An Overview of New Oral Anticoagulant Toxicity

Abstract

Extended life expectancy, changes in dietary habits, and a sedentary lifestyle have contributed to an increased risk of stroke and myocardial infarction. Atherosclerosis and thrombosis are the underlying causes of stroke and myocardial infarction. Anticoagulants have a significant role in both the prevention and treatment of these conditions. The difficulty of monitoring warfarin derivatives, which have been in use until recently, and their narrow therapeutic range paved the way for the development and use of new oral anticoagulants. Rivaroxaban, Apixaban, Edoxaban, and Betrixaban are Factor Xa inhibitors, while Dabigatran is a Thrombin (FIIa) inhibitor, and together they comprise the new oral anticoagulants. It is crucial to manage any accidental or intentional overdose with these new oral anticoagulants. The present review focuses on the characteristics of novel anticoagulants and their toxicological management.

Keywords

• thrombosis
• emergency
• anticoagulant
• stroke

References

1. Garcia D, Libby E, Crowther MA. The new oral anticoagulants. Blood, 2010;115(1), 15–20. https://doi. org/10.1182/blood-2009-09-241851
2. Atalan N. Hemostaz. GKD Anest Yoğ Bak Dern Derg, 2013;19(3), 109-112. https://doi.org/10.5222/ GKDAD.2013.109.
3. Acar BA, Akpınar ÇK, Alioğlu Z, Arlıer Z, Arsava EM, Aytaç E, et al. İnme klinik pratiğinde NOAK kullanımı: Türk Beyin Damar Hastalıkları Derneği Uzman Görüşü. Türk Beyin Damar Hastalıkları Dergisi 2020;26(3):190-235. https://doi. org/10.5505/tbdhd.2020.26213
4. Stangier J. Clinical pharmacokinetics and pharmacodynamics of the oral direct thrombin inhibitor dabigatran etexilate. Clinical pharmacokinetics, 2008;47(5), 285–295. https://doi. org/10.2165/00003088-200847050-00001
5. McBride L, Wang J, Ho P, Langsford D. Dabigatran Toxicity in Acute Kidney Injury: Hemodialysis and Idarucizumab Required. Kidney international reports, 2008;4(3), 500–504. https://doi.org/10.1016/j.ekir.2018.11.015 Pollack CV, Reilly PA, van Ryn J, Eikelboom JW, Glund S, Bernstein RA, et al. Idarucizumab for Dabigatran Reversal - Full Cohort Analysis. The New England journal of medicine, 2017;377(5), 431–441. https://doi.org/10.1056/ NEJMoa1707278
6. Miller KM, Brenner MJ. Betrixaban for Extended Venous Thromboembolism Prophylaxis in High-Risk Hospitalized Patients: Putting the APEX Results into Practice. Drugs, 2019;79(3), 291–302. https://doi.org/10.1007/ s40265-019-1059-y
7. Connolly SJ, Sharma M, Cohen AT, Demchuk AM, Członkowska A, Lindgren AG, et al. Andexanet for Factor Xa Inhibitor-Associated Acute Intracerebral Hemorrhage. The New England journal of medicine, 2024;390(19), 1745–1755. https://doi.org/10.1056/NEJMoa2313040
8. Milling TJ, Middeldorp S, Xu L, Koch B, Demchuk A, Eikelboom JW, et al. Final Study Report of Andexanet Alfa for Major Bleeding With Factor Xa Inhibitors. Circulation, 2023;147(13),1026–1038. https://doi. org/10.1161/CIRCULATIONAHA.121.057844

9. Dobesh PP, Fermann GJ, Christoph MJ, Koch B, Lesén E, Chen H, et al. Lower mortality with andexanet alfa vs 4-factor prothrombin complex concentrate for factor Xa inhibitor-related major bleeding in a U.S. hospital-based observational study. Research and practice in thrombosis and haemostasis, 2023;7(6), 102192. https://doi.org/10.1016/j. rpth.2023.102192
10. Neumann MA, Sieg N, Garcia Borrega J, Hüser C, Caspers M, Shimabukuro-Vornhagen A, et al. Überdosierung von direkten oralen Antikoagulanzien [Overdosing of direct oral anticoagulants]. Medizinische Klinik, Intensivmedizin und Notfallmedizin, 2024;10.1007/s00063-024-01154-8. Advance online publication. https://doi.org/10.1007/s00063-024-01154- 8
11. Boissier E, Senage T, Babuty A, Gouin-Thibault I, Rozec B, Roussel JC, et al. Heparin Anti-Xa Activity, a Readily Available Unique Test to Quantify Apixaban, Rivaroxaban, Fondaparinux, and Danaparoid Levels. Anesthesia and analgesia, 2021;132(3), 707–716. https://doi.org/10.1213/ ANE.0000000000005114
12. Bonanno FG. Management of Hemorrhagic Shock: Physiology Approach, Timing and Strategies. Journal of clinical medicine, 2022;12(1),260. https://doi.org/10.3390/ jcm12010260
13. Galvagno SM, Nahmias JT, Young DA. Advanced Trauma Life Support Update 2019: Management and Applications for Adults and Special Populations. Anesthesiology clinics, 2019;37(1),13–32. https://doi.org/10.1016/j. anclin.2018.09.009 Trauma and severe bleeding. Tranexamic acid within one hour to reduce mortality. Prescrire international, 2013;22(140), 189–190.