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Assessment of direct oral anticoagulant assay use in clinical practice

  • Tina M. GuEmail author
  • David A. Garcia
  • Daniel E. Sabath
Article

Abstract

There are no clear and consistent guidelines on how to utilize DOAC assays, and reports on the use of DOAC levels in clinical practice is limited. The objective of this study was to analyze why DOAC levels are ordered, how the results affect clinical decision-making, and to determine if DOAC assays are utilized appropriately. This was a retrospective chart review study analyzing 150 dabigatran, rivaroxaban, and apixaban levels performed at a single institution. The majority of DOAC assays were ordered in situations or special patient populations where confirming absence or detecting presence of drug may be useful. The most common indication for ordering assays was prior to an invasive procedure. Most DOAC levels were timed appropriately but peak levels were most likely to be incorrectly ordered. Clinical decisions following level results depended on indication for ordering and were most commonly used to determine whether or not to proceed with an invasive procedure. The results of our study suggest while DOAC assays are generally ordered for useful indications, there is still a lack of understanding of when levels should be drawn and how to interpret DOAC assay results.

Keywords

Anticoagulant agents Dabigatran Rivaroxaban Apixaban Drug monitoring 

Notes

Acknowledgements

We would like to acknowledge Ann K. Wittkowsky, PharmD, CACP, FASHP, FCCP, retired Director of Anticoagulation Services at University of Washington Medical Center for her thoughtful comments and help with earlier versions of this manuscript.

Author contributions

TMG, DAG, and DES designed the study. TMG generated the data. TMG, DAG, and DES interpreted the results. TMG drafted the manuscript. DAG and DES critically revised the manuscript.

Compliance with ethical standards

Conflict of interest

T. M. Gu and D. E. Sabath declare they have no conflict of interests. D. A. Garcia has received research support from Daiichi Sankyo and consulting fees from Janssen.

Ethical approval

This was a retrospective study approved by the institutional review board at University of Washington Medicine. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

For this type of study formal consent is not required.

Supplementary material

11239_2018_1793_MOESM1_ESM.tiff (1.1 mb)
Supplementary Fig. 1 Clinical decisions following assay results in the setting of acute hemorrhage. The following decisions refer to changes made at discharge: restarted DOAC, discontinued DOAC, and switched anticoagulant. (TIFF 1142 KB)
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Supplementary Fig. 2 Clinical decisions following assay results in the setting of acute thrombosis. (TIFF 1142 KB)
11239_2018_1793_MOESM3_ESM.tiff (1.1 mb)
Supplementary Fig. 3 Clinical decisions following assay results for drug interaction or renal impairment. (TIFF 1142 KB)
11239_2018_1793_MOESM4_ESM.docx (17 kb)
Supplementary material 4 (DOCX 16 KB)
11239_2018_1793_MOESM5_ESM.docx (16 kb)
Supplementary material 5 (DOCX 16 KB)

