Presentation Details
| Investigating inter-assay variability between DOAC calibrated anti-factor Xa assays: A substudy of the PAUSE trial Ryan Baker1, Rita Selby2, 3, Karen A.Moffat4, 5, Melanie St John5, Alex C.Spyropoulos6, 7, 8, Sam Schulman9, James Douketis9. 1Temerty Faculty of Medicine, University of Toronto, Toronto, ON, Canada.2Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.3Department of Medicine, University of Toronto, Toronto, ON, Canada.4Hamilton Regional Laboratory Medicine Program, Hamilton, ON, Canada.5Department of Medicine, McMaster University, Hamilton, ON, Canada.6The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA.7Institute of Health System Science - The Feinstein Institutes for Medical Research, Manhasset, NY, USA.8Anticoagulation and Clinical Thrombosis Services, Northwell Health at Lenox Hill Hospital, New York, NY, USA.9Department of Medicine and Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, ON, Canada |
Abstract
BACKGROUND: Direct oral anticoagulants (DOACs), especially factor Xa inhibitors are first-line therapy for most indications due to their efficacy, safety and no requirement for routine monitoring. DOAC calibrated anti-Xa assays can accurately assess the residual anticoagulant level in patients requiring urgent procedures or surgery. However, previous studies have shown variability between anti-Xa levels determined by different reagent-instrument combinations. These studies had limitations such as using lyophilized plasma, DOAC-spiked plasma, or assayed at various laboratories which may explain the inter-assay variability. The PAUSE trial examined perioperative DOAC management for patients on chronic anticoagulation who had interrupted factor-Xa inhibitor therapy before undergoing elective surgery.[1] We conducted a substudy on frozen plasma samples from previously consented PAUSE trial patients. OBJECTIVES: 1. To describe the inter-assay variability in apixaban and rivaroxaban anti-Xa levels using three common coagulation reagent-instrument platforms. 2. To determine if any differences in anti-Xa levels between the reagent-instrument combinations would be clinically relevant. METHODS: We analyzed apixaban (n=76) and rivaroxaban (n=61) anti-Xa levels on 3 different reagent-instrument combinations using manufacturer specific reagents, calibrators and quality control material (STA® reagents on the STA CompactMAX (Diagnostica Stago), HemosIL on the ACL TOP 300 (Werfen) and Biophen (Hyphen Biomed) on the BCS XP (Siemens)). We analyzed inter-assay correlation as a group and at two pre-determined cut-offs (<30 ng/mL and >30 ng/mL). We also compared median anti-Xa levels across reagent-instrument combinations using analysis of variance. RESULTS: Both apixaban and rivaroxaban anti-Xa levels showed good to excellent correlation between the 3 reagent-instrument groups, with correlation coefficients (r) ranging from 0.74 – 0.95 for apixaban, and 0.64 – 0.92 for rivaroxaban in both the <30 ng/mL and >30 ng/mL groups. In a 3-way comparison of median anti-Xa levels there was no significant difference between the reagent-instrument combinations for either apixaban or rivaroxaban in the >30 ng/mL group (Figure 1). For anti-Xa activity levels <30 ng/mL, there was a significant difference between Biophen/BCS XP and HemosIL/ACL TOP for apixaban anti-Xa levels, and for rivaroxaban when comparing HemosIL/ACL TOP to both Biophen/BCS XP and Stago/STA CompactMAX (Figure 1). These differences were small and not clinically relevant. In 7.3% (10/136) samples, the three reagent-instrument combinations discrepantly classified anti-Xa levels across the 30 ng/mL threshold. CONCLUSIONS: Using plasma from patients who had interrupted factor-Xa inhibitor DOAC therapy we were able to demonstrate that anti-Xa levels determined by three of the most common reagent-instrument combinations correlate well with each other, when anti-Xa activity is <30 and >30 ng/mL. Although there are statistically significant differences between median anti-Xa levels in the <30 ng/mL group, particularly for rivaroxaban, these differences are small and not clinically significant and result in discrepant classification across the 30 ng/mL threshold in only 7.3% of samples. REFERENCES: 1. Douketis, J.D., et al., Perioperative Management of Patients With Atrial Fibrillation Receiving a Direct Oral Anticoagulant. JAMA Intern Med, 2019. 179(11): p.1469-1478.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.