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Thromb Haemost 2023; 123(11): 1072-1088
DOI: 10.1055/s-0043-1770100
Stroke, Systemic or Venous Thromboembolism

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

Zhe Li   *
1   Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
2   Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
,
Wentao Xu   *
1   Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
2   Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
,
Le Wang   *
1   Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
3   Postgraduate College, China Medical University, Shenyang, China
,
Lu Chai   *
1   Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
2   Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
,
Walter Ageno
4   Department of Medicine and Surgery, University of Insubria, Varese, Italy
,
Fernando Gomes Romeiro
5   Department of Internal Medicine, Botucatu Medical School, São Paulo State University (UNESP), São Paulo, Brazil
,
Hongyu Li
1   Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
2   Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
3   Postgraduate College, China Medical University, Shenyang, China
,
Xingshun Qi
1   Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China
2   Department of Life Sciences and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China
3   Postgraduate College, China Medical University, Shenyang, China
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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.

Keywords

liver cirrhosis - DOACs - thrombosis - bleeding

Authors' Contribution

Conception and design: Z. L. and X. Q.; Collection and assembly of data: Z. L., W. X., and L. C.; Data analysis and interpretation: Z. L., W. X., L. W., L. C., and X. Q.; manuscript writing: Z. L., W. X., L. W., L. C., and X. Q.; Final approval of manuscript: Z. L., W. X., L. W., L. C., W. A., F. G. R., H. L., and X. Q.; Supervision: X. Q. All authors have made an intellectual contribution to the manuscript and approved the submission.


* Co-first authors.


Supplementary Material



Publication History

Received: 16 March 2023

Accepted: 12 May 2023

Article published online:
19 June 2023

© 2023. Thieme. All rights reserved.

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