Platelets are essential to the pathogenesis of atherothrombosis and the formation of a hemostatic plug. The preclinical animal models, mice in particular, provide a major platform to evaluate the safety and efficacy of antiplatelet drugs. However, these studies are limited by inherent differences between human and mouse platelets and many drugs’ species-selectivity.
The hemostatic plug stability and formation were quantified and visualized by intravital spinning disk confocal microscopy following laser ablation injury to the saphenous vein to demonstrate the power of this new model. The pretreatment of mice with standard dual antiplatelet therapy (Aspirin+Ticagrelor) or PAR1 inhibitor, L-003959712 (an analog of vorapaxar), significantly reduced platelet adhesion to the site of injury and mildly prolonged the bleeding time. This novel mouse model is proposed to provide a robust platform to predict and test the efficacy and safety of experimental antiplatelet drugs and characterize the hemostatic function of patient, stored, and synthetic platelets.
In conclusion, a novel method for the adoptive transfer of human platelets into thrombocytopenic mice allows for the direct study of human platelets in an in vivo environment. The studies on the antihemostatic effect of PAR1 inhibition in the presence and absence of DAPT validate the platelet mouse model as a robust platform to predict and test experimental antiplatelet drugs’ efficacy and safety.