Recommendations for the use of andexanet alfa in the management of bleeding in patients on oral factor Xa inhibitors in Switzerland

Abstract

Anticoagulants are essential in preventing and treating thrombosis. Unfortunately, their use is accompanied by an enhanced risk of bleeding. Since the introduction of direct oral anticoagulants (DOACs), the risk of major bleeding has been reduced but not eliminated. Major bleeding events related to the use of factor Xa inhibitors can be challenging to manage. In recent years, four-factor prothrombin complex concentrates have been used in patients with severe bleeding taking oral direct factor Xa inhibitors (apixaban, edoxaban and rivaroxaban). Andexanet alfa (OndexxyaTM, AstraZeneca AG) is a specially designed recombinant version of human factor Xa that acts as a decoy receptor to reverse the effects of factor Xa inhibitors. Since 2 December 2020, andexanet alfa has been used in Switzerland for adult patients receiving apixaban or rivaroxaban when reversal of anticoagulation is required because of life-threatening or uncontrolled bleeding. However, the use of andexanet alfa remains a challenge owing to its cost, the reported thrombotic complications and the fact that its efficacy mainly relates to intracranial haemorrhage. Moreover, the use of nonspecific reversal agents together with andexanet alfa is controversial. The present recommendations on the use of andexanet alfa in the management of bleeding in patients on factor Xa inhibitors in Switzerland were developed by a group of Swiss experts from the Working Party Hemostasis of the Swiss Society of Hematology. These recommendations aim to provide support to clinicians in their decision-making in the management of patients with major bleeding receiving factor Xa inhibitors.

Use of Andexanet Alfa for Factor Xa Inhibitor Reversal in US Verified Trauma Centers: A National Survey

“…Multiple professional organizations (American College of Cardiology, American College of Chest Physicians, American College of Emergency Physicians, American College of Gastroenterologists-Canadian College of Gastroenterologists, European Stroke Working Group, Anticoagulation Forum, European Heart Rhythm Association, Swiss Society of Hematology) have recommended Andexxa as a first line agent in the reversal of direct oral factor Xa inhibitors as it relates to major hemorrhage. 12 , 13 , 18 – 23 Despite these recommendations, many levels 1 and 2 trauma centers use PCC for reversal of these drug agents. Our study results supported this; the survey was sent to trauma surgeons associated with levels 1 and 2 trauma centers, with the majority reporting utilization of 4F-PCCs as the personal preference and institutional preference for trauma patients on apixaban and rivaroxaban needing anticoagulation reversal due to life-threatening bleeding.…”

“…However, our study findings suggest andexanet alfa is not as readily available at trauma centers despite current recommendations from professional medical organizations in favor of its use as a first-line agent. 12 , 13 , 19 , 21 – 23 , 25 …”

Coagulation Tests and Reversal Agents in Patients Treated with Oral Anticoagulants: The Challenging Scenarios of Life-Threatening Bleeding and Unplanned Invasive Procedures

“…Although specific studies to assess the management of anticoagulated patients with ICH are unavailable, the Swiss Society of Hematology has recently provided some recommendations [44,46,47]. Specifically, in the presence of ICH, andexanet alfa has been suggested in those patients without severe neurological impairment (Glasgow Coma Scale >7), with symptom onset occurring in less than sixh, life expectancy >1 month, and last intake of apixaban/rivaroxaban <15 h or anti-Xa >100 ng/mL.…”

“…Specifically, in the presence of ICH, andexanet alfa has been suggested in those patients without severe neurological impairment (Glasgow Coma Scale >7), with symptom onset occurring in less than sixh, life expectancy >1 month, and last intake of apixaban/rivaroxaban <15 h or anti-Xa >100 ng/mL. Since there is a lack of data available from the ANNEXA-4 trial regarding patients treated with edoxaban [15], the Swiss Society of Hematology does not consider the use of andexanet alfa but rather four-factor PCC in patients treated with these Xa inhibitors [47]. However, a recent study assessed the efficacy of andexanet alfa in significantly reducing factor Xa activity in 36 patients treated with edoxaban [48].…”