Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Semin Liver Dis. 2019 May;39(2):195-208. doi: 10.1055/s-0039-1679934. Epub 2019 Apr 12.
Direct-acting oral anticoagulants (DOACs) have provided benefit in patients requiring anticoagulation for certain diseases by decreasing the burden of subcutaneous injections and the requirement for frequent monitoring through regular blood tests, to ensure adequacy of the therapeutic doses. Studies have demonstrated DOACs to be as safe, and in some instance safer, compared with traditional anticoagulants in the general population. However, the studies evaluating DOACs excluded patients with cirrhosis, a condition associated with an increased risk of developing portal vein thrombosis (PVT). Warfarin or low-molecular weight heparin are the standard-of-care treatment for acute PVT in cirrhosis, although there is enthusiasm in a paradigm shift switching to DOACs for the treatment of acute PVT in cirrhosis, particularly since the release of DOAC antidotes. This article reviews the current Food and Drug Administration-approved DOACs, hepatic metabolism of DOACs, pharmacokinetics of DOACs in patients with cirrhosis, safety of DOACs (including bleeding, hepatotoxicity, and pregnancy), current treatment guidelines for PVT in cirrhosis, and studies evaluating the use of DOACs in cirrhosis and for the treatment of PVT in cirrhosis. The potential use of DOACs for PVT primary prophylaxis in at-risk patients with cirrhosis and the possible antifibrotic effects of DOACs are also discussed.
直接口服抗凝剂(DOACs)通过减少皮下注射的负担和通过定期血液检查来确保治疗剂量的充分性,减少了对某些疾病需要抗凝的患者的负担,同时也减少了对频繁监测的需求。研究表明,与普通人群中的传统抗凝剂相比,DOACs 在安全性方面具有同等甚至更优的效果。然而,评估 DOACs 的研究排除了患有肝硬化的患者,肝硬化与发生门静脉血栓形成(PVT)的风险增加有关。华法林或低分子量肝素是肝硬化急性 PVT 的标准治疗方法,尽管人们热衷于将 DOACs 作为肝硬化急性 PVT 的治疗方法进行范式转变,特别是在 DOAC 解毒剂问世之后。本文回顾了目前获得美国食品和药物管理局批准的 DOACs、DOACs 的肝脏代谢、肝硬化患者中 DOACs 的药代动力学、DOACs 的安全性(包括出血、肝毒性和妊娠)、肝硬化 PVT 的当前治疗指南,以及评估 DOACs 在肝硬化中的应用和治疗肝硬化 PVT 的研究。还讨论了 DOACs 在有风险的肝硬化患者中用于 PVT 一级预防的潜在用途,以及 DOACs 的可能抗纤维化作用。