2. Academic Validation
  3. Effect of direct oral anticoagulants in cirrhosis: an in vitro study

Effect of direct oral anticoagulants in cirrhosis: an in vitro study

  • J Thromb Haemost. 2025 Jun;23(6):1938-1952. doi: 10.1016/j.jtha.2025.03.011.
Cindy Pereira Portela 1,  Debora Bertaggia Calderara 1,  Elise Mdawar-Bailly 2,  Alessandro Aliotta 1,  Lucas Veuthey 1,  Lucas A Gautier 1,  Darius Moradpour 2,  Montserrat Fraga 2,  Maxime G Zermatten 1,  Lorenzo Alberio 3
Affiliations

Affiliations

  • 1 Haemostasis and Platelet Research Laboratory, Division of Haematology and Central Haematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland.
  • 2 Division of Gastroenterology and Hepatology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland.
  • 3 Haemostasis and Platelet Research Laboratory, Division of Haematology and Central Haematology Laboratory, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland. Electronic address: [email protected].
PMID: 40122463 DOI: 10.1016/j.jtha.2025.03.011
Abstract

Background: Cirrhosis is associated with a procoagulant state that may worsen disease evolution. Anticoagulation could be of particular interest in these patients. However, evidence on the use of direct oral anticoagulants (DOAC) in patients with cirrhosis is limited.

Objectives: Our aim was to explore the in vitro effect of DOAC on Thrombin generation (TG) in plasma from patients with cirrhosis compared to plasma from healthy controls.

Methods: Platelet-poor-plasma was obtained from patients with cirrhosis (n = 87; Child-Turcotte-Pugh class: A, n = 68; B, n = 14; C, n = 5) and controls (n = 17). TG was assessed with ST-Genesia analyzer. Plasma from patients with cirrhosis and thrombomodulin-mediated inhibition of endogenous Thrombin potential <20% (ThromboScreen) were defined as "highly procoagulant" (n = 36), ≥20% to 50% as "procoagulant" (n = 31), and >50% as "nonprocoagulant" (n = 20). Plasma samples were spiked with apixaban, edoxaban, rivaroxaban, or dabigatran at final concentrations of 50 and 150 ng/mL. TG was measured (DrugScreen) in plasma samples without and with DOAC.

Results: Apixaban, edoxaban, and rivaroxaban demonstrated significantly reduced inhibition of in vitro TG parameters in highly procoagulant plasma from patients with cirrhosis compared to plasma from controls, whereas possibly artifactual results were observed with dabigatran.

Conclusion: The anticoagulant potency of DOAC differs according to the individual procoagulant potential. Highly procoagulant plasma from patients with cirrhosis is less sensitive to the anticoagulant action of apixaban, edoxaban, and rivaroxaban than control plasma. These results, if confirmed in vivo, would support the concept of personalizing anticoagulant treatment in patients with a highly procoagulant state.

Keywords

DOAC; anticoagulation; cirrhosis; procoagulant potential; thrombin generation.

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