Management of Factor Xa inhibitor-associated life-threatening major hemorrhage: A retrospective multi-center analysis

Abstract

Background Factor Xa (FXa) inhibitors, used for stroke prevention in atrial fibrillation and venous thromboembolism treatment and prevention, are the dominant non-Vitamin K oral anticoagulants on the market. While major bleeding may be less common with these agents compared to warfarin, it is always a risk, and little has been published on the most serious bleeding scenarios. This study describes a cohort of patients with FXa inhibitor-associated life-threatening bleeding events, their clinical characteristics, interventions and outcomes. Methods We performed a retrospective, 5-center review of FXa inhibitor-treated major bleeding patients. Investigators identified potential cases by cross-referencing ICD-9/10 codes for hemorrhage with medication lists. Investigators selected cases they deemed to require immediate reversal of coagulopathy, and reviewed charts for characteristics, reversal strategies and other interventions, and outcomes. Results A total of 56 charts met the inclusion criteria for the retrospective cohort, including 29 (52%) gastrointestinal bleeds (GIB), 19 (34%) intracranial hemorrhages (ICH) and 8 (14%) others. Twenty-four (43%) patients received various factor or plasma products, and the remainder received supportive care. Thirty-day mortality was 21% (n = 12). Re-anticoagulation within 30-days occurred in 23 (41%) patients. Thromboembolic events (TEEs) occurred in 6 (11%) patients. No differences were observed in outcomes by treatment strategy. Conclusions This cohort of FXa inhibitor-associated major bleeding scenarios deemed appropriate for acute anticoagulant reversal illustrates the variable approaches in the absence of a specific reversal agent.

Factor VIII Inhibitor Bypassing Activity (FEIBA) Reversal for Apixaban and Rivaroxaban in Patients With Acute Intracranial and Nonintracranial Hemorrhage

“…Clinically, FEIBA produces combined ICH and non-ICH effective hemostasis rates between 89% and 100% based on doses ranging between 25 and 50 U/kg. 22,23 In-hospital 23 or 30-day 22,24,25 post-FEIBA TEE ranges from 0% to at least as high as 8%.…”

Andexanet alfa in the treatment of acute major bleeding related to apixaban and rivaroxaban: a profile of its use in the USA

“…dabigatran) and factor Xa inhibitors (e.g. apixaban, rivaroxaban, edoxaban, and betrixaban), these newer anticoagulants are increasingly being used in lieu of warfarin [ 1 – 3 ]. Direct thrombin and factor Xa inhibitors provide anticoagulant efficacy similar to that of warfarin.…”

“…Direct thrombin and factor Xa inhibitors provide anticoagulant efficacy similar to that of warfarin. Moreover, these anticoagulants have many advantages over warfarin, including their wide therapeutic index, fixed dosing regimen without the need for frequent blood testing, rapid onset of action, and relatively low risk of drug interactions [ 1 – 3 ].…”

“…Although direct thrombin and factor Xa inhibitors show a better bleeding risk profile (e.g. a lower incidence of intracranial bleeding) than warfarin, all anticoagulants are associated with the risk of major hemorrhagic complications [ 3 – 6 ]. A rapid reversal of the anticoagulant effect is desirable as anticoagulant-associated hemorrhagic complications often lead to substantial use of healthcare resources [ 1 , 2 , 5 ].…”

“…Unlike warfarin and dabigatran, however, factor Xa inhibitor-associated major bleeding events have been managed with nonspecific reversal agents (e.g. PCC, FFP, and activated recombinant factor VIIa) due to lack of a specific reversal agent for factor Xa inhibitors [ 3 , 6 ]. The development of such a specific reversal agent may potentially promote the more widespread use of factor Xa inhibitors [ 6 ].…”