mechanisms involved in the process of formation and dissolution of blood clot. Thrombin activatable fibrinolysis inhibitor (TAFI) is a recently described attenuator of the fibrinolytic rate and is considered to be the molecular link between coagulation and fibrinolysis. TAFI circulates in plasma as an inactive precursor and its conversion in active enzyme (TAFIa) occurs by the action of thrombin or plasmin, but most efficiently by thrombin in the presence of its cofactor thrombomodulin. Once generated, TAFI down-regulates fibrinolysis by removing C-terminal lysine residues from partially degraded fibrin; thereby preventing the upregulation of plasminogen binding and activation. Because TAFI is activated by thrombin on one side, and acts as the attenuator of fibrinolysis on another side, it enables fine synchronization between these two systems. The antifibrinolytic function of TAFI mostly depends on TAFI concentration, the rate of its activation and the half-life of TAFIa in plasma. Changes in thrombin generation can have a profound effect on the rate of TAFI activation, and consequently on the rate of fibrinolysis. Therefore, it has been hypothesized that increased thrombin generation seen in thrombophilia patients may enhance TAFI activation, leading to a hypofibrinolytic state, which may further contribute to the thrombotic tendency. However, the results of several studies, in which relation between TAFI level and the occurrence of thromboembolic complications in carriers of hereditary thrombophilia have been investigated, were not consistent.", publisher = "Srpsko lekarsko društvo, Beograd", journal = "Srpski arhiv za celokupno lekarstvo", title = "Thrombin Activatable Fibrinolysis Inhibitor (TAFI): A Molecular Link Between Coagulation and Fibrinolysis", pages = "78-74", volume = "138", doi = "10.2298/SARH10S1074M" }
Miljić, P., Heylen, E., Willemse, J., Đorđević, V., Radojković, D., Colović, M., Elezović, I.,& Hendriks, D.. (2010). Thrombin Activatable Fibrinolysis Inhibitor (TAFI): A Molecular Link Between Coagulation and Fibrinolysis. in Srpski arhiv za celokupno lekarstvo Srpsko lekarsko društvo, Beograd., 138, 74-78. https://doi.org/10.2298/SARH10S1074M
Miljić P, Heylen E, Willemse J, Đorđević V, Radojković D, Colović M, Elezović I, Hendriks D. Thrombin Activatable Fibrinolysis Inhibitor (TAFI): A Molecular Link Between Coagulation and Fibrinolysis. in Srpski arhiv za celokupno lekarstvo. 2010;138:74-78. doi:10.2298/SARH10S1074M .
Miljić, Predrag, Heylen, Evelien, Willemse, Johan, Đorđević, Valentina, Radojković, Dragica, Colović, Milica, Elezović, Ivo, Hendriks, Dirk, "Thrombin Activatable Fibrinolysis Inhibitor (TAFI): A Molecular Link Between Coagulation and Fibrinolysis" in Srpski arhiv za celokupno lekarstvo, 138 (2010):74-78, https://doi.org/10.2298/SARH10S1074M . .