Investigating interassay variability between direct oral anticoagulant calibrated anti–factor Xa assays: a substudy of the perioperative anticoagulation use for surgery evaluation (PAUSE) trial

Background: Direct oral anticoagulant calibrated anti-factor Xa (FXa) assays can assess residual anticoagulant levels in patients requiring urgent procedures or surgery. However, previous studies have shown variability between anti-FXa levels determined by different instrument-reagent combinations....

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Main Authors: Ryan M. Baker, Rita Selby, Karen A. Moffat, Melanie St John, Alex C. Spyropoulos, Sam Schulman, James Douketis
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Research and Practice in Thrombosis and Haemostasis
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Online Access:http://www.sciencedirect.com/science/article/pii/S2475037925002237
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author Ryan M. Baker
Rita Selby
Karen A. Moffat
Melanie St John
Alex C. Spyropoulos
Sam Schulman
James Douketis
author_facet Ryan M. Baker
Rita Selby
Karen A. Moffat
Melanie St John
Alex C. Spyropoulos
Sam Schulman
James Douketis
author_sort Ryan M. Baker
collection DOAJ
description Background: Direct oral anticoagulant calibrated anti-factor Xa (FXa) assays can assess residual anticoagulant levels in patients requiring urgent procedures or surgery. However, previous studies have shown variability between anti-FXa levels determined by different instrument-reagent combinations. This may be related to use of lyophilized samples, direct oral anticoagulant-spiked plasma, or interlaboratory variation. Objectives: 1) Determine the interassay variability in anti-FXa levels using 3 common instrument-reagent combinations. 2) Determine if differences between these combinations are clinically relevant. Methods: Seventy apixaban and 59 rivaroxaban samples from participants in the Perioperative Anticoagulation Use for Surgery Evaluation trial were simultaneously tested using Biophen reagents on the BCS XP analyzer (Siemens), HemosIL reagents on the ACL TOP analyzer (Werfen), and Stago reagents on the STA CompactMAX analyzer (Diagnostica Stago). Interassay correlations were analyzed at the predetermined cutoff of 30 ng/mL and compared with median anti-FXa levels. Results: Anti-FXa levels showed moderate-to-very strong correlations for apixaban (r = 0.7271-0.9467) and rivaroxaban (r = 0.6531-0.9702). Anti-FXa levels were also significantly different between all instrument-reagent combinations in the < 30 ng/mL group. In the ≥ 30 ng/mL group, apixaban was significantly different in all combinations, while rivaroxaban only differed between Biophen/BCS XP and Stago/STA CompactMAX. 7.8% (10/129) of samples were discrepantly classified across the 30 ng/mL threshold. Conclusions: Anti-FXa levels determined by 3 common instrument-reagent combinations show moderate-to-very strong correlations with each other. Although there are statistically significant differences between median anti-FXa levels these differences are not clinically significant, and result in discrepant classification across the 30 ng/mL threshold in only 7.8% of samples.
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spelling doaj-art-101b07129f3d41d2981ce1c3bd2d28012025-08-20T04:01:56ZengElsevierResearch and Practice in Thrombosis and Haemostasis2475-03792025-05-019410289910.1016/j.rpth.2025.102899Investigating interassay variability between direct oral anticoagulant calibrated anti–factor Xa assays: a substudy of the perioperative anticoagulation use for surgery evaluation (PAUSE) trialRyan M. Baker0Rita Selby1Karen A. Moffat2Melanie St John3Alex C. Spyropoulos4Sam Schulman5James Douketis6Temerty Faculty of Medicine, University of Toronto, Ontario, CanadaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Ontario, Canada; Department of Medicine, University of Toronto, Ontario, Canada; Correspondence Rita Selby, Department of Laboratory Medicine and Pathobiology, University of Toronto Room 3EB-359C, Toronto General Hospital, 200 Elizabeth St, Toronto, Ontario, M5G 2C4, Canada.Hamilton Regional Laboratory Medicine Program, Ontario, Canada; Department of Medicine, McMaster University, Ontario, CanadaDepartment of Medicine, McMaster University, Ontario, CanadaThe Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA; Institute of Health System Science, The Feinstein Institutes for Medical Research, Manhasset, New