Pereira Portela Cindy, Gautier Lucas A, Zermatten Maxime G, Fraga Montserrat, Moradpour Darius, Bertaggia Calderara Debora, Aliotta Alessandro, Veuthey Lucas, De Gottardi Andrea, Stirnimann Guido, Alberio Lorenzo
Hemostasis and Platelet Research Laboratory, Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), CH-1010 Lausanne, Switzerland.
Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), CH-1010 Lausanne, Switzerland.
JHEP Rep. 2024 May 9;6(8):101116. doi: 10.1016/j.jhepr.2024.101116. eCollection 2024 Aug.
Cirrhosis is a major health concern worldwide with a complex pathophysiology affecting various biological systems, including all aspects of haemostasis. Bleeding risk is mainly driven by portal hypertension, but in end-stage liver disease it is further increased by alterations in haemostatic components, including platelet function, coagulation, and fibrinolysis. Concurrently, patients with cirrhosis are prone to venous thromboembolic events (VTE) because of the altered haemostatic balance, in particular an increase in thrombin generation. In patients with cirrhosis, vitamin K antagonists (VKA) and low molecular weight heparins (LMWH) are currently the standard of care for VTE prevention, with VKA also being standard of care for stroke prevention in those with atrial fibrillation. However, direct oral anticoagulants (DOAC) could have specific advantages in this patient population. Clinical experience suggests that DOAC are a safe and possibly more effective alternative to traditional anticoagulants for the treatment of VTE in patients with compensated cirrhosis. In addition, emerging data suggest that primary prophylactic treatment with anticoagulants may improve clinical outcomes in patients with cirrhosis by reducing the risk of hepatic decompensation. The selection of the most appropriate DOAC remains to be clarified. This review focuses on the rationale for the use of DOAC in patients with cirrhosis, the specific effects of the different DOAC (as assessed by and pharmacokinetic and pharmacodynamic studies), as well as clinical outcomes in patients with cirrhosis on DOAC.
肝硬化是全球主要的健康问题，其病理生理过程复杂，会影响包括止血各方面在内的多种生物系统。出血风险主要由门静脉高压驱动，但在终末期肝病中，包括血小板功能、凝血和纤维蛋白溶解在内的止血成分改变会进一步增加出血风险。同时，由于止血平衡改变，尤其是凝血酶生成增加，肝硬化患者易发生静脉血栓栓塞事件（VTE）。在肝硬化患者中，维生素K拮抗剂（VKA）和低分子肝素（LMWH）目前是预防VTE的标准治疗方法，VKA也是房颤患者预防卒中的标准治疗方法。然而，直接口服抗凝剂（DOAC）在这一患者群体中可能具有特定优势。临床经验表明，对于代偿期肝硬化患者的VTE治疗，DOAC是传统抗凝剂的一种安全且可能更有效的替代方法。此外，新出现的数据表明，抗凝剂的一级预防性治疗可能通过降低肝失代偿风险来改善肝硬化患者的临床结局。最合适的DOAC的选择仍有待明确。本综述重点关注在肝硬化患者中使用DOAC的基本原理、不同DOAC的具体作用（通过药代动力学和药效学研究评估）以及使用DOAC的肝硬化患者的临床结局。
