Review Article

The Safety of Anticoagulants and Antiplatelet Agents in Patients With Cirrhosis

Jiayi Ma; Naga P. Chalasani; Linus Schwantes-An; Einar Stefán Björnsson


Aliment Pharmacol Ther. 2023;57(1):52-71. 

In This Article

Abstract and Introduction


Patients with cirrhosis were long thought to be coagulopathic. However, this paradigm has changed in recent years and currently, cirrhosis is recognised as a prothrombotic state. Due to the increasing incidence of cirrhosis from nonalcoholic steatohepatitis which is closely associated with cardiac disease, patients with cirrhosis increasingly require therapy with anticoagulants and antiplatelet agents. However, their potential for causing catastrophic and life-threatening bleeding in patients with cirrhosis leads to hesitancy about their use in patients with cirrhosis. Overall, traditional anticoagulation is safe for all Child-Pugh classes while newer direct oral anticoagulants (DOACs) are mostly safe in Child-Pugh class A/B and contraindicated in severe hepatic impairment. For different indications, published data to date suggest that anticoagulation is overall safe for patients with cirrhosis who have venous thromboembolism, atrial fibrillation and portal vein thrombosis, and does not increase the risk of variceal bleeding. Moreover, DOACs appear to have similar safety profiles as traditional anticoagulants. Finally, most studies suggest that antiplatelet agents are also safe to use in patients with cirrhosis although they are mostly contraindicated in severe hepatic impairment. For both anticoagulants and antiplatelet agents, severe thrombocytopaenia presents a relative contraindication to their use. More prospective trials and large cohort studies are needed to advance our understanding of the safety and nuances of DOACs and antiplatelet agents in patients with advanced cirrhosis.


The alterations in the coagulation of patients with chronic liver disease and cirrhosis are complex. In early literature, these patients were considered auto-anticoagulated due to their prolonged prothrombin time, elevated International Normalised Ratio (INR) and thrombocytopenia. However, in recent years, the paradigm of haemostasis in cirrhosis has undergone many changes. Currently, cirrhosis is no longer considered just a state of coagulopathy, but also a prothrombotic state. In fact, studies have shown that patients with chronic liver disease and particularly those with cirrhosis are prone to develop thrombotic complications such as venous thromboembolism (VTE)[1] and portal vein thrombosis (PVT).[2] Furthermore, with the recent increase in the incidence and prevalence of nonalcoholic steatohepatitis (NASH) and its associated metabolic risk factors, many patients with cirrhosis develop atrial fibrillation (AF).[3] Thus, many patients with chronic liver disease and cirrhosis have important indications for anticoagulation.

Similarly, antiplatelet (AP) medications are more frequently used in patients with cirrhosis. With the increasing prevalence of nonalcoholic fatty liver disease (NAFLD) in the general population, the burden of cardiovascular comorbidities is also increasing in patients with chronic liver disease.[4] Whilst patients with cirrhosis were initially thought to be protected from coronary artery disease (CAD), recent studies have shown that patients with cirrhosis have a higher prevalence of CAD versus the general population.[5] In fact, underlying CAD is a major contributor to morbidity and mortality of liver transplant recipients.[6]

However, the potential for causing catastrophic and life-threatening bleeding in patients with cirrhosis leads to hesitancy about using anticoagulants including DOACs and AP agents in this population. Thus, it is of major importance to assess the safety profile of these drugs in patients who otherwise have appropriate clinical indications for these classes of medicines. In the following sections, we review current prescribing recommendations for different classes of anticoagulants and APs with a focus on hepatic impairment. The Child-Pugh score uses a combination of biochemical and clinical data to assess the severity of liver disease summarised as class A, B and C representing mild, moderate and severe hepatic impairment, respectively. We will also review the literature evaluating the safety of anticoagulants and AP agents in patients with cirrhosis for different clinical indications.