Factor Xa activation of factor V is of paramount importance in initiating the coagulation system: lessons from a tick salivary protein.
Research article published in Circulation (2013)
Abstract
BACKGROUND: Generation of active procoagulant cofactor factor Va (FVa) and its subsequent association with the enzyme activated factor X (FXa) to form the prothrombinase complex is a pivotal initial event in blood coagulation and has been the subject of investigative effort, speculation, and controversy. The current paradigm assumes that FV activation is initiated by limited proteolysis by traces of (meizo) thrombin. METHODS AND RESULTS: Recombinant tick salivary protein TIX-5 was produced and anticoagulant properties were studied with the use of plasma, whole blood, and purified systems. Here, we report that TIX-5 specifically inhibits FXa-mediated FV activation involving the B domain of FV and show that FXa activation of FV is pivotal for plasma and blood clotting. Accordingly, tick feeding is impaired on TIX-5 immune rabbits, displaying the in vivo importance of TIX-5. CONCLUSIONS: Our data elucidate a unique molecular mechanism by which ticks inhibit the host's coagulation system. From our data, we propose a revised blood coagulation scheme in which direct FXa-mediated FV activation occurs in the initiation phase during which thrombin-mediated FV activation is restrained by fibrinogen and inhibitors.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Generation of active procoagulant cofactor factor Va (FVa) and its subsequent association with the enzyme activated factor X (FXa) to form the prothrombinase complex is a pivotal initial event in blood coagulation and has been the subject of investigative effort, speculation, and controversy. The...
Por qué esto importa para la hirudoterapia
Este estudio investigó la proteína recombinante de la saliva de garrapata TIX-5, demostrando que inhibe específicamente la activación del factor V mediada por el factor Xa—un evento iniciador pivotal en la coagulación sanguínea—y que esta inhibición altera la alimentación de la garrapata en conejos inmunizados in vivo. Los autores proponen un modelo revisado de coagulación en el cual la activación directa del FV mediada por FXa ocurre durante la iniciación, mientras que la activación del FV mediada por trombina está restringida. Para el dominio de ASH, si bien este estudio concierne a un anticoagulante salival de un artrópodo hematófago—un campo afín a la investigación del secretoma de la sanguijuela—el organismo es una garrapata, no una sanguijuela, y el mecanismo de TIX-5 (bloqueo de la activación del FV mediada por FXa) es distinto del de anticoagulantes conocidos de la sanguijuela, como la hirudina. Por lo tanto, la relevancia se limita a la biología comparativa de anticoagulantes de artrópodos hematófagos, más que a una aplicación directa a la hirudoterapia.
Citación
Factor Xa activation of factor V is of paramount importance in initiating the coagulation system: lessons from a tick salivary protein.
Schuijt et al. · Circulation, 2013
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Añadido a la biblioteca ASH: May 28, 2026 · Última actualización del sitio: 18 de junio de 2026