Key result
In a rabbit model of arteriovenous shunt thrombosis stimulated with tissue factor, TAK-442 dose-dependently reduced thrombus formation by approximately 40% at 37.5 µg/kg and 60% at 75 µg/kg (P ≤ 0.025).
Why the study?
Does TAK-442 reduce thrombus formation in a rabbit model of arteriovenous shunt thrombosis stimulated with tissue factor?
Does TAK-442 reduce thrombus formation in a rabbit model of arteriovenous shunt thrombosis stimulated with tissue factor?
TAK-442 effectively reduces thrombus formation in a tissue factor-stimulated arteriovenous shunt model in rabbits, suggesting efficacy in conditions where thrombosis is driven by the tissue factor pathway.
TAK-442 reduced thrombus in this tissue factor-stimulated rabbit model; leaves open translation to human arterial thrombosis.
OBJECTIVE: Arterial thrombosis is triggered by tissue factor, which is a transmembrane glycoprotein can be released into the blood circulation after plaque rupture. Animal models with reflecting ruptured plaque lesions will be useful to understand efficacy of anticoagulant. In this study, we sought to improve a common arteriovenous shunt model in rabbits, aiming for a model of thrombosis stimulated with tissue factor, and to investigate the anti-thrombotic effect of a direct factor Xa inhibitor TAK-442 in the model. RESULTS: In the model where thrombus was stimulated with a thrombogenic silk thread soaked with recombinant human tissue factor, thrombus formation was significantly reduced by TAK-442 at more than 37.5 µg/kg, accompanied with prolonged plasma hemostatic parameters. Although efficacious doses of anti-coagulants in ordinary arteriovenous thrombosis models are widely reported to be higher than those in venous thrombosis models, TAK-442 showed its efficacy in the present arteriovenous shunt thrombosis model, with equivalent sensitivity in a previously reported venous model. TAK-442 might be effective under conditions thrombus formed is more influenced by tissue factor pathway.
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Shinozawa et al. (2018) studied Arteriovenous shunt thrombosis (animal model) (n=14). TAK-442 vs. Vehicle control was evaluated on Thrombus formation (thrombus weight) (60% reduction at 75 µg/kg, p=≤0.025). In a rabbit model of arteriovenous shunt thrombosis stimulated with tissue factor, TAK-442 dose-dependently reduced thrombus formation by approximately 40% at 37.5 µg/kg and 60% at 75 µg/kg (P ≤ 0.025).
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