Skip to main content

Advertisement

SpringerLink
Log in

DOAC plasma concentration upon hospital admission in a cohort of trauma patients. An observational real-life study

  • Original Article
  • Published:
European Journal of Trauma and Emergency Surgery Aims and scope Submit manuscript

Abstract

Purpose

Due to a better safety profile, direct oral anticoagulants (DOACs) are increasingly prescribed for prevention of thromboembolic events. However, little is known about DOAC plasma concentrations in trauma patients upon hospital admission. Thus, we investigated the frequency and extent of DOAC possible over- and underdosing in trauma patients upon hospital admission.

Methods

In this single-center retrospective study, DOAC plasma concentrations of adult trauma patients were analyzed with specific calibrated anti-IIa (dabigatran) and anti-Xa (apixaban, edoxaban and rivaroxaban) tests within 4 h after hospital admission.

Results

A total of 210 trauma patients, admitted between 2019 and 2022, were included in the analyses. Low DOAC levels < 30 ng/mL were detected in 13.3% of the patients. In 7.1% of the patients, DOAC plasma levels ranged between 300–399 ng/mL and further 7.1% exhibited plasma concentrations > 400 ng/mL. The highest incidence of high to very high DOAC plasma concentration was observed for patients on rivaroxaban and dabigatran. A moderate correlation was observed between dabigatran plasma concentration and estimated glomerular filtration rate (rho = − 0.5338, p = 0.0003). For rivaroxaban no clear association between plasma concentration and liver or renal function could be detected. Patients on statins had significantly higher DOAC concentration in comparison with those not taking statins (153 (76–274) vs 108 (51–217) ng/mL, p = 0.046).

Conclusion

The current study revealed that patients on dabigatran and rivaroxaban were prone to higher DOAC plasma levels upon hospital admission in comparison with apixaban and edoxaban. DOAC plasma level measurement in trauma patients might be warranted due to unpredictively low or high plasma concentrations. However, the clinical impact of altered plasma levels on both, bleeding and thromboembolic events, remains to be determined by future studies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data availability

The dataset analyzed in the current study are available from the corresponding author on reasonable request.

References

  1. van der Hulle T, Kooiman J, den Exter PL, Dekkers OM, Klok FA, Huisman MV. Effectiveness and safety of novel oral anticoagulants as compared with vitamin K antagonists in the treatment of acute symptomatic venous thromboembolism: a systematic review and meta-analysis. J Thromb Haemost. 2014;12:320–8.

    Article  PubMed  Google Scholar 

  2. Douxfils J, Gosselin RC. Laboratory assessment of direct oral anticoagulants. Semin Thromb Hemost. 2017;43:277–90.

    Article  CAS  PubMed  Google Scholar 

  3. Bruckbauer M, Prexl O, Voelckel W, Ziegler B, Grottke O, Maegele M, Schöchl H. Impact of direct oral anticoagulants in patients with hip fractures. J Orthop Trauma. 2019;33:e8–13.

    Article  PubMed  Google Scholar 

  4. Connolly SJ, Crowther M, Eikelboom JW, Gibson CM, Curnutte JT, Lawrence JH, Yue P, Bronson MD, Lu G, Conley PB, Verhamme P, Schmidt J, Middeldorp S, Cohen AT, Beyer-Westendorf J, Albaladejo P, Lopez-Sendon J, Demchuk AM, Pallin DJ, Concha M, Goodman S, Leeds J, Souza S, Siegal DM, Zotova E, Meeks B, Ahmad S, Nakamya J, Milling TJ Jr. Full study report of andexanet alfa for bleeding associated with factor Xa inhibitors. N Engl J Med. 2019;380:1326–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Pollack CV Jr, Reilly PA, van Ryn J, Eikelboom JW, Glund S, Bernstein RA, Dubiel R, Huisman MV, Hylek EM, Kam CW, Kamphuisen PW, Kreuzer J, Levy JH, Royle G, Sellke FW, Stangier J, Steiner T, Verhamme P, Wang B, Young L, Weitz JI. Idarucizumab for dabigatran reversal—full cohort analysis. N Engl J Med. 2017;377:431–41.

