肝硬化患者使用直接口服抗凝剂的出血风险：系统评价和荟萃分析。

Risk of Bleeding in Liver Cirrhosis Receiving Direct Oral Anticoagulants: A Systematic Review and Meta-analysis.

机构信息

Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China.

Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China.

出版信息

Thromb Haemost. 2023 Nov;123(11):1072-1088. doi: 10.1055/s-0043-1770100. Epub 2023 Jun 19.

DOI:10.1055/s-0043-1770100

PMID:37336474

Abstract

BACKGROUND

Direct oral anticoagulants (DOACs) are effective for the management of thromboembolic disorders. However, bleeding remains a major concern in cirrhotic patients receiving DOACs.

METHODS

PubMed, EMBASE, and Cochrane Library databases were searched. The incidence of bleeding episodes in cirrhotic patients receiving DOACs was pooled. Odds ratios (ORs) were calculated to compare the incidence of bleeding episodes in cirrhotic patients who received DOACs versus those who received conventional anticoagulants and did not receive anticoagulants.

RESULTS

Twenty-nine studies were included. All bleeding, major bleeding, fatal bleeding, gastrointestinal bleeding, and intracranial hemorrhage episodes were observed in 310/2,469, 100/1,388, 2/611, 166/1,886, and 5/1,147 cirrhotic patients receiving DOACs, respectively. Their pooled incidences were 13, 6, 0, 8, and 0%, respectively. They became higher in subgroup analyses of studies with advanced age, a longer treatment duration, and Child-Turcotte-Pugh class C. Compared with conventional anticoagulants, DOACs were associated with lower incidences of all bleeding (OR = 0.71, 95% confidence interval [CI] = 0.52-0.98) and major bleeding (OR = 0.55, 95% CI = 0.37-0.83) in cirrhotic patients, but not those of fatal bleeding (OR = 0.21, 95% CI = 0.04-1.28), gastrointestinal bleeding (OR = 0.78, 95% CI = 0.52-1.17), or intracranial hemorrhage (OR = 0.36, 95% CI = 0.12-1.12). The incidences of all bleeding (OR = 1.04, 95% CI = 0.22-4.79) and major bleeding (OR = 0.96, 95% CI = 0.26-3.61) did not significantly differ between cirrhotic patients with portal vein thrombosis (PVT) who received DOACs and those who did not receive anticoagulants.

CONCLUSION

DOACs carry a low risk of bleeding in liver cirrhosis. Age, treatment duration, and Child-Turcotte-Pugh class may be associated with bleeding in cirrhotic patients receiving DOACs. The risk of bleeding is not increased by DOACs in cirrhotic patients with PVT.

摘要

背景

直接口服抗凝剂（DOACs）在血栓栓塞性疾病的管理中具有疗效。然而，在接受 DOACs 的肝硬化患者中，出血仍然是一个主要关注点。

方法

检索了 PubMed、EMBASE 和 Cochrane 图书馆数据库。汇总了接受 DOACs 的肝硬化患者出血事件的发生率。计算比值比（ORs）以比较接受 DOACs 的肝硬化患者与接受传统抗凝剂且未接受抗凝剂的患者出血事件的发生率。

结果

纳入了 29 项研究。在接受 DOACs 的 310/2469、100/1388、2/611、166/1886 和 5/1147 例肝硬化患者中，分别观察到所有出血、大出血、致命性出血、胃肠道出血和颅内出血事件。它们的合并发生率分别为 13%、6%、0%、8%和 0%。在年龄较大、治疗时间较长和 Child-Turcotte-Pugh 分级为 C 的研究亚组分析中，这些发生率更高。与传统抗凝剂相比，DOACs 与肝硬化患者的所有出血（OR=0.71，95%置信区间[CI]0.52-0.98）和大出血（OR=0.55，95%CI0.37-0.83）的发生率较低，但致命性出血（OR=0.21，95%CI0.04-1.28）、胃肠道出血（OR=0.78，95%CI0.52-1.17）或颅内出血（OR=0.36，95%CI0.12-1.12）的发生率无显著差异。在接受 DOACs 的伴有门静脉血栓形成（PVT）的肝硬化患者与未接受抗凝剂的患者中，所有出血（OR=1.04，95%CI0.22-4.79）和大出血（OR=0.96，95%CI0.26-3.61）的发生率无显著差异。