INHIBIDOR DE LA FIBRINOLISIS ACTIVADO POR TROMBINA (TAFI): NEXO ENTRE LA COAGULACION Y LA FIBRINOLISIS





INHIBIDOR DE LA FIBRINOLISIS ACTIVADO POR TROMBINA (TAFI): NEXO ENTRE LA COAGULACION Y LA FIBRINOLISIS

(especial para SIIC © Derechos reservados)
El inhibidor de la fibrinólisis activado por trombina es una enzima que vincula los procesos de coagulación y fibrinólisis, y que podría desempeñar funciones importantes en patologías de origen inflamatorio.
antovic9.jpg Autor:
Jovan P Antovic
Columnista Experto de SIIC

Institución:
Novo Nordisk ROSEE


Artículos publicados por Jovan P Antovic
Recepción del artículo
31 de Agosto, 2005
Aprobación
6 de Septiembre, 2005
Primera edición
10 de Abril, 2006
Segunda edición, ampliada y corregida
7 de Junio, 2021

Resumen
El inhibidor de la fibrinólisis activado por trombina (TAFI) es otro vínculo, descrito recientemente, entre la coagulación y la fibrinólisis. Su proenzima pro-TAFI (procarboxipeptidasa U, procarboxipeptidasa B plasmática) es una glucoproteína sintetizada en el hígado como un prepropéptido compuesto por 423 aminoácidos con un peso molecular de 55 kD. La pro-TAFI es activada por tripsina, plasmina y, más eficientemente, por el complejo trombina/trombomodulina, lo que genera la forma activa de la enzima TAFI (carboxipeptidasa U, B). El TAFI es altamente inestable, con una vida media de solamente 10 minutos a 37ºC debido a la inestabilidad proteolítica y a su degradación dependiente de la temperatura. El TAFI disminuye la fibrinólisis mediante el clivaje de arginina y lisina del extremo carboxiterminal de la fibrina y limita tanto la unión con el plasminógeno como la formación de plasmina. El TAFI es dependiente de la generación de trombina y, en consecuencia, los trastornos que involucran un aumento o una disminución de ésta (como la resistencia a la proteína C-reactiva, en el primero de los casos, y la hemofilia, en el segundo) pueden inducir cambios en los niveles de formas diferentes del TAFI y, mediante la influencia sobre la fibrinólisis, alterar la estabilidad de los coágulos. Además, se describió el papel del TAFI como potencial factor de riesgo de enfermedad cardiovascular. Para finalizar, se vio que el TAFI cambia en patologías asociadas con inflamación, en los trastornos lipídicos asociados con la aterosclerosis y en la curación o cicatrización de las heridas. Sin embargo, su papel definitivo sobre distintos trastornos debe aún ser probado. Es por ello que en el futuro cercano los objetivos de la investigación de esta molécula proteica deberían ser tanto la determinación de su papel como los esfuerzos necesarios para el desarrollo de métodos precisos y confiables para la determinación ex vivo de la forma activa de la enzima (TAFI).

Palabras clave
Inhibidor de la fibrinólisis activado por trombina (TAFI), carboxipeptidasa U, carboxipeptidasa plasmática B, coagulación, fibrinólisis


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Abstract
Thrombin activatable fibrinolysis inhibitor (TAFI) is another, recently described, link between coagulation and fibrinolysis. Its proenzyme pro-TAFI (procarboxypeptidase U, plasma procarboxypeptidase B) is a glycoprotein synthesized in the liver as a prepropeptide consisting of 423 amino acids with a molecular weight of 55 kD. Pro-TAFI is activated by trypsin, plasmin and thrombin, by most effectively by thrombin/thrombomodulin complex forming active form of enzyme – TAFI (carboxypeptidase U, B). TAFI is highly unstable, with a half-life of only 10 minutes at 37C due to proteolytic instability and temperature dependent degradation. TAFI down-regulates fibrinolysis by cleaveing off carboxy terminal arginine and lysine from fibrin and limits plasminogen binding as well as plasmin formation. TAFI is dependent on thrombin generation and therefore clinical conditions involving increased (APC resistance) or decreased thrombin generation (haemophilia) could induce changes in the levels of different forms of TAFI and by influencing fibrinolysis alter clot stability. Furthermore, the role of TAFI as potential risk factor for cardiovascular disease has been described. Finally, TAFI changes in conditions associated with inflammation, lipid disturbances in atherosclerosis and wound healing have been observed. However, the definitive role of TAFI in many clinical conditions has yet to be proven. That, together with efforts to develop accurate and precise methods for the ex vivo determination of TAFI (the active form of the enzyme) should be the main goals of TAFI investigation in the near future.

Key words
Thrombin activatable fibrinolysis inhibitor (TAFI), carboxypeptidase U, plasma carboxypeptidase B, coagulation, fibrinolysis


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Clasificación en siicsalud
Artículos originales > Expertos del Mundo >
página   www.siicsalud.com/des/expertocompleto.php/

Especialidades
Principal: Bioquímica
Relacionadas: Diagnóstico por Laboratorio, Hematología, Medicina Interna



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Patrocinio y reconocimiento:
El apoyo financiero para esta investigation fue proporcionado por Coagulation Research Foundation, Karolinska Institute (Professor Margareta Blombäck); the Heart and Lung Foundation Sweden; Swedish Society for Medical Research; Baxter Sweden; American Diagnostica Inc.; Novo Nordisk, y the Eric K. Fernström Foundation.
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