    Article  CAS  PubMed  Google Scholar 

  6. Oberladstätter D, Voelckel W, Bruckbauer M, Zipperle J, Grottke O, Ziegler B, Schöchl H. Idarucizumab in major trauma patients: a single centre real life experience. Eur J Trauma Emerg Surg. 2021;47:589–95.

    Article  PubMed  Google Scholar 

  7. January CT, Wann LS, Calkins H, Chen LY, Cigarroa JE, Cleveland JC Jr, Ellinor PT, Ezekowitz MD, Field ME, Furie KL, Heidenreich PA, Murray KT, Shea JB, Tracy CM, Yancy CW. 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(2019):e125–51.

    PubMed  Google Scholar 

  8. Steffel J, Verhamme P, Potpara TS, Albaladejo P, Antz M, Desteghe L, Haeusler KG, Oldgren J, Reinecke H, Roldan-Schilling V, Rowell N, Sinnaeve P, Collins R, Camm AJ, Heidbüchel H. European Heart rhythm association practical guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation. Eur Heart J. 2018;39(2018):1330–93.

    Article  CAS  PubMed  Google Scholar 

  9. Chen A, Stecker E. Direct oral anticoagulant use: a practical guide to common clinical challenges. J Am Heart Assoc. 2020;9: e017559.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Hofer H, Oberladstätter D, Schlimp CJ, Voelckel W, Zipperle J, Lockie C, Grottke O, Osuchowski M, Schöchl H. Role of DOAC plasma concentration on perioperative blood loss and transfusion requirements in patients with hip fractures. Eur J Trauma Emerg Surg. 2022;2:2.

    Google Scholar 

  11. Douxfils J, Adcock DM, Bates SM, Favaloro EJ, Gouin-Thibault I, Guillermo C, Kawai Y, Lindhoff-Last E, Kitchen S, Gosselin RC. Update of the international council for standardization in haematology recommendations for laboratory measurement of direct oral anticoagulants. Thromb Haemost. 2021;121(2021):1008–20.

    PubMed  Google Scholar 

  12. Seiffge DJ, Kägi G, Michel P, Fischer U, Béjot Y, Wegener S, Zedde M, Turc G, Cordonnier C, Sandor PS, Rodier G, Zini A, Cappellari M, Schädelin S, Polymeris AA, Werring D, Thilemann S, Maestrini I, Berge E, Traenka C, Vehoff J, De Marchis GM, Kapauer M, Peters N, Sirimarco G, Bonati LH, Arnold M, Lyrer PA, De Maistre E, Luft A, Tsakiris DA, Engelter ST. Rivaroxaban plasma levels in acute ischemic stroke and intracerebral hemorrhage. Ann Neurol. 2018;83:451–9.

    Article  CAS  PubMed  Google Scholar 

  13. Spahn DR, Bouillon B, Cerny V, Duranteau J, Filipescu D, Hunt BJ, Komadina R, Maegele M, Nardi G, Riddez L, Samama CM, Vincent JL, Rossaint R. The European guideline on management of major bleeding and coagulopathy following trauma. Crit Care. 2019;23:98.

    Article  PubMed  PubMed Central  Google Scholar 

  14. van den Dries CJ, van Doorn S, Souverein P, Pajouheshnia R, Moons KGM, Hoes AW, Geersing GJ, van den Ham HA. The number of concomitant drugs and the safety of direct oral anticoagulants in routine care patients with atrial fibrillation. TH Open. 2020;4:e417–26.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Reyes JL, Herzog CA, Yan H, Roetker NS, Wetmore JB. Prescribing patterns of direct-acting oral anticoagulants in patients with atrial fibrillation and chronic kidney disease: a retrospective cohort analysis. J Cardiovasc Pharmacol Ther. 2022;27:10742484221142220.