References

  1. 1.
    Barnes GD, Lucas E, Alexander GC, Goldberger ZD (2015) National trends in ambulatory oral anticoagulant use. Am J Med 128:1300–1305CrossRefGoogle Scholar
  2. 2.
    Cuker A, Siegal D (2015) Monitoring and reversal of direct oral anticoagulant. Hematology 2015:117–124CrossRefGoogle Scholar
  3. 3.
    Samuelson B, Cuker A, Siegal D, Crowther M, Garcia DA (2017) Laboratory assessment of the anticoagulant activity of direct oral anticoagulants. Chest 151:127–138CrossRefGoogle Scholar
  4. 4.
    Adcock DM, Gosselin R (2015) Direct oral anticoagulants in the laboratory: 2015 review. Thromb Res 136:7–12CrossRefGoogle Scholar
  5. 5.
    Mueck W, Borris LC, Dahl OE, Haas S, Huisman MV, Kakkar AK, Kalebo P, Muelhofer E, Misselwitz F, Eriksson BI (2008) Population pharmacokinetics and pharmacodynamics of once- and twice-daily rivaroxaban for the prevention of venous thromboembolism in patients undergoing total hip replacement. Thromb Haemost 100:453–461CrossRefGoogle Scholar
  6. 6.
    Buller HR, Lensing AW, Prins MH, Agnelli G, Cohen A, Gallus AS, Misselwitz F, Raskob G, Schellong S, Segers A (2008) A dose-ranging study evaluating once-daily oral administration of the factor Xa inhibitor rivaroxaban in the treatment of patients with acute symptomatic deep vein thrombosis: the Einstein DVT Dose Ranging Study. Blood 112:2242–2247CrossRefGoogle Scholar
  7. 7.
    van Ryn J, Stangler J, Haertter S, Liesenfeld KH, Wienen W, Feuring M, Clemens A (2010) Dabigatran etexilate—a novel reversible oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity. Thromb Haemost 103:1116–1127CrossRefGoogle Scholar
  8. 8.
    Eliquis - Summary of Product Characteristics (2017) http://www.ema.europa.eu/docs/ en_GB/document_library/EPAR_-_Product_Information/human/002148/WC500107728.pdf. Accessed 24 Aug 2017
  9. 9.
    Wright C, Brown R, Cuker A (2017) Laboratory measurement of the direct oral anticoagulants: indications and impact on management in clinical practice. Int J Lab Hematol 39:31–36CrossRefGoogle Scholar
  10. 10.
    Martin K, Moll S (2016) Direct oral anticoagulant drug level testing in clinical practice: a single institution experience. Thromb Res 143:40–44CrossRefGoogle Scholar
  11. 11.
    Healey JS, Eikelboom J, Douketis J, Wallentin L, Oldgren J, Yang S, Themeles E, Heidbuchel H, Avezum A, Reilly P, Connolly SJ, Yusuf S, Ezekowitz M (2012) Periprocedural bleeding and thromboembolic events with dabigatran compared with warfarin: results from the randomized evaluation of long-term anticoagulation therapy (RE-LY) randomized trial. Circulation 126:343–348CrossRefGoogle Scholar
  12. 12.
    Sherwood MW, Douketis JD, Patel MR, Piccini JP, Hellkamp AS, Lokhnygina Y, Spyropoulos AC, Hankey GJ, Singer DE, Nessel CC, Mahaffey KW, Fox KA, Califf RM, Becker RC (2014) Outcomes of temporary interruption of rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: results from the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation (ROCKET AF). Circulation 129:1850–1859CrossRefGoogle Scholar
  13. 13.
    Garcia D, Alexander JH, Wallentin L, Wojdyla DM, Thomas L, Hanna M, Al-Khatib SM, Dorian P, Ansell J, Commerford P, Flaker G, Lanas F, Vinereanu D, Xavier D, Hylek EM, Held C, Verheugt FW, Granger CB, Lopes RD (2014) Management and clinical outcomes in patients treated with apixaban vs warfarin undergoing procedures. Blood 124:3692–3698CrossRefGoogle Scholar
  14. 14.
    Tripodi A (2016) To measure or not to measure direct oral anticoagulants before surgery or invasive procedures. J Thromb Haemost 14:1325–1327CrossRefGoogle Scholar
  15. 15.
    Spyropoulos AC, Al-Badri A, Sherwood MW, Douketis JD (2016) To measure or not to measure direct oral anticoagulants before surgery or invasive procedures: comment. J Thromb Haemost 14:2556–2559CrossRefGoogle Scholar
  16. 16.
    Levy JH, Ageno W, Chan NC, Crowther M, Verhamme P, Weitz JI (2016) The subcommittee on control of anticoagulation. When and how to use antidotes for the reversal of direct oral anticoagulants: guidance from the SSC of the ISTH. J Thromb Haemost 14:623–627CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PharmacyUniversity of WashingtonSeattleUSA
  2. 2.Division of HematologyUniversity of WashingtonSeattleUSA
  3. 3.Department of Laboratory MedicineUniversity of WashingtonSeattleUSA

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