CC BY 4.0 · TH Open 2021; 05(04): e570-e576
DOI: 10.1055/a-1692-1415
Original Article

Measurement of Anticoagulation in Patients on Dabigatran, Rivaroxaban, and Apixaban Therapy by Novel Automated Thrombelastography

1   Essentia Health St. Mary's Heart and Vascular Center, Duluth, Minnesota, United States
2   Bispebjerg University of Copenhagen Hospital, Department of Cardiology, Copenhagen, Denmark
,
Joao D. Dias
3   Haemonetics Corp., Braintree, Massachusetts, United States
,
Mark Walsh
4   Memorial Hospital of South Bend, Department of Energy Medicine, Sound Bend, Indiana, United States
,
Kevin Bliden
5   Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, Baltimore, Maryland, United States
,
Jorn D. Nielsen
2   Bispebjerg University of Copenhagen Hospital, Department of Cardiology, Copenhagen, Denmark
,
Maren Anderson
6   University of Minnesota School of Medicine, Duluth, Minnesota, United States
,
Brian C. Thurston
7   Spartanburg Regional Medical Center, Division of Surgery, Spartanburg, South Carolina, United States
,
Udaya S. Tantry
5   Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, Baltimore, Maryland, United States
,
Jan Hartmann
3   Haemonetics Corp., Braintree, Massachusetts, United States
,
5   Sinai Center for Thrombosis Research and Drug Development, Sinai Hospital of Baltimore, Baltimore, Maryland, United States
› Author Affiliations
Funding This study was funded by the Haemonetics Corporation.

Abstract

Background Direct-acting oral anticoagulants (DOACs) do not require monitoring. Measurement of DOAC effect would be useful in the event of bleeding, trauma, and thromboembolism while on anticoagulation. We evaluated the effectiveness of the investigational DOAC assays on the TEG®6s Hemostasis Analyzer to assess the anticoagulant effect of DOACs in patients treated for atrial fibrillation or deep vein thrombosis (DVT).

Methods Patients on treatment for a minimum of 7 days with standard doses of dabigatran, rivaroxaban, and apixaban were included. DOAC plasma concentrations and TEG®6s Reaction (R)-time were measured and correlated. The sensitivity, specificity, and negative predictive value (NPV) of R-time to detect DOAC concentrations of ≥30, ≥50, and ≥100 ng/mL were calculated.

Results A total of 189 patients were included, (n = 50) on apixaban, (n = 62) on rivaroxaban, (n = 53) on dabigatran, and (n = 24) on no DOAC were studied. Using the direct thrombin inhibitor (DTI) channel, R-time demonstrated strong linear correlation with dabigatran levels (r = 0.93, p < 0.0001). Using the antifactor Xa (AFXa) channel, R-time demonstrated strong nonlinear correlation with rivaroxaban and apixaban levels (r s = 0.92 and 0.84, respectively, p < 0.0001 for both). R-time revealed strong sensitivity and NPV in detecting low DOAC levels for the predefined concentrations.

Conclusion R-time measured by TEG®6s DOAC-specific cartridge has a strong correlation with concentrations of the most commonly used DOACs with high sensitivity and NPV for detecting lower drug levels that are considered clinically relevant for patients in need of antidote, or prior to urgent surgery. Further studies to determine the relation of R-time to clinical outcomes are warranted.

Authors' Contributions

R.A. and J.H. conceived and designed the study. M.W., K.B., B.C.T., M.A., J.D.N., and P.A.G. contributed to data collection and interpretation. All authors revised the article for important intellectual content and approved the final version for submission.


Conflict of Interests

J.D.D. and J.H. were employees of Haemonetics Corporation at the time of the study. This study was supported by Haemonetics Corporation (Boston, Massachusetts, United States). The other authors have no other relevant financial interest in the products or companies described in this article.




Publication History

Received: 25 March 2021

Accepted: 04 November 2021

Accepted Manuscript online:
09 November 2021

Article published online:
30 December 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Douxfils J, Ageno W, Samama CM. et al. Laboratory testing in patients treated with direct oral anticoagulants: a practical guide for clinicians. J Thromb Haemost 2018; 16 (02) 209-219
  • 2 Gurbel PA, Bliden KP, Tantry US. et al. First report of the point-of-care TEG: a technical validation study of the TEG-6S system. Platelets 2016; 27 (07) 642-649
  • 3 Bliden KP, Chaudhary R, Mohammed N. et al. Determination of non-vitamin K oral anticoagulant (NOAC) effects using a new-generation thrombelastography TEG 6s system. J Thromb Thrombolysis 2017; 43 (04) 437-445
  • 4 Artang R, Anderson M, Nielsen JD. Fully automated thromboelastograph TEG 6s to measure anticoagulant effects of direct oral anticoagulants in healthy male volunteers. Res Pract Thromb Haemost 2019; 3 (03) 391-396
  • 5 Dias JD, Lopez-Espina CG, Ippolito J. et al. Rapid point-of-care detection and classification of direct-acting oral anticoagulants with the TEG 6s: implications for trauma and acute care surgery. J Trauma Acute Care Surg 2019; 87 (02) 364-370
  • 6 Godier A, Dincq AS, Martin AC. et al. Predictors of pre-procedural concentrations of direct oral anticoagulants: a prospective multicentre study. Eur Heart J 2017; 38 (31) 2431-2439
  • 7 Levy JH, Ageno W, Chan NC, Crowther M, Verhamme P, Weitz JI. 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 2016; 14 (03) 623-627
  • 8 Seiffge DJ, Kägi G, Michel P. et al; Novel Oral Anticoagulants in Stroke Patients study group. Rivaroxaban plasma levels in acute ischemic stroke and intracerebral hemorrhage. Ann Neurol 2018; 83 (03) 451-459
  • 9 Gosselin RC, Adcock DM, Bates SM. et al. International Council for Standardization in Haematology (ICSH) recommendations for laboratory measurement of direct oral anticoagulants. Thromb Haemost 2018; 118 (03) 437-450
  • 10 Deeks JJ, Altman DG. Diagnostic tests 4: likelihood ratios. BMJ 2004; 329 (7458): 168-169
  • 11 January CT, Wann LS, Calkins H. et al. 2019 AHA/ACC/HRS focused update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society in Collaboration With the Society of Thoracic Surgeons. Circulation 2019; 140 (02) e125-e151
  • 12 Hindricks G, Potpara T, Dagres N. et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association of Cardio-Thoracic Surgery (EACTS). Eur Heart J 2020; 29: ehaa612
  • 13 Testa S, Paoletti O, Legnani C. et al. Low drug levels and thrombotic complications in high-risk atrial fibrillation patients treated with direct oral anticoagulants. J Thromb Haemost 2018; 16 (05) 842-848
  • 14 Eikelboom JW, Quinlan DJ, Hirsh J, Connolly SJ, Weitz JI. Laboratory monitoring of non-vitamin K antagonist oral anticoagulant use in patients with atrial fibrillation: a review. JAMA Cardiol 2017; 2 (05) 566-574
  • 15 Artang R, Anderson M, Riley P, Nielsen JD. Assessment of the effect of direct oral anticoagulants dabigatran, rivaroxaban, and apixaban in healthy male volunteers using a thrombin generation assay. Res Pract Thromb Haemost 2017; 1 (02) 194-201