Liver disease patients receiving DOAC treatment (ACLD: n = 104; vascular liver disease: n = 29) or vitamin K antagonists (VKA)/low-molecular-weight heparin (LMWH; ACLD: n = 45; vascular: n = 13) between January 2010 and September 2020 were retrospectively included. Invasive procedures and bleeding events were recorded. Calibrated anti-Xa peak levels and thrombomodulin-modified thrombin generation assays (TM-TGAs) were measured in a subgroup of 35/28 DOAC patients.
Among patients receiving DOAC, 55 (41.3%) had advanced liver dysfunction (Child-Pugh-stage [CPS] B/C) and 66 (49.6%) had experienced decompensation. Overall, 205 procedures were performed in 60 patients and procedure-related bleedings occurred in 7 (11.7%) patients. Additionally, 38 (28.6%) patients experienced spontaneous (15 minor, 23 major) bleedings during a median follow-up of 10.5 (IQR: 4.0-27.8) months. Spontaneous bleedings in ACLD patients were more common in CPS-B/C (at 12 months: 36.9% vs CPS-A: 15.9%, subdistribution hazard ratio [SHR]: 3.23 [95% CI: 1.59-6.58], P < .001), as were major bleedings (at 12 months: 22.0% vs 5.0%, SHR: 5.82 [95% CI: 2.00-16.90], P < .001). Importantly, CPS (adjusted SHR: 4.12 [91% CI: 1.82-9.37], P < .001), but not the presence of hepatocellular carcinoma or varices, was independently associated with major bleeding during DOAC treatment. Additionally, ACLD patients experiencing bleeding had worse overall survival (at 12 months: 88.9% vs 95.0% without bleeding; P < .001). Edoxaban anti-Xa peak levels were higher in patients with CPS-B/C (345 [95% CI: 169-395] vs CPS-A: 137 [95% CI: 96-248] ng/mL, P = .048) and were associated with lower TM-TGA. Importantly, spontaneous bleeding rates were comparable to VKA/LMWH patients.
Anticoagulants including DOACs should be used with caution in patients with advanced liver disease due to a significant rate of spontaneous bleeding events.
回顾性纳入2010年1月至2020年9月期间接受DOAC治疗(ACLD:n=104;血管性肝病:n=29)或维生素K拮抗剂(VKA)/低分子量肝素(LMWH;ACLD:n=45;血管:n=13)的肝病患者。记录侵入性程序和出血事件。在35/28名DOAC患者的亚组中测量了校准的抗Xa峰水平和血栓调节蛋白修饰的凝血酶生成测定(TM-TGA)。
在接受DOAC的患者中,55(41.3%)患有晚期肝功能障碍(Child-Pugh期[CPS]B/C),66(49.6%)患有代偿失调。总的来说,在60例患者中进行了205例手术,在7例(11.7%)患者中发生了与手术相关的出血。此外,38例(28.6%)患者经历了自发性(15例轻微,23个主要)出血,中位随访时间为10.5个月(IQR:4.0-27.8个月)。ACLD患者的自发性出血在CPS-B/C中更为常见(12个月时:36.9%vsCPS-A:15.9%,子分布危险比[SHR]:3.23[95%CI:1.59-6.58],P<.001),主要出血(12个月时:22.0%vs5.0%,SHR:5.82[95%CI:2.00-16.90],P<.001)。重要的是,CPS(调整后的SHR:4.12[91%CI:1.82-9.37],P<.001),但不是肝细胞癌或静脉曲张的存在,在DOAC治疗期间与大出血独立相关。此外,经历出血的ACLD患者总生存期较差(12个月时:88.9%vs无出血的95.0%;P<.001)。CPS-B/C患者的依多沙班抗Xa峰值水平较高(345[95%CI:169-395]vsCPS-A:137[95%CI:96-248]ng/mL,P=0.048),并与较低的TM-TGA相关。重要的是,自发性出血率与VKA/LMWH患者相当.
晚期肝病患者应谨慎使用包括DOAC在内的抗凝剂,因为自发性出血事件发生率显著。