Copyright
©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Bleeding prediction by rotational thromboelastometry in chronic hemodialysis patients with non-valvular atrial fibrillation on apixaban
Dimitra Bacharaki, Elias Kyriakou, Aggeliki Sardeli, Petros Nikolopoulos, George Triantaphyllis, Athina Drakou, Fotis Makris, Eleni Spanou, Eleni Triantou, Emmanouel Haviaras, Alexandra Fatourou, Aristarchos Poulis, Argyrios Tsantes, John Kyriazis, Sophia Lionaki
Dimitra Bacharaki, Aggeliki Sardeli, Petros Nikolopoulos, Sophia Lionaki, Clinical and Interventional Nephrology Unit, Attikon University General Hospital, Chaidari 12462, Attikí, Greece
Elias Kyriakou, Aristarchos Poulis, Argyrios Tsantes, Department of Laboratory Hematology, Hemostasis and Transfusion Services, Attikon University General Hospital, Chaidari 12462, Attikí, Greece
George Triantaphyllis, Emmanouel Haviaras, Hemodialysis Unit, Medifil AE Private Nephrological Centre, Peristeri 12132, Attikí, Greece
Athina Drakou, Eleni Triantou, Nephrology Unit, Henry Dunant Hospital Center, Athens 11526, Attikí, Greece
Fotis Makris, Alexandra Fatourou, Hemodialysis Unit, Mesogeios Palaiou Falirou, Palaio Faliro 17564, Attikí, Greece
Eleni Spanou, Hemodialysis Unit, Protypo Nephrology Center Piraeus, Piraeus 18454, Attikí, Greece
John Kyriazis, Department of Nephrology, General Hospital of Chios, Chios 82100, Chios Regional Unit, Greece
Author contributions: Bacharaki D and Kyriakou E participated in study design; Bacharaki D conceived the idea, drafted the manuscript and revised the manuscript for intellectual content; Kyriakou E, Poulis A, and Tsantes A performed lab analyses; Kyriakou E, Kyriazis J, and Lionaki S contributed to the writing of the manuscript; Sardeli A, Triantaphyllis G, Drakou A, Makris F, Spanou E, Triantou E, Haviaras E, Fatourou A participated in patient enrolment and collected clinical data; Nikolopoulos P contributed to the editing of tables and figures; Kyriazis J performed statistical analysis; Lionaki S revised the manuscript for language and intellectual content. All authors gave approval for the final version to be submitted.
Institutional review board statement: The study was reviewed and approved by the Attikon University General Hospital Institutional Review Board (Approval number 50/01-02-2021).
Informed consent statement: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: The data will be available upon reasonable request to the corresponding author.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Dimitra Bacharaki, MD, PhD Clinical and Interventional Nephrology Unit, Attikon University General Hospital, Rimini 1, Chaidari 12462, Attikí, Greece.
bacharaki@gmail.com
Received: July 17, 2025
Revised: August 18, 2025
Accepted: November 4, 2025
Published online: December 26, 2025
Processing time: 161 Days and 15.1 Hours
BACKGROUND
The use of apixaban in chronic hemodialysis (HD) patients for non-valvular atrial fibrillation (NVAF) is still controversial regarding benefit of stroke protection vs risk of bleeding. Rotational thromboelastometry (ROTEM) is a point of care method that evaluates clot formation in whole blood and has been used as an evaluation tool for bleeding risk assessment in non-HD apixaban users.
AIM
To determine whether bleeding risk can be predicted using ROTEM activated with tissue factor (EXTEM) in HD patients receiving apixaban for NVAF.
METHODS
Nineteen HD patients with NVAF treated with apixaban for at least 8 days were enrolled. Four dosing regimens were recorded as prescribed by their physician, from 2.5 mg once daily on a non-dialysis day to 5 mg twice daily. Standard coagulation tests, along with ROTEM and apixaban drug levels (using liquid anti-Xa assay) were performed once on a non-dialysis day before and two hours after apixaban morning pill administration. Patients were subsequently monitored for thrombotic/bleeding events and all-cause mortality.
RESULTS
Over a median follow-up period of 36 months, six patients experienced a bleeding event (group A) and 13 remained free of bleeding (group B). Six deaths were recorded: Three due to major bleeding, one from thrombotic stroke, and two unrelated to coagulopathy. EXTEM clotting time (CT)-post was the only parameter that significantly differed between group A and group B (P = 0.013). Each 1-second increase in CT-post was linked to an 8% higher likelihood of a bleeding event (odds ratio = 1.08, 95% confidence interval: 1.0-1.17; P = 0.048). A significant progressive increase was observed with the drug’s trough and peak levels (P < 0.05) across the four dosing regimens but no significant relationship was found between CT and apixaban dose groups.
CONCLUSION
Early detection of bleeding risk in HD patients with NVAF on Apixaban maybe be effectively achieved through frequent monitoring using ROTEM EXTEM post CT, thereby helping to reduce associated morbidity.
Core Tip: The clinical dilemma of anticoagulation choice in hemodialysis patients with non-valvular atrial fibrillation is still unresolved. Apixaban use yields so far conflicting results. We conducted a pilot study in hemodialysis patients with non-valvular atrial fibrillation on apixaban, where we measured once on a non-dialysis day drug levels and rotational thromboelastometry before and after the morning pill under the dosing regimen used in clinical practice. Then we registered bleeding and thrombotic events. We found that clotting time by rotational thromboelastometry EXTEM after the morning pill was associated with bleeding events and thus could potentially be used as a prediction tool.
