Since their approval in 2010, direct oral anticoagulants (DOACs) have become integral in treating and preventing thromboembolic diseases. Their predictable pharmacokinetics, negating the need for frequent dose adjustments, offer considerable advantages.1 However, the management in patients with trauma on DOACs presents challenges, including the lack of standardized reversal protocols and the unclear clinical utility of concentration assessments in high-risk injuries.2 A study by Perkins et al of 245 patients with trauma investigates the implications of therapeutic, subtherapeutic or supratherapeutic DOAC levels as well as the associated clinical outcomes.3
The primary finding of this study is that there is wide variability in DOAC-specific anti-Xa levels among patients with trauma. Though this study was underpowered to detect an association between anti-Xa concentrations and transfusion, reversal or outcomes, one potentially notable finding is in the small subgroup of patients with intracranial hemorrhage (ICH). Progression of ICH was observed in 30% (3/10) of patients with supratherapeutic anti-Xa levels versus 9.8% (4/41) of patients with therapeutic or subtherapeutic levels. These data suggest that there may be a clinically significant risk to patients with supratherapeutic levels. Identification of patients with supratherapeutic levels and effective strategies for reversal, therefore, becomes a critical consideration and underscores the need for further research for DOAC management in trauma care.
Another notable finding is that female patients were more likely to demonstrate supratherapeutic levels (67% vs 33%) than male group. Anti-Xa concentrations among females also had a wide variation, demonstrated by a large IQR. Despite the theoretical understanding that DOACs have a more predictable therapeutic effect that negates the need for frequent monitoring, this difference in the predictability of levels between men and women raises questions about whether there is a biological difference in how individuals respond to DOACs.4 The seminal DOAC trials enrolled around 40% female patients; however, these studies were not examined for sex-specific outcomes.5 The absence of these data makes it difficult to generate conclusions about whether testing and reversal protocols should differ for men and women.6 7 Furthermore, the lack of standardized anti-Xa testing, with specifically calibrated levels required for each Xa inhibitor, complicates whether and how widely testing should be adopted. Nevertheless, Perkins et al highlight an interesting question of who would most benefit from anti-Xa testing and reversal.
As the use of DOACS will likely continue to be omnipresent, it will be imperative that trauma providers understand their clinical implications, the utility of anti-Xa testing and when reversal is indicated. Future research should focus on understanding the clinical impacts of reversal agents and conducting pragmatic analyses for their implementation in clinical practice, paving the way for more effective and personalized care for patients with trauma on DOAC therapy.
Footnotes
Contributors: All authors contributed to the content, literature review, drafting and editing of the manuscript.
Funding: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests: VPH spouse is a consultant to Zimmer Biomet, Sig Medical, Atricure, Astra Zeneca and has received research support from Medtronic.
Provenance and peer review: Commissioned; internally peer-reviewed.
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References
- 1. Ruff CT, Giugliano RP, Braunwald E, Hoffman EB, Deenadayalu N, Ezekowitz MD, Camm AJ, Weitz JI, Lewis BS, Parkhomenko A, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: a meta-analysis of randomised trials. Lancet 2014;383:955–62. 10.1016/S0140-6736(13)62343-0 [DOI] [PubMed] [Google Scholar]
- 2. Maegele M, Grottke O, Schöchl H, Sakowitz O, Spannagl M, Koscielny J. Direct oral anticoagulants in emergency trauma admissions: perioperative management, and handling hemorrhage. Dtsch Arztebl Int 2016;113:575. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Perkins L, Adams L, Lerner D, Santorelli J, Smith AM, Kobayashi L. Et alPredictors of direct oral anticoagulant concentrations in the trauma populationTrauma surgery. Trauma Surg Acute Care Open 2024;9:e001208. 10.1136/tsaco-2023-001208 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4. Samuelson BT, Cuker A. Measurement and reversal of the direct oral anticoagulants. Blood Rev 2017;31:77–84. 10.1016/j.blre.2016.08.006 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5. Ko D, Rahman F, Martins MAP, et al. Atrial fibrillation in women: treatment. Nat Rev Cardiol 2017;14:113–24. 10.1038/nrcardio.2016.171 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. Abou-Ismail MY, Citla Sridhar D, Nayak L. Estrogen and thrombosis: a bench to bedside review. Thromb Res 2020;192:40–51. 10.1016/j.thromres.2020.05.008 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. Siegerink B, Govers-Riemslag JWP, Rosendaal FR, Ten Cate H, Algra A. Intrinsic coagulation activation and the risk of arterial thrombosis in young women: results from the risk of arterial thrombosis in relation to oral contraceptives (RATIO) case-control study. Circulation 2010;122:1854–61. 10.1161/CIRCULATIONAHA.110.943738 [DOI] [PubMed] [Google Scholar]