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Original Research |

Laboratory Assessment of the Anticoagulant Activity of Direct Oral Anticoagulants (DOACs): A Systematic Review

Bethany T. Samuelson, MD; Adam Cuker, MD; Deborah M. Siegal, MD; Mark Crowther, MD; David A. Garcia, MD
Author and Funding Information

Conflict of Interest

A.C. has served as a consultant for Amgen, Bracco, and Genzyme and has received research support from T2 Biosystems and Spark Therapeutics. DMS has participated in advisory boards for Boehringer Ingelheim, Dalichi Sankyo and Portola Pharmaceuticals. DAG has served as a consultant to BMS, Pfizer, Boehringer Ingelheim, Janssen and Dalichi Sankyo and served as an investigator to Janssen and Dalichi Sankyo. The remaining authors have no conflicts of interest to disclose.

Funding Information

This research was supported (in part) by the NHLBI under award number T32HL007093.

1Department of Medicine, Division of Hematology, University of Washington, 1959 NE Pacific St Seattle, WA 98195

2Department of Medicine and Department of Pathology & Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd Philadelphia, PA 19104

3Department of Medicine, McMaster University, 50 Charlton Avenue East, Hamilton, Ontario, Canada L8N 4A6

Corresponding Author Bethany T Samuelson 1100 Fairview Ave N D5-100 Seattle, WA 98109 .


Copyright 2016, . All Rights Reserved.


Chest. 2016. doi:10.1016/j.chest.2016.08.1462
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Abstract

Background  The direct oral anticoagulants (DOACs) are the treatment of choice for most patients with atrial fibrillation and/or non-cancer associated venous thromboembolic disease. While routine monitoring of these agents is not required, assessment of anticoagulant effect may be desirable in special situations. The objective of this study was to systematically review and summarize current evidence regarding laboratory assessment of the anticoagulant effects of dabigatran, rivaroxaban, apixaban and edoxaban.

Methods  Pubmed, Embase, and Web of Science were searched for studies reporting a relationship between drug levels and coagulation assay results.

Results  One hundred and twelve eligible studies were identified, including 35 for dabigatran, 50 for rivaroxaban, nine for apixaban and 13 for edoxaban. The performance of standard anticoagulation tests, including APTT and PT/INR, varied across both DOACs as well as reagents. For most assays, standard anticoagulation tests showed insufficient correlation to provide a reliable assessment of DOAC effects, including exclusion of clinically relevant drug levels. Dilute thrombin time assays demonstrated a high degree of linear correlation (r2 = 0.67-0.99) across a range of expected concentrations of dabigatran, as did ecarin-based assays. Calibrated anti-Xa assays demonstrated a high degree of linear correlation (r2 = 0.78-1.0) across a wide range of drug concentrations for rivaroxaban, apixaban and edoxaban.

Conclusions  Unfortunately, an ideal test, offering both accuracy and precision for measurement of any DOAC is not widely available. We recommend the use of a dilute thrombin time assay or ecarin-based assay for assessment of the anticoagulant effect of dabigatran and anti-Xa assays with drug-specific calibrators for assessment of the anticoagulant effects of direct Xa inhibitors. In the absence of these tests, thrombin time or APTT are recommended over PT/INR for assessment of dabigatran and PT/INR is recommended over APTT for detection of factor Xa inhibitors. Time since last dose, the presence or absence of drug interactions, renal and hepatic function should impact clinical estimates of anticoagulant effect in a patient for whom laboratory test results are not available.


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