The Management of Bleeding Induced by Oral Anticoagulant Therapy Requires Sharp Problem-Solving Skills 

What is the most effective way to control bleeding in patients treated with direct oral anticoagulants (DOACs)? Are reversal agents recommended in every case? These are some of the questions driving the lightning talk on Tuesday afternoon at Euroanaesthesia 2025, where experts will provide a refresher course in the management of life-threatening DOAC-associated bleeding episodes in the perioperative and emergency medicine settings.   

As the number of individuals treated with DOACs continues to increase across the globe¹, the tools for navigating DOAC-induced bleeding events have become part of the clinical arsenal in emergency departments and operating rooms. The reversal of DOACs is a key component in the acute management of patients who are experiencing life-threatening or major hemorrhage. International guidelines now recommend the use of reversal agents that target specific DOACs whenever possible. These include idarucizumab, which has obtained regulatory approval for the reversal of dabigatran, and andexanet alfa, which has been approved for reversing the effects of apixaban and rivaroxaban in patients experiencing life-threatening or uncontrolled bleeding events.  

While the evidence-based recommendations provide a framework for the management of DOAC-induced bleeding events, approaches may vary based on clinical scenarios and patient characteristics. “There is no [single] optimal approach,” according to Christian von Heymann, MD, a professor of anesthesiology and intensive care medicine at the Charité Medical School affiliated with the Humboldt University of Berlin, in Germany. “The effective and safe approach to [managing] patients who bleed under DOACs always has to consider surgery- and patient-specific factors.” Von Heymann, who co-authored the European guidelines on the reversal of DOACs in patients with life-threatening bleeding², will review findings from clinical trials that inform reversal strategies in case of DOAC-induced intracranial hemorrhage and other life-threatening bleeding episodes. 

“Reversal means neutralisation of the effect of a drug, in this case, an anticoagulant,” von Heymann said. “The neutralization is achieved by [the administration of] direct antidotes that inhibit the anticoagulant effect directly. Nonspecific hemostatic agents do not specifically inhibit anticoagulants but may improve the hemostatic function of the coagulation system.”  

The first step is to perform a comprehensive clinical evaluation—not only to localize the source of the bleeding and assess its severity, but also to evaluate the risk for thromboembolic events after reversal. “Clinicians have to [determine] whether the bleed is life-threatening and requires immediate action—either reversal or a non-hemostatic intervention—that outweighs [the risks of] possible thromboembolic events,” the speaker added.  

In the emergency department, where access to specific reversal agents is typically limited, clinicians must react quickly and use the resources at their disposal to identify and control DOAC-induced hemorrhage. “If specific reversal agents of DOACs are not available, the use of prothrombin complex concentrates is recommended, a practice supported by scientific evidence,” said Lidia Mora, MD, associate professor of anesthesiology at Universitat Autònoma Barcelona and a clinician in the department of anesthesiology at the Vall d’Hebron Trauma, Rehabilitation and Burns Hospital in Barcelona, Spain. “However, in the context of trauma, many studies are observational in nature, which limits the ability to offer definitive therapeutic recommendations.”  

The decision to reverse the effect of DOACs relies on information regarding the type of anticoagulant, the dosage, and the time of the last ingested dose. Advanced coagulation tests allow for a more comprehensive assessment of the coagulation process compared with routine coagulation tests and may help clinicians gain a more nuanced understanding of a patient’s hemostatic status. “In case of emergency reversal of a DOAC, the best option is to have access, in the shortest time possible, to the most accurate monitoring [method available],” Mora noted. “Since we are interested in the possible quantification of reversal and not just screening, conventional coagulation tests provide limited information. It is best to [perform] additional viscoelastic tests³, preferably with specific reagents for the detection of DOACs. My recommendation, for example, for a factor Xa inhibitor, include the urgent determination of its plasma level, a calibrated anti-Xa [assay] for the drug, and a viscoelastic test, preferably with a specific reagent. I would consider conventional coagulation tests [as a last resort], as they are unlikely to provide any useful information.”  

Mora stressed that the clinical team must always be aware of the risk of hemorrhage in patients on oral anticoagulant therapy and be ready to reverse the effect of DOACs within the optimal timeframe, to ensure the best outcomes in emergency scenarios. Integrating evidence-based recommendations into the clinical workflow and making the most of the available resources may eventually bridge the gap between the guidelines and clinical care.  

References: 

1. Pozzi A, Lucà F, Gelsomino S, et al. Coagulation Tests and Reversal Agents in Patients Treated with Oral Anticoagulants: The Challenging Scenarios of Life-Threatening Bleeding and Unplanned Invasive Procedures. J Clin Med. 2024;13(9):2451. 
2. Grottke O, Afshari A, Ahmed A, et al. Clinical guideline on reversal of direct oral anticoagulants in patients with life threatening bleeding. Eur J Anaesthesiol. 2024;41(5):327-350.   
3. Mora L, Pons-Pellicé L, Quintana-Díaz M. Viscoelastic monitoring of direct oral anticoagulants (DOAC). Blood Transfus. 2025 Jan;23(1):59-63.