Tianjin Medical University School, Tianjin, 300070, People's Republic of China.
Department of Pharmacology, Dalian Medical University, Dalian, 116044, Liaoning, People's Republic of China.
J Thromb Thrombolysis. 2019 Jan;47(1):80-86. doi: 10.1007/s11239-018-1743-x.
In recent years, oral factor Xa inhibitors have become a research focus as anticoagulant drugs. Zifaxaban is the first oral FXa inhibitor to enter clinical trials in China. The aim of this study was to determine the inhibitory effect of zifaxaban on thrombosisthrough a model ofinferior vena cava (IVC) thrombosis in rabbits. IVC thrombosis model was established by electrical injury and stenosis, and zifaxaban was administered (p.o.) for 5 consecutive days, then coagulation indicators and bleeding were observed. The results showed that zifaxaban had obvious inhibitory effects on FXa, and had a significant inhibitory effect on IVC thrombosis induced by electrical damage and stenosis. The effect of zifaxaban was similar to that of rivaroxaban, but the bleeding side-effects of zifaxaban were less severe than those of rivaroxaban. Zifaxaban could prolong the prothrombin time and activated partial thromboplastin time of plasma similar to that of other oral FXa inhibitors. Zifaxaban had a significant inhibitory effect on FXa, but it had no obvious effect on other coagulation factors, major anticoagulant factors or fibrinolytic indices. Our results suggest that zifaxaban had specific inhibitory effects on FXa and inhibited IVC thrombosis in rabbits with its hemorrhagic effect was less than that of rivaroxaban. Zifaxaban is ecpected to be developed as a new drug for the prevention of deep venous thrombosis, providing more medication options for patients with such disease, more research is required to support it in the future.
近年来,口服因子 Xa 抑制剂已成为抗凝药物的研究热点。利伐沙班是第一个进入中国临床试验的口服 FXa 抑制剂。本研究旨在通过兔下腔静脉(IVC)血栓形成模型确定利伐沙班对血栓形成的抑制作用。通过电损伤和狭窄建立 IVC 血栓形成模型,并连续 5 天给予利伐沙班(p.o.),然后观察凝血指标和出血情况。结果表明,利伐沙班对 FXa 有明显的抑制作用,对电损伤和狭窄引起的 IVC 血栓形成有显著抑制作用。利伐沙班的作用与 rivaroxaban 相似,但利伐沙班的出血副作用比 rivaroxaban 轻。利伐沙班可延长血浆凝血酶原时间和活化部分凝血活酶时间,与其他口服 FXa 抑制剂相似。利伐沙班对 FXa 有明显的抑制作用,但对其他凝血因子、主要抗凝因子或纤维蛋白溶解指标无明显影响。我们的研究结果表明,利伐沙班对 FXa 有特异性抑制作用,可抑制兔 IVC 血栓形成,且出血作用小于 rivaroxaban。利伐沙班有望开发成为预防深静脉血栓形成的新药,为该疾病患者提供更多的治疗选择,但仍需要更多的研究来支持它。