York, USA; Anticoagulation and Clinical Thrombosis Services, Northwell Health at Lenox Hill Hospital, New York, New York, USADepartment of Medicine, McMaster University, Ontario, Canada; Thrombosis and Atherosclerosis Research Institute, McMaster University, Ontario, CanadaDepartment of Medicine, McMaster University, Ontario, Canada; Thrombosis and Atherosclerosis Research Institute, McMaster University, Ontario, CanadaBackground: Direct oral anticoagulant calibrated anti-factor Xa (FXa) assays can assess residual anticoagulant levels in patients requiring urgent procedures or surgery. However, previous studies have shown variability between anti-FXa levels determined by different instrument-reagent combinations. This may be related to use of lyophilized samples, direct oral anticoagulant-spiked plasma, or interlaboratory variation. Objectives: 1) Determine the interassay variability in anti-FXa levels using 3 common instrument-reagent combinations. 2) Determine if differences between these combinations are clinically relevant. Methods: Seventy apixaban and 59 rivaroxaban samples from participants in the Perioperative Anticoagulation Use for Surgery Evaluation trial were simultaneously tested using Biophen reagents on the BCS XP analyzer (Siemens), HemosIL reagents on the ACL TOP analyzer (Werfen), and Stago reagents on the STA CompactMAX analyzer (Diagnostica Stago). Interassay correlations were analyzed at the predetermined cutoff of 30 ng/mL and compared with median anti-FXa levels. Results: Anti-FXa levels showed moderate-to-very strong correlations for apixaban (r = 0.7271-0.9467) and rivaroxaban (r = 0.6531-0.9702). Anti-FXa levels were also significantly different between all instrument-reagent combinations in the < 30 ng/mL group. In the ≥ 30 ng/mL group, apixaban was significantly different in all combinations, while rivaroxaban only differed between Biophen/BCS XP and Stago/STA CompactMAX. 7.8% (10/129) of samples were discrepantly classified across the 30 ng/mL threshold. Conclusions: Anti-FXa levels determined by 3 common instrument-reagent combinations show moderate-to-very strong correlations with each other. Although there are statistically significant differences between median anti-FXa levels these differences are not clinically significant, and result in discrepant classification across the 30 ng/mL threshold in only 7.8% of samples.http://www.sciencedirect.com/science/article/pii/S2475037925002237apixabanblood coagulation testsclinical laboratory techniquesfactor Xa inhibitorsrivaroxaban
spellingShingle Ryan M. Baker
Rita Selby
Karen A. Moffat
Melanie St John
Alex C. Spyropoulos
Sam Schulman
James Douketis
Investigating interassay variability between direct oral anticoagulant calibrated anti–factor Xa assays: a substudy of the perioperative anticoagulation use for surgery evaluation (PAUSE) trial
Research and Practice in Thrombosis and Haemostasis
apixaban
blood coagulation tests
clinical laboratory techniques
factor Xa inhibitors
rivaroxaban
title Investigating interassay variability between direct oral anticoagulant calibrated anti–factor Xa assays: a substudy of the perioperative anticoagulation use for surgery evaluation (PAUSE) trial
title_full Investigating interassay variability between direct oral anticoagulant calibrated anti–factor Xa assays: a substudy of the perioperative anticoagulation use for surgery evaluation (PAUSE) trial
title_fullStr Investigating interassay variability between direct oral anticoagulant calibrated anti–factor Xa assays: a substudy of the perioperative anticoagulation use for surgery evaluation (PAUSE) trial
title_full_unstemmed Investigating interassay variability between direct oral anticoagulant calibrated anti–factor Xa assays: a substudy of the perioperative anticoagulation use for surgery evaluation (PAUSE) trial
title_short Investigating interassay variability between direct oral anticoagulant calibrated anti–factor Xa assays: a substudy of the perioperative anticoagulation use for surgery evaluation (PAUSE) trial
title_sort investigating interassay variability between direct oral anticoagulant calibrated anti factor xa assays a substudy of the perioperative anticoagulation use for surgery evaluation pause trial
topic apixaban
blood coagulation tests
clinical laboratory techniques
factor Xa inhibitors
rivaroxaban
url http://www.sciencedirect.com/science/article/pii/S2475037925002237
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