Interlaboratory Performance in Measurement of Dabigatran and Rivaroxaban

Authors

Oksana Volod, Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California
Marian Rollins-Raval, Department of Pathology, The University of New Mexico, Albuquerque
Andrew J. Goodwin, Department of Pathology, University of Vermont Medical Center, Burlington
Russell A. Higgins, Department of Pathology and Laboratory Medicine, University of Texas Health, San Antonio
Thomas Long, Biostatistics, College of American Pathologists, Northfield, Illinois
Wayne L. Chandler, Department of Pathology and Laboratory Medicine, Seattle Children's Hospital, Seattle, Washington
Neil SA Harris, Department of Pathology, University of Florida Health, Gainesville
Huy P. Pham, National Marrow Donor Program, Seattle Collection Center, Seattle, Washington
James Alexander Isom, Department of Pathology, University of South Florida Moffitt Cancer Center, Tampa
Karen Moser, Department of Pathology, University of Utah, Salt Lake City
John D. Olson, Department of Pathology and Laboratory Medicine, University of Texas Health, San Antonio
Kristi J. Smock, Department of Pathology, University of Utah, Salt Lake City
Amanda VanSandt, Department of Pathology, Oregon Health & Science University, Portland
Geoffrey Wool, Department of Pathology and Laboratory Medicine, University of Chicago, Chicago, Illinois
Dong Chen, Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota

Document Type

Article

Publication Date

1-2-2022

Abstract

CONTEXT.—: Assessing direct oral anticoagulant (DOAC) drug levels by reliable laboratory assays is necessary in a number of clinical scenarios.

OBJECTIVE.—: To evaluate the performance of DOAC-specific assays for various concentrations of dabigatran and rivaroxaban, assess the interlaboratory variability in measurement of these DOACs, and investigate the responsiveness of the routine clotting assays to various concentrations of these oral anticoagulants.

DESIGN.—: College of American Pathologists proficiency testing survey data from 2013 to 2016 were summarized and analyzed.

RESULTS.—: For dabigatran, the interlaboratory coefficient of variation (CV) of ecarin chromogenic assay was broad (ranging from 7.5% to 29.1%, 6.3% to 15.5%, and 6.8% to 9.0% for 100-ng/mL, 200-ng/mL, and 400-ng/mL targeted drug concentrations, respectively). The CV for diluted thrombin time for dabigatran was better overall (ranging from 11.6% to 17.2%, 9.3% to 12.3, and 7.1% to 11.2% for 100 ng/mL, 200 ng/mL, and 400 ng/mL, respectively). The rivaroxaban-calibrated anti-Xa assay CVs also showed variability (ranging from 11.5% to 22.2%, 7.2% to 10.9%, and 6.4% to 8.1% for 50-ng/mL, 200-ng/mL, and 400-ng/mL targeted drug concentrations, respectively). The prothrombin time (PT) and activated partial thromboplastin time (aPTT) showed variable dose- and reagent-dependent responsiveness to DOACs: PT was more responsive to rivaroxaban and aPTT to dabigatran. The undiluted thrombin time showed maximum prolongation across all 3 dabigatran concentrations, making it too sensitive for drug-level monitoring, but supporting its use as a qualitative screening assay.

CONCLUSIONS.—: DOAC-specific assays performed reasonably well. While PT and aPTT cannot be used safely to determine DOAC degree of anticoagulation, a normal thrombin time excludes the presence of dabigatran.

Recommended Citation

Volod O, Rollins-Raval M, Goodwin AJ, Higgins RA, Long T, Chandler WL, Harris NS, Pham HP, Isom JA, Moser K, Olson JD, Smock KJ, VanSandt A, Wool G, Chen D. Interlaboratory Performance in Measurement of Dabigatran and Rivaroxaban. Arch Pathol Lab Med. 2022 Jan 2;146(2):145-153. doi: 10.5858/arpa.2020-0633-CP. PMID: 34133726.