Fujishima Y, Yokota K, Sukamoto T
Department of Pharmacology, Pharmaceutical Research Laboratories, Kanebo, Ltd., Osaka, Japan.
Thromb Res. 1998 Sep 1;91(5):221-7. doi: 10.1016/s0049-3848(98)00094-2.
Danaparoid sodium (danaparoid) is a low molecular weight heparinoid with anticoagulation properties, which mainly consists of heparan sulfate. Compared with heparin sodium (heparin), danaparoid has a much higher anti-Xa/anti-thrombin ratio. We compared the effect of danaparoid on endotoxin-induced experimental disseminated intravascular coagulation (DIC) in rats with heparin. A bolus injection of endotoxin (10 mg/kg) induced gradual decreases in the platelet count, and the plasma fibrinogen, antithrombin III (AT-III) and heparin cofactor II levels, as well as an increase in the fibrinogen/fibrin degradation products level from 1 to 6 hours after the injection, indicating that both coagulation and fibrinolysis were activated. The intravenous administration of danaparoid or heparin 3 hours after the endotoxin injection inhibited the endotoxin-induced decreases in the platelet count and plasma fibrinogen level and also inhibited the endotoxin-induced increase in glomerular fibrin deposition in the kidney. Differences between danaparoid and heparin were observed in their effects on the plasma AT-III level and clotting time. Danaparoid significantly inhibited both the decrease in the plasma AT-III level and the prolongation of the prothrombin time induced by endotoxin, where as heparin showed no effect on those responses. Moreover, danaparoid enhanced the prolongation of the activated partial thromboplast in time induced by endotoxin to a lesser degree than heparin. These findings suggest that the effects of danaparoid on the endotoxin-induced decrease of the plasma AT-III level and the prolongation of the clotting time are more advantageous than those of heparin. The results may have been due to a higher anti-Xa/anti-thrombin ratio of danaparoid than that of heparin, indicating that danaparoid may be useful in the treatment of DIC.
达那肝素钠（达那肝素）是一种具有抗凝特性的低分子量类肝素，主要由硫酸乙酰肝素组成。与肝素钠（肝素）相比，达那肝素具有更高的抗Xa/抗凝血酶比率。我们比较了达那肝素与肝素对大鼠内毒素诱导的实验性弥散性血管内凝血（DIC）的影响。静脉推注内毒素（10mg/kg）导致血小板计数、血浆纤维蛋白原、抗凝血酶III（AT-III）和肝素辅因子II水平逐渐下降，并且在注射后1至6小时纤维蛋白原/纤维蛋白降解产物水平升高，表明凝血和纤溶均被激活。在内毒素注射3小时后静脉给予达那肝素或肝素，可抑制内毒素诱导的血小板计数和血浆纤维蛋白原水平下降，也可抑制内毒素诱导的肾脏肾小球纤维蛋白沉积增加。观察到达那肝素与肝素在对血浆AT-III水平和凝血时间的影响方面存在差异。达那肝素显著抑制内毒素诱导的血浆AT-III水平下降和凝血酶原时间延长，而肝素对这些反应无影响。此外，达那肝素对内毒素诱导的活化部分凝血活酶时间延长的增强程度低于肝素。这些发现表明，达那肝素对内毒素诱导的血浆AT-III水平下降和凝血时间延长的作用比肝素更具优势。结果可能是由于达那肝素的抗Xa/抗凝血酶比率高于肝素，这表明达那肝素可能对DIC的治疗有用。
