Risk of Bleeding in Liver Cirrhosis Receiving Direct Oral Anticoagulants: A Systematic Review and Meta-analysis. 2023

Zhe Li, and Wentao Xu, and Le Wang, and Lu Chai, and Walter Ageno, and Fernando Gomes Romeiro, and Hongyu Li, and Xingshun Qi
Liver Cirrhosis Study Group, Department of Gastroenterology, General Hospital of Northern Theater Command, Shenyang, China.

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. CONCLUSIONS 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.

UI MeSH Term Description Entries
D008103 Liver Cirrhosis Liver disease in which the normal microcirculation, the gross vascular anatomy, and the hepatic architecture have been variably destroyed and altered with fibrous septa surrounding regenerated or regenerating parenchymal nodules. Cirrhosis, Liver,Fibrosis, Liver,Hepatic Cirrhosis,Liver Fibrosis,Cirrhosis, Hepatic
D006471 Gastrointestinal Hemorrhage Bleeding in any segment of the GASTROINTESTINAL TRACT from ESOPHAGUS to RECTUM. Hematochezia,Hemorrhage, Gastrointestinal,Gastrointestinal Hemorrhages,Hematochezias
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations
D000925 Anticoagulants Agents that prevent BLOOD CLOTTING. Anticoagulant Agent,Anticoagulant Drug,Anticoagulant,Anticoagulant Agents,Anticoagulant Drugs,Anticoagulation Agents,Indirect Thrombin Inhibitors,Agent, Anticoagulant,Agents, Anticoagulant,Agents, Anticoagulation,Drug, Anticoagulant,Drugs, Anticoagulant,Inhibitors, Indirect Thrombin,Thrombin Inhibitors, Indirect
D054556 Venous Thromboembolism Obstruction of a vein or VEINS (embolism) by a blood clot (THROMBUS) in the blood stream. Thromboembolism, Venous
D020246 Venous Thrombosis The formation or presence of a blood clot (THROMBUS) within a vein. Deep Vein Thrombosis,Phlebothrombosis,Thrombosis, Deep Vein,Thrombosis, Venous,Deep Venous Thrombosis,Deep-Vein Thrombosis,Deep-Venous Thrombosis,Deep Vein Thromboses,Deep Venous Thromboses,Deep-Vein Thromboses,Deep-Venous Thromboses,Phlebothromboses,Thromboses, Deep Vein,Thromboses, Deep Venous,Thromboses, Deep-Vein,Thromboses, Deep-Venous,Thromboses, Venous,Thrombosis, Deep Venous,Thrombosis, Deep-Vein,Thrombosis, Deep-Venous,Vein Thromboses, Deep,Vein Thrombosis, Deep,Venous Thromboses,Venous Thromboses, Deep,Venous Thrombosis, Deep
D020300 Intracranial Hemorrhages Bleeding within the SKULL, including hemorrhages in the brain and the three membranes of MENINGES. The escape of blood often leads to the formation of HEMATOMA in the cranial epidural, subdural, and subarachnoid spaces. Brain Hemorrhage,Hemorrhage, Intracranial,Posterior Fossa Hemorrhage,Brain Hemorrhages,Hemorrhage, Brain,Hemorrhage, Posterior Fossa,Hemorrhages, Brain,Hemorrhages, Intracranial,Hemorrhages, Posterior Fossa,Intracranial Hemorrhage,Posterior Fossa Hemorrhages

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