Hartung K, Meyer F, Bock F, Isermann B
Institut für Klinische Chemie und Pathobiochemie, Otto-von-Guericke-Universität Magdeburg, Deutschland.
Klinik für Allgemein-, Viszeral- & Gefäßchirurgie, Universitätsklinikum Magdeburg A. ö. R., Deutschland.
Zentralbl Chir. 2014 Feb;139(1):89-97. doi: 10.1055/s-0032-1328004. Epub 2013 Mar 4.
Regarding anticoagulant therapies there has been a remarkable shift in recent years. The objective of this brief overview is to provide relevant information and guidelines on the advantages and disadvantages of novel anticoagulants addressing specifically the surgical disciplines. Hitherto, conventional anticoagulant therapy in patients with a high thrombosis risk was largely limited to heparins and vitamin-K antagonists (VKA). Their modes of action, the difficulties in managing VKAs (e.g., bridging therapy) and the risk of HIT (heparin-induced thrombocytopenia) associated with heparins are briefly discussed. Novel anticoagulants supposedly eliminate these obstacles. Fondaparinux (Arixtra®) is a fully synthetic pentasaccharide which acts like a heparin but has an increased half life. Fondaparinux has a diminished risk of HIT. However, no specific antidote is currently available for Fondaparinux. The novel oral anticoagulants (NOAC) dabigatran etexilat (Pradaxa®), rivaroxaban (Xarelto®) and apixaban (Eliquis®), also known as "direct" anticoagulants, act independently from antithrombin by inhibiting thrombin, as in the case of dabigatran, or by inhibiting factor Xa, as in the case of rivaroxaban and apixaban. It is assumed that they are suitable for long-term use and do not require laboratory monitoring. Nevertheless, clinical experience is very limited and caution rather than quick conclusions is necessary. Two major drawbacks are on the one hand the risk of drug accumulation in kidney and/or liver disease and, on the other hand, the lack of specific antidotes. In addition, interactions with other medication may have unexpected effects on serum drug levels. Therefore, the analysis of drug levels in the plasma may become necessary in subgroups of patients.
Studies establishing clear recommendations for the desirable and measurable reference range are needed. Similarly, evidence-based recommendations regarding perioperative prevention of thrombosis are required ("bridging": yes or no?). Irrespective of these issues, the authors predict a further expansion of the use of NOACs.
近年来,抗凝治疗领域发生了显著变化。本简要概述的目的是提供有关新型抗凝剂优缺点的相关信息和指南,特别针对外科领域。迄今为止,血栓形成风险高的患者的传统抗凝治疗主要限于肝素和维生素K拮抗剂(VKA)。简要讨论了它们的作用方式、VKA管理中的困难(如桥接治疗)以及与肝素相关的肝素诱导的血小板减少症(HIT)风险。新型抗凝剂据称消除了这些障碍。磺达肝癸钠(安卓)是一种完全合成的五糖,其作用类似于肝素,但半衰期延长。磺达肝癸钠发生HIT的风险降低。然而,目前尚无针对磺达肝癸钠的特异性解毒剂。新型口服抗凝剂(NOAC)达比加群酯(Pradaxa)、利伐沙班(拜瑞妥)和阿哌沙班(艾乐妥),也被称为“直接”抗凝剂,通过抑制凝血酶(如达比加群的情况)或抑制Xa因子(如利伐沙班和阿哌沙班的情况)独立于抗凝血酶发挥作用。据推测,它们适用于长期使用且无需实验室监测。然而,临床经验非常有限,需要谨慎而非仓促下结论。两个主要缺点一方面是在肾脏和/或肝脏疾病中药物蓄积的风险,另一方面是缺乏特异性解毒剂。此外,与其他药物的相互作用可能对血清药物水平产生意想不到的影响。因此,在某些患者亚组中可能需要分析血浆中的药物水平。
需要开展研究以建立关于理想和可测量参考范围的明确建议。同样,需要有关于围手术期血栓形成预防的循证建议(“桥接”:是或否?)。无论这些问题如何,作者预测NOAC的使用将进一步扩大。