Department of Microbiology, Immunology and Pathology, Clinical Pathology Section, Colorado State University, Fort Collins, CO, USA.
Seattle Veterinary Specialists, Kirkland, WA, USA.
Basic Clin Pharmacol Toxicol. 2018 Sep;123(3):257-262. doi: 10.1111/bcpt.13015. Epub 2018 May 6.
The dog is an important companion animal and also purpose-bred for research studies. Coagulopathies in dogs are common, although the availability of blood products for therapy is inconsistent throughout the profession. A pro-coagulant therapeutic that is readily available and easily stored would be useful for the treatment of coagulopathies. Tricarbonyldichlororuthenium (II) dimer [Carbon monoxide-releasing molecule-2 (CORM-2)] acts as a prothrombotic agent in plasma by increasing the velocity of clot formation and clot strength, and by decreasing the clot's vulnerability to fibrinolysis. We sought to test CORM-2's effect on coagulation and fibrinolysis in vitro in canine plasma using thromboelastography. Measures of the rate of clot formation and clot strength in plasma without CORM-2 were highly correlated with fibrinogen concentration. We found that CORM-2 significantly enhanced the rate of clot formation and clot strength and significantly reduced the rate of fibrinolysis and the clot lysis time. The per cent change in rate of clot formation and clot strength was not significantly correlated with fibrinogen concentration, indicating that CORM-2's pro-coagulant effect is not dependent on fibrinogen concentration. This study corroborates studies in other species that show that CORM-2 is pro-coagulant in plasma, and lays the groundwork for developing CORM-2 as a therapeutic agent for canine coagulopathies. Future studies will evaluate the effect of CORM-2 on whole blood both in vitro and in vivo.
狗是一种重要的伴侣动物，也被专门用于研究目的。犬类的凝血异常很常见，尽管整个行业中治疗用的血液制品供应并不一致。一种易于获得且易于储存的促凝治疗剂对于治疗凝血异常将非常有用。三羰基二氯合钌（II）二聚体[一氧化碳释放分子-2（CORM-2）]通过增加血栓形成速度和血栓强度，以及降低血栓对纤维蛋白溶解的易感性，在血浆中充当促血栓形成剂。我们试图使用血栓弹性描记术在犬血浆中体外测试 CORM-2 对凝血和纤维蛋白溶解的影响。没有 CORM-2 时的血浆中血栓形成速度和血栓强度的测量值与纤维蛋白原浓度高度相关。我们发现 CORM-2 显著增强了血栓形成速度和血栓强度，显著降低了纤维蛋白溶解速度和血栓溶解时间。血栓形成速度和血栓强度的百分比变化与纤维蛋白原浓度没有显著相关性，表明 CORM-2 的促凝作用不依赖于纤维蛋白原浓度。这项研究证实了其他物种中的研究结果，即 CORM-2 在血浆中具有促凝作用，并为开发 CORM-2 作为犬类凝血异常的治疗剂奠定了基础。未来的研究将评估 CORM-2 在体外和体内对全血的影响。
