Direct oral anticoagulants in cirrhosis: Rationale and current evidenceKeypoints
Cindy Pereira Portela,
Lucas A. Gautier,
Maxime G. Zermatten,
Montserrat Fraga,
Darius Moradpour,
Debora Bertaggia Calderara,
Alessandro Aliotta,
Lucas Veuthey,
Andrea De Gottardi,
Guido Stirnimann,
Lorenzo Alberio
Affiliations
Cindy Pereira Portela
Hemostasis and Platelet Research Laboratory, Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), CH-1010 Lausanne, Switzerland
Lucas A. Gautier
Hemostasis and Platelet Research Laboratory, Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), CH-1010 Lausanne, Switzerland
Maxime G. Zermatten
Hemostasis and Platelet Research Laboratory, Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), CH-1010 Lausanne, Switzerland; Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), CH-1010 Lausanne, Switzerland
Montserrat Fraga
Division of Gastroenterology and Hepatology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), CH-1010 Lausanne, Switzerland
Darius Moradpour
Division of Gastroenterology and Hepatology, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), CH-1010 Lausanne, Switzerland
Debora Bertaggia Calderara
Hemostasis and Platelet Research Laboratory, Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), CH-1010 Lausanne, Switzerland
Alessandro Aliotta
Hemostasis and Platelet Research Laboratory, Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), CH-1010 Lausanne, Switzerland
Lucas Veuthey
Hemostasis and Platelet Research Laboratory, Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), CH-1010 Lausanne, Switzerland
Andrea De Gottardi
Luzerner Kantonsspital, Lucerne, Switzerland; Gastroenterology and Hepatology, Ente Ospedaliero Cantonale, Lugano, Switzerland
Guido Stirnimann
University Clinic for Visceral Surgery and Medicine, University Hospital Inselspital and University of Bern, Bern, Switzerland
Lorenzo Alberio
Hemostasis and Platelet Research Laboratory, Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), CH-1010 Lausanne, Switzerland; Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), CH-1010 Lausanne, Switzerland; Corresponding author. Address: Division of Hematology and Central Hematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne (UNIL), CH-1010 Lausanne, Switzerland.
Summary: Cirrhosis is a major health concern worldwide with a complex pathophysiology affecting various biological systems, including all aspects of haemostasis. Bleeding risk is mainly driven by portal hypertension, but in end-stage liver disease it is further increased by alterations in haemostatic components, including platelet function, coagulation, and fibrinolysis. Concurrently, patients with cirrhosis are prone to venous thromboembolic events (VTE) because of the altered haemostatic balance, in particular an increase in thrombin generation. In patients with cirrhosis, vitamin K antagonists (VKA) and low molecular weight heparins (LMWH) are currently the standard of care for VTE prevention, with VKA also being standard of care for stroke prevention in those with atrial fibrillation. However, direct oral anticoagulants (DOAC) could have specific advantages in this patient population. Clinical experience suggests that DOAC are a safe and possibly more effective alternative to traditional anticoagulants for the treatment of VTE in patients with compensated cirrhosis. In addition, emerging data suggest that primary prophylactic treatment with anticoagulants may improve clinical outcomes in patients with cirrhosis by reducing the risk of hepatic decompensation. The selection of the most appropriate DOAC remains to be clarified. This review focuses on the rationale for the use of DOAC in patients with cirrhosis, the specific effects of the different DOAC (as assessed by in vitro and in vivo pharmacokinetic and pharmacodynamic studies), as well as clinical outcomes in patients with cirrhosis on DOAC.
