Suzuki Akiko, Kaneko Makoto, Kanno Nobuko, Yatomi Yutaka
Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan.
Rinsho Byori. 2013 Jul;61(7):567-75.
Anticoagulant therapy is widely used for the prevention and treatment of thromboembolism. In addition to established agents such as warfarin, unfractionated heparin and low-molecular-weight heparins, a variety of new anticoagulant drugs has been introduced for clinical use, including direct thrombin inhibitors and factor Xa inhibitors. These new drugs can be given at fixed doses without the need for routine monitoring of the coagulation profile. However, an assays to evaluate anticoagulant strength would be valuable to prevent undesired hemorrhagic or thromboembolic events during treatment. In the present study, we examined the feasibility of several laboratory monitoring tests, including chromogenic-based anti-factor Xa assay and the thrombin generation test to determine the anticoagulant effect of low-molecular-weight heparins and fonda-parinux. Dose-dependent relationship between anti-factor Xa activity and the concentration of fondaparinux was observed by the chromogenic assays. In the thrombin generation test, the peak parameter seemed to be more informative than the endogenous thrombin potential, which corresponds to the total amount of thrombin activity, to assess the pharmacodynamic effects. In summary, our study suggested that both assays may be useful for quantitative determination of factor Xa activity. Further studies are necessary to develop and establish simpler methods that can be used in routine laboratory testing to monitor treatment with the newer anticoagulant drugs.
抗凝治疗广泛用于预防和治疗血栓栓塞。除了华法林、普通肝素和低分子肝素等已有的药物外,多种新型抗凝药物已被引入临床使用,包括直接凝血酶抑制剂和Xa因子抑制剂。这些新药可以固定剂量给药,无需常规监测凝血指标。然而,一种评估抗凝强度的检测方法对于预防治疗期间不期望的出血或血栓栓塞事件将是有价值的。在本研究中,我们检测了几种实验室监测试验的可行性,包括基于显色法的抗Xa因子检测和凝血酶生成试验,以确定低分子肝素和磺达肝癸钠的抗凝效果。通过显色法检测观察到抗Xa因子活性与磺达肝癸钠浓度之间存在剂量依赖性关系。在凝血酶生成试验中,对于评估药效学效应,峰值参数似乎比内源性凝血酶潜力(对应于凝血酶活性总量)更具信息量。总之,我们的研究表明这两种检测方法可能都有助于定量测定Xa因子活性。有必要进一步开展研究,开发并建立更简单的方法,用于常规实验室检测以监测新型抗凝药物的治疗。