Incidence and Outcomes of Thromboembolic and Bleeding Events in Patients With Liver Cirrhosis in the USA

Xiaoquan Huang; Marwan S. Abougergi; Chenyu Sun; Dermot Murphy; Vikram Sondhi; Bing Chen; Xin Zheng; Shiyao Chen; Yichen Wang


Liver International. 2023;43(2):434-441. 

In This Article

Abstract and Introduction


Background & Aims: Understanding the epidemiology of bleeding and thromboembolism (clotting) in liver cirrhosis provides important data for future studies and policymaking; however, head-to-head comparisons of bleeding and clotting remain limited.

Methods: This is a populational retrospective cohort study using the US National Readmission Database of 2018 to compare the incidence and outcomes of bleeding and clotting events in patients with liver cirrhosis. The primary outcomes were the 11-month incidence proportion of bleeding and clotting events.

Results: Of 1 304 815 participants, 26 569 had liver cirrhosis (45.0% women, mean age 57.2 [SD, 12.7] years). During the 11-month follow-up, in patients with cirrhosis, for bleeding and clotting events, the incidence proportions was 15.3% and 6.6%; the risk-standardized all-cause mortality rates were 2.4% and 1.0%; the rates of intensive care intervention were 4.1% and 1.9%; the rates of rehabilitation transfer were .2% and .2%; the cumulative length of stays were 45 100 and 23 566 days; total hospital costs were 147 and 84 million US dollars; total hospital charges were 620 and 365 million US dollars. Compared to non-cirrhosis, liver cirrhosis was associated with higher rates of bleeding (adjusted hazard ratio, 3.02 [95% CI, 2.85–3.20]) and portal vein thrombosis (PVT) (18.46 [14.86–22.92]), and slightly lower risks of other non-PVT venous thromboembolic events (.82 [.75–.89]).

Conclusions: Bleeding is more common than thromboembolism in patients with liver cirrhosis, causes higher morbidity, mortality and resource utilization. Liver cirrhosis is an independent risk factor for bleeding and PVT, but not non-PVT thromboembolism including venous thromboembolism, acute myocardial infarction and ischemic stroke.


The progression of cirrhosis is accompanied by hepatic synthetic dysfunction with resulting underproduction of clotting and antithrombotic proteins. As a result, patients with liver cirrhosis might develop thromboembolic (clotting) or bleeding tendencies based on the relative levels of protein groups.[1,2] Gastroesophageal variceal bleeding is one of the most feared complications of decompensated cirrhosis.[3] Non-variceal upper gastrointestinal bleeding events also increase in this setting, including bleeding from ulcers, esophagitis/gastritis and portal hypertensive gastropathy. On the other hand, patients with liver cirrhosis are also at risk of clotting events despite an elevated prothrombin time and international normalized ratio (INR). In this setting, antithrombotic proteins are produced at levels lower than those of the clotting cascade, an event that cannot be detected on blood tests. As a result, portal vein thrombosis (PVT) occurs in approximately 20% of patients with liver cirrhosis and occurs even more frequently after liver decompensation.[4] In addition, other non-splanchnic thromboses, comprising deep venous thrombosis (DVT), pulmonary embolism, cardiovascular risk factors, and ischemic stroke, are also not uncommon among patients with liver cirrhosis.[5]

Thromboembolic events among patients with liver cirrhosis present a treatment conundrum. The risk of pulmonary embolism or propagation of the clot locally should be weighed against the risk of massive bleeding, especially in the presence of oesophageal varices. The one-year variceal bleeding recurrent rate is approximately 60%,[6] and bleeding from gastric and oesophageal varices is the leading cause of death in cirrhosis, with a mortality rate of around 15–20% at six weeks.[7] On the other hand, untreated PVT, DVT, or coronary artery occlusion might also have severe consequences, including cirrhosis progression, pulmonary embolus and myocardial infarction.[2,8,9]

In recent decades, especially after the widespread use of anticoagulation driven partly by the advent of new anticoagulation agents that do not require laboratory monitoring, contradictory results were obtained concerning anticoagulation among patients with advanced cirrhosis. Some small observational studies showed that anticoagulation in this setting is safe and significantly reduces the risk of PVT development, liver decompensation[10] and markedly improving liver function.[11] However, other recent studies indicate that anticoagulation therapy in the setting of liver cirrhosis and secondary oesophageal varices is associated with an increased risk of variceal bleeding.[12]

A few epidemiology studies have looked at bleeding and clotting separately, but none has compared these two disorders head to head.[5,13,14] Given this background, the current study aimed to use the largest readmission database in the USA to analyse the incidence of clotting and bleeding events among patients with liver cirrhosis and compare their outcomes, including mortality, morbidity and resource utilization.