Diehl K H, Römisch J, Hein B, Jessel A, Ronneberger H, Pâques E P
Research Laboratories of Behringwerke AG, Marburg/Lahn, Germany.
Haemostasis. 1995 Jul-Aug;25(4):182-92. doi: 10.1159/000217159.
The specific thrombin inhibitor r-hirudin (HBW 023) has been demonstrated to be effective in preventing thrombosis in preclinical models. Up to now, no bleeding complications have been observed using therapeutically effective doses in animals studies. However, in case of inadvertent overdosing the occurrence of undesired impairment of coagulation cannot be excluded. As a potential antidote an activated prothrombin complex concentrate (APC) was tested on its ability to normalize blood coagulation. APC given s bolus injections 5 min and 3.0 mg/kg neutralized the r-hirudin-induced prolongation and 3.0 mg/kg neutralized the r-hirudin-induced prolongation of whole blood coagulation time in rabbits completely within 5 min without any clot formation in the blood vessels or capillaries of the heart, kidneys, or lungs. Furthermore, bleeding time prolongation induced by bolus application of 3.0 and 30.0 mg/kg r-hirudin was significantly inhibited by APC within 5 min. These results suggest that administration of APC may be an effective way to reverse the effects of r-hirudin in the coagulation system in case of inadvertent overdosing of r-hirudin.
特异性凝血酶抑制剂重组水蛭素（HBW 023）已在临床前模型中被证明对预防血栓形成有效。到目前为止，在动物研究中使用治疗有效剂量尚未观察到出血并发症。然而，在意外过量用药的情况下，不能排除发生不期望的凝血功能损害。作为一种潜在的解毒剂，测试了活化凝血酶原复合物浓缩物（APC）使凝血功能恢复正常的能力。在5分钟时静脉推注3.0mg/kg的APC可中和重组水蛭素诱导的兔全血凝固时间延长，且在5分钟内完全中和，心脏、肾脏或肺部的血管或毛细血管内无任何血栓形成。此外，静脉推注3.0和30.0mg/kg重组水蛭素诱导的出血时间延长在5分钟内被APC显著抑制。这些结果表明，在重组水蛭素意外过量用药的情况下，给予APC可能是逆转重组水蛭素在凝血系统中作用的有效方法。
