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Comparison of the effect of the anti‐Xa direct oral anticoagulants apixaban, edoxaban, and rivaroxaban on coagulation assays
Author(s) -
Gosselin R.,
Grant R. P.,
Adcock D. M.
Publication year - 2016
Publication title -
international journal of laboratory hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.705
H-Index - 55
eISSN - 1751-553X
pISSN - 1751-5521
DOI - 10.1111/ijlh.12528
Subject(s) - rivaroxaban , edoxaban , apixaban , chemistry , partial thromboplastin time , coagulation , anticoagulant , heparin , antithrombin , pharmacology , prothrombin time , dabigatran , chromatography , medicine , biochemistry , atrial fibrillation , warfarin
Summary Introduction The purpose of this study is to compare the effect of increasing concentrations of direct anti‐Xa oral anticoagulants ( DOAC ) apixaban‐, edoxaban‐, and rivaroxaban‐enriched plasma samples on various prothrombin time ( PT ), activated partial thromboplastin time ( APTT ), heparin calibrated anti‐Xa methods, and other coagulation assays. Methods Apixaban, edoxaban, or rivaroxaban was dissolved in dimethylsulfoxide and added to pooled normal plasma to obtain concentrations ranging from 0 ng/mL to approximately 600 ng/mL. The samples were tested using Innovin ® , Neoplastine ® CI Plus, Recombiplastin 2G, and Thromborel ® S for PT testing and Actin, Actin ® FS , Actin ® FSL , APTT ‐Automate, and Syntha SIL for APTT . Samples were also tested using four different anti‐Xa methods calibrated for unfractionated heparin or low molecular weight heparin. Special coagulation assays included antithrombin activity, lupus anticoagulant assays, and others. For special coagulation assays, the concentration of DOAC that resulted in a >15% change from baseline value was determined. DOAC quantification was performed using liquid chromatography–tandem mass spectrometry. Results All PT and APTT reagents demonstrated a higher sensitivity for edoxaban and rivaroxaban than for apixaban. Anti‐Xa methods were able to detect low concentrations of DOAC . DOACs effected special coagulation assays to differing degrees, with lupus anticoagulant testing using dilute viper venom, the most sensitive test to the presence of anti‐Xa DOAC . Conclusion No PT or APTT reagent system effectively detected apixaban. All anti‐Xa methods demonstrated sensitivity to low concentrations of DOAC . Dilute viper venom methods are exquisitely sensitive to anti‐Xa DOAC , suggesting potential use of this assay for screening or measuring these drugs.