TY - JOUR
T1 - Clinically relevant increases in the international normalized ratio and model of end-stage liver disease score by therapeutic doses of direct oral anticoagulants in patients with cirrhosis
AU - Lisman, Ton
AU - Bernal, William
AU - Adelmeijer, Jelle
AU - Kamphuisen, Pieter-Willem
AU - Bos, Sarah
AU - Porte, Robert J.
N1 - Funding Information: Funding information This study was funded by the departmental funds of T.L. Funding Information: This study was funded by departmental funds of T.L. Publisher Copyright: © 2023 The Author(s)
PY - 2023/1/1
Y1 - 2023/1/1
N2 - Background: Patients with cirrhosis are increasingly using direct oral anticoagulants (DOACs) in therapeutic doses for the treatment of portal vein thrombosis or for concomitant atrial fibrillation. DOACs may affect routine diagnostic tests of coagulation including the international normalized ratio (INR). The INR is a part of the model of end-stage liver disease (MELD) score, a validated score that predicts the mortality risk in patients with cirrhosis and is used to prioritize patients for liver transplantation. DOAC–induced increases in the INR may thus lead to artificial inflation of the MELD score. Objective: We studied the effect of DOACs on INR prolongation in patients with cirrhosis. Methods: We spiked plasma from 20 healthy individuals and 20 patients at the start of liver transplantation with DOACs in concentrations representing peak therapeutic levels. In addition, we studied INR increases in healthy controls and patients with mild cirrhosis who received the DOAC edoxaban for 1 week for study purposes. Results: In controls and patients, the INR increased by an ex vivo addition of a DOAC, and the INR increase in patients was proportional to the baseline INR values. The increase in INR translated to a median increase of between 3 and 10 MELD points, depending on the DOAC used. In controls and patients alike, the INR increased on the ingestion of edoxaban, which translated to an increase in 5 MELD points. Conclusions: Taken together, DOACs result in an INR increase that translates to clinically meaningful increases in MELD points in patients with cirrhosis, and precautions to avoid artificial inflation of the MELD score in these patients are warranted.
AB - Background: Patients with cirrhosis are increasingly using direct oral anticoagulants (DOACs) in therapeutic doses for the treatment of portal vein thrombosis or for concomitant atrial fibrillation. DOACs may affect routine diagnostic tests of coagulation including the international normalized ratio (INR). The INR is a part of the model of end-stage liver disease (MELD) score, a validated score that predicts the mortality risk in patients with cirrhosis and is used to prioritize patients for liver transplantation. DOAC–induced increases in the INR may thus lead to artificial inflation of the MELD score. Objective: We studied the effect of DOACs on INR prolongation in patients with cirrhosis. Methods: We spiked plasma from 20 healthy individuals and 20 patients at the start of liver transplantation with DOACs in concentrations representing peak therapeutic levels. In addition, we studied INR increases in healthy controls and patients with mild cirrhosis who received the DOAC edoxaban for 1 week for study purposes. Results: In controls and patients, the INR increased by an ex vivo addition of a DOAC, and the INR increase in patients was proportional to the baseline INR values. The increase in INR translated to a median increase of between 3 and 10 MELD points, depending on the DOAC used. In controls and patients alike, the INR increased on the ingestion of edoxaban, which translated to an increase in 5 MELD points. Conclusions: Taken together, DOACs result in an INR increase that translates to clinically meaningful increases in MELD points in patients with cirrhosis, and precautions to avoid artificial inflation of the MELD score in these patients are warranted.
KW - anticoagulants
KW - cirrhosis
KW - end-stage liver disease
KW - international normalized ratio
KW - liver transplantation
UR - http://www.scopus.com/inward/record.url?scp=85149289556&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.rpth.2023.100052
DO - https://doi.org/10.1016/j.rpth.2023.100052
M3 - Article
C2 - 36846648
SN - 2475-0379
VL - 7
JO - Research and practice in thrombosis and haemostasis
JF - Research and practice in thrombosis and haemostasis
IS - 1
M1 - 100052
ER -