    Article  CAS  PubMed  Google Scholar 

  16. Oberladstätter D, Voelckel W, Schlimp C, Zipperle J, Ziegler B, Grottke O, Schöchl H. A prospective observational study of the rapid detection of clinically-relevant plasma direct oral anticoagulant levels following acute traumatic injury. Anaesthesia. 2021;76:373–80.

    Article  PubMed  Google Scholar 

  17. Ferri N, Colombo E, Tenconi M, Baldessin L, Corsini A. Drug-drug interactions of direct oral anticoagulants (DOACs): from pharmacological to clinical practice. Pharmaceutics. 2022;14:2.

    Article  Google Scholar 

  18. Chan YH, Chao TF, Lee HF, Yeh YH, Chang SH, Kuo CT, Lip GYH, Chen SA. Different renal function equations and dosing of direct oral anticoagulants in atrial fibrillation. JACC Asia. 2022;2:46–58.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Rizos T, Meid AD, Huppertz A, Dumschat C, Purrucker J, Foerster KI, Burhenne J, Czock D, Jenetzky E, Ringleb PA, Haefeli WE. Low exposure to direct oral anticoagulants is associated with ischemic stroke and its severity. J Stroke. 2022;24:88–97.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Wiegele M, Schöchl H, Haushofer A, Ortler M, Leitgeb J, Kwasny O, Beer R, Ay C, Schaden E. Diagnostic and therapeutic approach in adult patients with traumatic brain injury receiving oral anticoagulant therapy: an Austrian interdisciplinary consensus statement. Crit Care. 2019;23:62.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Prabhakaran K, Gogna S, Lombardo G, Latifi R. Venous thromboembolism in geriatric trauma patients-risk factors and associated outcomes. J Surg Res. 2020;254:327–33.

    Article  PubMed  Google Scholar 

  22. Testa S, Paoletti O, Legnani C, Dellanoce C, Antonucci E, Cosmi B, Pengo V, Poli D, Morandini R, Testa R, Tripodi A, Palareti G. Low drug levels and thrombotic complications in high-risk atrial fibrillation patients treated with direct oral anticoagulants. J Thromb Haemost. 2018;16:842–8.

    Article  CAS  PubMed  Google Scholar 

  23. Levy JH, Ageno W, Chan NC, Crowther M, Verhamme P, Weitz JI. When and how to use antidotes for the reversal of direct oral anticoagulants: guidance from the SSC of the ISTH. J Thromb Haemost. 2016;14:623–7.

    Article  CAS  PubMed  Google Scholar 

  24. Reilly PA, Lehr T, Haertter S, Connolly SJ, Yusuf S, Eikelboom JW, Ezekowitz MD, Nehmiz G, Wang S, Wallentin L. The effect of dabigatran plasma concentrations and patient characteristics on the frequency of ischemic stroke and major bleeding in atrial fibrillation patients: the RE-LY Trial (Randomized Evaluation of Long-Term Anticoagulation Therapy). J Am Coll Cardiol. 2014;63:321–8.

    Article  CAS  PubMed  Google Scholar 

  25. Sennesael AL, Larock AS, Douxfils J, Elens L, Stillemans G, Wiesen M, Taubert M, Dogné JM, Spinewine A, Mullier F. Rivaroxaban plasma levels in patients admitted for bleeding events: insights from a prospective study. Thromb J. 2018;16:28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Gulilat M, Tang A, Gryn SE, Leong-Sit P, Skanes AC, Alfonsi JE, Dresser GK, Henderson SL, Rose RV, Lizotte DJ, Teft WA, Schwarz UI, Tirona RG, Kim RB. Interpatient variation in rivaroxaban and apixaban plasma concentrations in routine care. Can J Cardiol. 2017;33:1036–43.

    Article  PubMed  Google Scholar 

  27. Mamas MA, Batson S, Pollock KG, Grundy S, Matthew A, Chapman C, Manuel JA, Farooqui U, Mitchell SA. Meta-analysis comparing apixaban versus rivaroxaban for management of patients with nonvalvular atrial fibrillation. Am J Cardiol. 2022;166:58–64.

