Comparison of antithrombotic and hemorrhagic effects of edoxaban, a novel factor Xa inhibitor, with unfractionated heparin, dalteparin, lepirudin and warfarin in rats
Comparative study published in Thrombosis research (2013)
Abstract
BACKGROUND: Edoxaban is a novel, potent and orally active direct Factor Xa (FXa) inhibitor under development for prophylaxis and treatment of thromboembolic diseases. Properties of dose response and margin of safety of anticoagulants are the key factors for a positive risk/benefit of novel oral anticoagulants. OBJECTIVES: To compare the dose response of antithrombotic effect and margin of safety between antithrombotic and hemorrhagic effects of edoxaban with conventional anticoagulants, unfractionated heparin (UFH), dalteparin (low molecular weight heparin), lepirudin, and warfarin in rat models of thrombosis and hemorrhage. METHODS: Rats were treated with edoxaban, UFH, dalteparin, and lepirudin by continuous intravenous (iv) infusion, or with oral warfarin for 4 days before inducing thrombosis or bleeding. Thrombosis was induced by inserting a platinum wire into the inferior vena cava for 60 minutes. Tail template bleeding time was measured after making an incision on the tail. RESULTS: In rats, iv infusion of edoxaban inhibited venous thrombosis in a dose-dependent manner. The other anticoagulants also exerted dose-dependent antithrombotic effects. The slopes of the dose-response curves of edoxaban were significantly shallower than the slopes of UFH, dalteparin, and warfarin. At supratherapeutic doses, edoxaban prolonged bleeding time in a rat tail bleeding model. To determine bleeding risk, the margins between antithrombotic and bleeding-time prolongation were compared. The margins of safety of edoxaban were wider than those of UFH, dalteparin, lepirudin, and warfarin. CONCLUSIONS: These results suggest that edoxaban may be more easily controlled and has the potential for a more positive risk/benefit ratio compared to conventional anticoagulants.
Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.
Resumen
Edoxaban is a novel, potent and orally active direct Factor Xa (FXa) inhibitor under development for prophylaxis and treatment of thromboembolic diseases.
Por qué esto importa para la hirudoterapia
Este estudio comparó los efectos antitrombóticos y hemorrágicos del edoxabán, un nuevo inhibidor oral del factor Xa, con los de la heparina no fraccionada, la dalteparina, la lepirudina y la warfarina en modelos de trombosis y hemorragia en ratas. La lepirudina se utilizó como uno de varios anticoagulantes de referencia administrados mediante infusión intravenosa continua. El estudio halló que el edoxabán presentó márgenes de seguridad más amplios entre el efecto antitrombótico y la prolongación del tiempo de sangrado que todos los comparadores, incluida la lepirudina. Para el ámbito de ASH, la conexión es indirecta: la lepirudina aparece únicamente como agente comparador, y el foco del estudio es el agente nuevo edoxabán, más que la hirudoterapia. La advertencia clave es que se trata de datos de modelos animales, y el resumen no describe el origen bioquímico ni el mecanismo de la lepirudina.
Citación
Comparison of antithrombotic and hemorrhagic effects of edoxaban, a novel factor Xa inhibitor, with unfractionated heparin, dalteparin, lepirudin and warfarin in rats
Morishima Y et al. · Thrombosis research, 2013
Contexto clínico relacionado
Explore cómo esta investigación se conecta con la práctica clínica
Añadido a la biblioteca ASH: May 27, 2026 · Última actualización del sitio: 18 de junio de 2026