Lisman Ton, Bernal William, Adelmeijer Jelle, Kamphuisen Pieter-Willem, Bos Sarah, Porte Robert J
Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Res Pract Thromb Haemost. 2023 Jan 14;7(1):100052. doi: 10.1016/j.rpth.2023.100052. eCollection 2023 Jan.
Patients with cirrhosis are increasingly using direct oral anticoagulants (DOACs) in therapeutic doses for the treatment of portal vein thrombosis or for concomitant atrial fibrillation. DOACs may affect routine diagnostic tests of coagulation including the international normalized ratio (INR). The INR is a part of the model of end-stage liver disease (MELD) score, a validated score that predicts the mortality risk in patients with cirrhosis and is used to prioritize patients for liver transplantation. DOAC-induced increases in the INR may thus lead to artificial inflation of the MELD score.
We studied the effect of DOACs on INR prolongation in patients with cirrhosis.
We spiked plasma from 20 healthy individuals and 20 patients at the start of liver transplantation with DOACs in concentrations representing peak therapeutic levels. In addition, we studied INR increases in healthy controls and patients with mild cirrhosis who received the DOAC edoxaban for 1 week for study purposes.
In controls and patients, the INR increased by an addition of a DOAC, and the INR increase in patients was proportional to the baseline INR values. The increase in INR translated to a median increase of between 3 and 10 MELD points, depending on the DOAC used. In controls and patients alike, the INR increased on the ingestion of edoxaban, which translated to an increase in 5 MELD points.
Taken together, DOACs result in an INR increase that translates to clinically meaningful increases in MELD points in patients with cirrhosis, and precautions to avoid artificial inflation of the MELD score in these patients are warranted.
肝硬化患者越来越多地使用治疗剂量的直接口服抗凝剂（DOACs）来治疗门静脉血栓形成或并发的心房颤动。DOACs可能会影响包括国际标准化比值（INR）在内的常规凝血诊断测试。INR是终末期肝病模型（MELD）评分的一部分，该评分经过验证，可预测肝硬化患者的死亡风险，并用于确定肝移植患者的优先顺序。因此，DOACs导致的INR升高可能会导致MELD评分的人为升高。
我们研究了DOACs对肝硬化患者INR延长的影响。
我们在20名健康个体和20名肝移植开始时的患者的血浆中加入代表治疗峰值水平的DOACs。此外，我们研究了健康对照者和轻度肝硬化患者为研究目的接受DOAC依度沙班1周后的INR升高情况。
在对照组和患者中，加入DOAC后INR升高，患者的INR升高与基线INR值成正比。INR的升高转化为MELD评分中位数增加3至10分，具体取决于所使用的DOAC。在对照组和患者中，服用依度沙班后INR均升高，这转化为MELD评分增加5分。
综上所述，DOACs导致INR升高，这转化为肝硬化患者MELD评分有临床意义的增加，因此有必要采取预防措施以避免这些患者的MELD评分人为升高。
