PB0548 - Efficacy of direct oral anticoagulants in liver cirrhosis: an in-vitro study

Monday, June 26, 2023

18:30 – 19:30 ET

Room: Exhibition

Presenting Author(s)

Cindy Pereira Portela, MD Student

MD student
Division and Central Laboratory of Hematology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
Lausanne, Vaud, Switzerland

Co-Author(s)

MZ

Maxime Grégoire G. Zermatten

Physician assistant
Division and Central Laboratory of Hematology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
Lausanne, Vaud, Switzerland
Debora Bertaggia Calderara, PhD

Research Associate
Division and Central Laboratory of Hematology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
Lausanne, Vaud, Switzerland
MF

Montserrat Fraga

Associate physician
Division of Gastroenterology and Hepatology, Lausanne University Hospital and University of Lausanne
Lausanne, Vaud, Switzerland
Alessandro Aliotta, PhD

Research Associate
Division and Central Laboratory of Hematology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
Lausanne, Vaud, Switzerland
Lucas Veuthey, BSc, MSc (he/him/his)

PhD student
Division and Central Laboratory of Hematology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
Lausanne, Vaud, Switzerland
Durre Shehwar, MSc MPhil

PhD Student
Department of Biochemistry, Quaid-i-Azam University, Islamabad, Pakistan
Islamabad, Islamabad, Pakistan
DM

Darius Moradpour

Physician in Chief, Full Professor
Division of Gastroenterology and Hepatology, Lausanne University Hospital and University of Lausanne
Lausanne, Vaud, Switzerland
LA

Lorenzo Alberio, MD (he/him/his)

Chief Physician, Associated Professor
Division and Central Laboratory of Hematology, Lausanne University Hospital (CHUV) and University of Lausanne, Lausanne, Switzerland
Lausanne, Vaud, Switzerland

Background: Liver cirrhosis (LC) induces alterations in haemostatic systems usually in favour of a prothrombotic state. Anticoagulation in LC-patients requires caution because of the unknown efficacy of the various anticoagulant drugs in this clinical context, unreliable monitoring and drug metabolism alterations.

Aims: To analyse the in vitro efficacy of direct oral anticoagulant drugs (DOAC: apixaban, edoxaban, rivaroxaban and dabigatran) in LC-patients.

Methods: Twenty-two LC-patients and 10 healthy donors were included (recruitment ongoing). Plasma samples were spiked with either Owren’s veronal buffer (vehicle), rivaroxaban, apixaban, edoxaban or dabigatran solutions (final target concentration: 150 ng/ml). DOAC concentrations were verified immediately before measuring ex vivo thrombin generation using ST Genesia with DrugScreen reagents (Stago, Asnières-sur-Seine, France). Ratios for velocity index (VI) and peak height (PH) assessed with and without DOAC were calculated and compared between LC-patients and controls using Mann-Whitney test.

Results: In apixaban treated LC-plasma, VI-ratio was significantly higher (0.42 vs. 0.27, p-value 0.0076) and PH-ratio slightly but also significantly higher [median 0.74 (cirrhotic) vs. 0.60 (controls), p-value 0.0329] compared to controls (Fig.1). For dabigatran and rivaroxaban, both ratios were significantly lower, respectively (0.58 vs. 0.80, p-value < 0.0001; 0.51 vs. 0.94, p-value < 0.0001); (0.49 vs. 0.69, p-value 0.0017; 0.14 vs. 0.31, p-value 0.003) in LC-plasma compared to controls. Both ratios did not significantly differ in edoxaban treated samples.

Conclusion(s): These preliminary data highlight a discordant anticoagulant effect of the various DOAC in normal versus LC-plasma. Edoxaban appears to exert a similar anticoagulant action, apixaban demonstrates a slightly lower anticoagulant potential, whereas dabigatran and rivaroxaban show a clearly higher anticoagulant effect in LC compared to control plasma. According to these in vitro pharmacodynamic observations and the in vivo pharmacokinetic characteristics in hepatic impairment, edoxaban seems to be the safest DOAC in LC-patients, followed by apixaban.