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Comparison of the effect of the anti-Xa direct oral anticoagulants apixaban, edoxaban, and rivaroxaban on coagulation assays.
Int J Lab Hematol. 2016 Oct; 38(5):505-13.IJ

Abstract

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 SynthaSIL 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.

Authors+Show Affiliations

Pathology and Laboratory Medicine, UC Davis Health System, Sacramento, CA, USA. rcgosselin@ucdavis.edu.Laboratory Corporation of America, Burlington, NC, USA.Colorado Coagulation, Laboratory Corporation of America® Holdings, Englewood, CO, USA.

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

27265752

Citation

Gosselin, R, et al. "Comparison of the Effect of the anti-Xa Direct Oral Anticoagulants Apixaban, Edoxaban, and Rivaroxaban On Coagulation Assays." International Journal of Laboratory Hematology, vol. 38, no. 5, 2016, pp. 505-13.
Gosselin R, Grant RP, Adcock DM. Comparison of the effect of the anti-Xa direct oral anticoagulants apixaban, edoxaban, and rivaroxaban on coagulation assays. Int J Lab Hematol. 2016;38(5):505-13.
Gosselin, R., Grant, R. P., & Adcock, D. M. (2016). Comparison of the effect of the anti-Xa direct oral anticoagulants apixaban, edoxaban, and rivaroxaban on coagulation assays. International Journal of Laboratory Hematology, 38(5), 505-13. https://doi.org/10.1111/ijlh.12528
Gosselin R, Grant RP, Adcock DM. Comparison of the Effect of the anti-Xa Direct Oral Anticoagulants Apixaban, Edoxaban, and Rivaroxaban On Coagulation Assays. Int J Lab Hematol. 2016;38(5):505-13. PubMed PMID: 27265752.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparison of the effect of the anti-Xa direct oral anticoagulants apixaban, edoxaban, and rivaroxaban on coagulation assays. AU - Gosselin,R, AU - Grant,R P, AU - Adcock,D M, Y1 - 2016/06/06/ PY - 2016/02/10/received PY - 2016/04/18/accepted PY - 2016/6/7/entrez PY - 2016/6/7/pubmed PY - 2017/3/7/medline KW - APTT KW - Anti-Xa DOAC KW - PT KW - anticoagulants KW - assays KW - coagulation SP - 505 EP - 13 JF - International journal of laboratory hematology JO - Int J Lab Hematol VL - 38 IS - 5 N2 - 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 SynthaSIL 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. SN - 1751-553X UR - https://www.unboundmedicine.com/medline/citation/27265752/Comparison_of_the_effect_of_the_anti_Xa_direct_oral_anticoagulants_apixaban_edoxaban_and_rivaroxaban_on_coagulation_assays_ L2 - https://doi.org/10.1111/ijlh.12528 DB - PRIME DP - Unbound Medicine ER -