    Article  CAS  PubMed  Google Scholar 

  28. Ageno W, Beyer-Westendorf J, Rubboli A. Once- versus twice-daily direct oral anticoagulants in non-valvular atrial fibrillation. Expert Opin Pharmacother. 2017;18:1325–32.

    Article  CAS  PubMed  Google Scholar 

  29. Raschi E, Bianchin M, Gatti M, Squizzato A, De Ponti F. Comparative effectiveness and safety of direct oral anticoagulants: overview of systematic reviews. Drug Saf. 2019;42:1409–22.

    Article  PubMed  Google Scholar 

  30. Giugliano RP, Ruff CT, Braunwald E, Murphy SA, Wiviott SD, Halperin JL, Waldo AL, Ezekowitz MD, Weitz JI, Špinar J, Ruzyllo W, Ruda M, Koretsune Y, Betcher J, Shi M, Grip LT, Patel SP, Patel I, Hanyok JJ, Mercuri M, Antman EM. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2013;369:2093–104.

    Article  CAS  PubMed  Google Scholar 

  31. Hohmann C, Lutz M, Vignali S, Borchert K, Seidel K, Braun S, Baldus S, Näbauer M. Clinical outcomes in patients receiving edoxaban or phenprocoumon for prevention of stroke in atrial fibrillation: a German real-world cohort study. Thromb J. 2022;20:37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Gong IY, Kim RB. Importance of pharmacokinetic profile and variability as determinants of dose and response to dabigatran, rivaroxaban, and apixaban. Can J Cardiol. 2013;29:S24-33.

    Article  PubMed  Google Scholar 

  33. Milner E, Ainsworth M, Gleaton M, Bookstaver D. Assessment of anti-Xa activity in patients receiving concomitant apixaban with strong p-glycoprotein inhibitors and statins. J Clin Pharm Ther. 2022;47:668–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We want to thank Dr. Christopher Lockie for his kind support in proofreading this article.

Author information

Authors and Affiliations

  1. Department of Anaesthesiology and Intensive Care Medicine, AUVA Trauma Centre Salzburg, Academic Teaching Hospital of the Paracelsus Medical University, Dr. Franz Rehrl Platz 5, 5020, Salzburg, Austria

    Carolin Ruoff, Herbert Schöchl, Gerhard Fritsch, Wolfgang Voelckel & Daniel Oberladstätter

  2. Paracelsus Medical University, Salzburg, Austria

    Carolin Ruoff

  3. Ludwig Boltzmann Institute for Traumatology, The Research Centre in Cooperation With AUVA, Vienna, Austria

    Herbert Schöchl, Gerhard Fritsch, Johannes Zipperle & Daniel Oberladstätter

  4. Department of Anaesthesiology, Intensive Care Medicine and Pain Medicine, Medical University of Vienna, Vienna, Austria

    Johannes Gratz

  5. Department of Anaesthesiology, Heidelberg University Hospital, Heidelberg, Germany

    Felix Schmitt

Authors
  1. Carolin Ruoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Herbert Schöchl
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gerhard Fritsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wolfgang Voelckel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Johannes Zipperle
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Johannes Gratz
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Felix Schmitt
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Daniel Oberladstätter
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Herbert Schöchl.

Ethics declarations

Conflict of interest

H.S. has received honoraria for participation in advisory board meetings for Bayer Healthcare, Boehringer Ingelheim, Alexion and Octapharm. He has also received speaker fees from Haemonetics and Vifor, and study grants from CSL Behring. J.G. has received honoraria, research funding, and travel reimbursement from Alexion, Boehringer Ingelheim, CSL Behring, Johnson & Johnson, Instrumentation Laboratory, Mitsubishi Tanabe Pharma, Novo Nordisk, Octapharma, and Portola. No other external funding or competing interests declared.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ruoff, C., Schöchl, H., Fritsch, G. et al. DOAC plasma concentration upon hospital admission in a cohort of trauma patients. An observational real-life study. Eur J Trauma Emerg Surg 49, 2543–2551 (2023). https://doi.org/10.1007/s00068-023-02334-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00068-023-02334-5

Keywords

Search

Navigation