Asmael Al-Azzawi Huda Moutaz, Paolini Rita, McCullough Michael, Reilly Lorraine O', Hamza Syed Ameer, Hadjigol Sara, Yap Tami, Celentano Antonio
Melbourne Dental School, The University of Melbourne Melbourne Dental School, Victoria, Australia.
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria, 3052, Australia.
J Thromb Thrombolysis. 2025 Mar;58(3):427-432. doi: 10.1007/s11239-024-03066-y. Epub 2024 Dec 19.
Animal models of thrombosis play a critical role in research, helping us understand the mechanisms of hemostasis and thrombus formation, as well as in the screening of anti-thrombotic drugs. This study aimed to evaluate the safety profile of two anticoagulants in murine research and to assess coagulation parameters, including prothrombin time (PT) and activated partial thromboplastin time (aPTT), using the VETSCAN VSpro coagulation analyzer in wild-type (C57BL/6) mice following administration of anticoagulants. Two experiments were conducted involving a total of sixty wild-type mice that received two common anticoagulants. Warfarin was administered in the drinking water at varying dosages, while dabigatran was incorporated into a custom-chow diet at two dosages (10 mg/g and 15 mg/g chow). The VSpro was used to establish a reference range for PT and aPTT values in untreated wild-type mice and to monitor coagulation changes in mice undergoing anticoagulant therapy. Dabigatran was well tolerated at both concentrations (10 mg/g and 15 mg/g chow), while warfarin was safe at a concentration of 2.5 mg/L, resulting in a doubling of PT and aPTT compared to baseline levels. Although the VSpro effectively detected coagulation abnormalities in murine models, certain limitations were observed, including out-of-range measurements in cases of coagulopathy. This study provides insights into safe anticoagulant dosages for murine models, supporting the use of dabigatran at 10 mg/g and 15 mg/g chow and warfarin at 2.5 mg/L. The VSpro analyzer was able to monitor coagulation parameters under these conditions, making it a feasible tool for murine research.
血栓形成的动物模型在研究中起着关键作用,有助于我们理解止血和血栓形成的机制,以及在抗血栓药物的筛选中发挥作用。本研究旨在评估两种抗凝剂在小鼠研究中的安全性,并使用VETSCAN VSpro凝血分析仪,在野生型(C57BL/6)小鼠中给予抗凝剂后,评估包括凝血酶原时间(PT)和活化部分凝血活酶时间(aPTT)在内的凝血参数。进行了两项实验,总共60只野生型小鼠接受了两种常用的抗凝剂。华法林以不同剂量添加到饮用水中,而达比加群以两种剂量(10mg/g和15mg/g食物)添加到定制饲料中。VSpro用于建立未处理的野生型小鼠PT和aPTT值的参考范围,并监测接受抗凝治疗小鼠的凝血变化。达比加群在两种浓度(10mg/g和15mg/g食物)下耐受性良好,而华法林在2.5mg/L的浓度下是安全的,与基线水平相比,PT和aPTT增加了一倍。尽管VSpro有效地检测了小鼠模型中的凝血异常,但也观察到了某些局限性,包括在凝血病病例中出现超出范围的测量值。本研究为小鼠模型的安全抗凝剂剂量提供了见解,支持在10mg/g和15mg/g食物剂量下使用达比加群,以及在2.5mg/L剂量下使用华法林。VSpro分析仪能够在这些条件下监测凝血参数,使其成为小鼠研究中的一种可行工具。