Yamazaki M, Asakura H, Aoshima K, Saito M, Jokaji H, Uotani C, Kumabashiri I, Morishita E, Ikeda T, Matsuda T
Department of Internal Medicine (III), Kanazawa University School of Medicine, Japan.
Semin Thromb Hemost. 1996;22(3):255-9. doi: 10.1055/s-2007-999016.
We investigated the protective effects of DX-9065a, an orally active, newly synthesized, and specific inhibitor of factor Xa, against experimental disseminated intravascular coagulation (DIC) in rats. Experimental DIC was induced by a 4 hour sustained infusion of thromboplastin at a dose of 2.5 mg/kg. The rats were orally administered DX-9065a at 10, 30, 100 mg/kg 30 minutes before thromboplastin injection. In this DIC model, DX-9065a showed a protective effect against DIC, at all doses and in all parameters, including fibrin(ogen) degradation products, fibrinogen level, thrombin-antithrombin III complex level, prothrombin time (PT), activated partial thromboplastin time (APTT), platelet count, and the number of renal glomeruli with fibrin thrombi. When DX-9065a was orally administered at 100 mg/kg without thromboplastin, no significant changes were seen in hemostatic parameters except PT and APTT, and no fibrin thrombi or abnormal bleeding were seen in renal specimens. These findings suggested that the new oral anti-Xa drug, DX-9065a, has a protective effect against thromboplastin-induced DIC model with little risk of bleeding.
我们研究了新型口服活性Xa因子特异性抑制剂DX-9065a对大鼠实验性弥散性血管内凝血（DIC）的保护作用。通过以2.5mg/kg的剂量持续输注凝血活酶4小时诱导实验性DIC。在注射凝血活酶前30分钟，给大鼠口服10、30、100mg/kg的DX-9065a。在该DIC模型中，DX-9065a在所有剂量下对DIC的所有参数均显示出保护作用，这些参数包括纤维蛋白（原）降解产物、纤维蛋白原水平、凝血酶-抗凝血酶III复合物水平、凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）、血小板计数以及有纤维蛋白血栓的肾小球数量。当在未注射凝血活酶的情况下给大鼠口服100mg/kg的DX-9065a时，除PT和APTT外，止血参数未见明显变化，肾脏标本中也未见纤维蛋白血栓或异常出血。这些结果表明，新型口服抗Xa药物DX-9065a对凝血活酶诱导的DIC模型具有保护作用，且出血风险较小。
