Academic Medical Center, Meibergdreef 9, Amsterdam, The Netherlands.
Thromb Haemost. 2013 Aug;110(2):223-32. doi: 10.1160/TH12-11-0803. Epub 2013 Jun 6.
Antithrombotic drugs like vitamin K antagonists and heparin have been the gold standard for the treatment and prevention of thromboembolic disease for many years. Unfortunately, there are several disadvantages of these antithrombotic drugs: they are accompanied by serious bleeding problems, it is necessary to monitor the therapeutic window, and there are various interactions with food and other drugs. This has led to the development of new oral anticoagulants, specifically inhibiting either thrombin or factor Xa. In terms of effectiveness, these drugs are comparable to the currently available anticoagulants; however, they are still associated with issues such as bleeding, reversal of the drug and complicated laboratory monitoring. Vitamin K antagonists, heparin, direct thrombin and factor Xa inhibitors have in common that they target key proteins of the haemostatic system. In an attempt to overcome these difficulties we investigated whether the intrinsic coagulation factors (VIII, IX, XI, XII, prekallikrein and high-molecular-weight kininogen) are superior targets for anticoagulation. We analysed epidemiological data concerning thrombosis and bleeding in patients deficient in one of the intrinsic pathway proteins. Furthermore, we discuss several thrombotic models in intrinsic coagulation factor-deficient animals. The combined results suggest that intrinsic coagulation factors could be suitable targets for anticoagulant drugs.
抗血栓药物，如维生素 K 拮抗剂和肝素，多年来一直是治疗和预防血栓栓塞性疾病的金标准。不幸的是，这些抗血栓药物存在一些缺点：它们伴随着严重的出血问题，需要监测治疗窗口，并且与食物和其他药物存在各种相互作用。这导致了新型口服抗凝剂的发展，特别是抑制凝血酶或因子 Xa 的药物。就有效性而言，这些药物与目前可用的抗凝剂相当；然而，它们仍然与出血、药物逆转和复杂的实验室监测等问题相关。维生素 K 拮抗剂、肝素、直接凝血酶和因子 Xa 抑制剂的共同点是它们靶向止血系统的关键蛋白。为了克服这些困难，我们研究了内在凝血因子（VIII、IX、XI、XII、激肽原和高分子量激肽原）是否是抗凝的更好靶点。我们分析了内在途径蛋白缺乏症患者血栓形成和出血的流行病学数据。此外，我们还讨论了内在凝血因子缺陷动物的几种血栓形成模型。综合结果表明，内在凝血因子可能是抗凝药物的合适靶点。
