Four-factor prothrombin complex concentrate plus andexanet alfa for reversal of factor Xa inhibitor–associated bleeding: Case series

Abstract

Disclaimer In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose To manage factor Xa (FXa) inhibitor–associated bleeding, andexanet alfa or 4-factor prothrombin concentrate (4F-PCC) has been used to restore hemostasis. However, literature on the outcomes for patients who received both andexanet alfa and 4F-PCC is limited. Summary We report a case series of 5 patients who received andexanet alfa plus 4F-PCC for reversal of FXa inhibitor–associated bleeding. Patients were included in this case series if they received both andexanet alfa and 4F-PCC for reversal of FXa inhibitor–associated bleeding. They were followed to either discharge or death, and in-hospital complications related to concurrent use of andexanet alfa and 4F-PCC were documented. We report an incidence of thromboembolism of 40% (2 of 5 cases) and an in-hospital mortality rate of 60% (3 of 5 cases). Taking these cases together with those in the existing literature, we found a total of 23 reported cases of safety outcomes with andexanet alfa plus 4F-PCC. The overall incidence of thromboembolism was 35% (8 of 23 cases). Conclusion This case series adds to the limited literature describing the outcomes for patients receiving andexanet alfa plus 4F-PCC. We encourage other institutions to report safety data on administering both agents.

Co-administration of Four-Factor Prothrombin Complex Concentrate With Andexanet alfa for Reversal of Nontraumatic Intracranial Hemorrhage

“…12,16 Liu et al reported a thrombosis incidence similar to this analysis (40%) and also combined previous data to find an incidence of in-hospital thromboembolism of 35% based on eight of 23 cases. 28 This study's data combined with that of Liu et al and Bradshaw et al shows a thromboembolism incidence of 15 cases in 37 total cases, or 40.54%. Unfortunately, the data in other case reports were not easily distinguished by neurologic bleed compared to bleeds of other locations, so this incidence of thromboembolism is an approximation and rates in only ICH patients cannot be fully estimated without further study.…”

“…In fact, the most recent of such case series by Liu et al pooled thromboembolism incidence from previous studies and found that the combination of 4F-PCC and andexanet alfa led to an incidence of thromboembolism of 35%. 28 Another recent case series by Bradshaw et al found that 2 of 5 patients (40%) experienced thromboembolism. 29 This analysis examines patients who received both 4F-PCC and andexanet alfa for reversal of factor Xa inhibitor-associated nontraumatic intracranial bleeding at a large academic medical center, with the goal of defining safety and efficacy outcomes.…”

“…In fact, the most recent of such case series by Liu et al pooled thromboembolism incidence from previous studies and found that the combination of 4F-PCC and andexanet alfa led to an incidence of thromboembolism of 35%. 28 Another recent case series by Bradshaw et al found that 2 of 5 patients (40%) experienced thromboembolism. 29 …”

Antidote vs. unspecific hemostatic agents for the management of direct oral anticoagulant-related bleeding in trauma

“…Within 3 days, two of the five patients developed an ischemic or thromboembolic complication and two intrahospital deaths occurred. Liu et al [89] reported a 40% thromboembolism rate and an in-hospital mortality of 60% in five patients who received 4F-PCC and andexanet concomitantly. They further investigated the available literature identifying 23 cases of concomitant therapy of which 8 patients developed thromboembolic complications (35%).…”

The use of andexanet alpha in the Polish setting: An interdisciplinary protocol. Expert consensus statement of the Polish Cardiac Society

“…Given the lack of clinical data on the safety of the combined use of AA and prothrombin complex concentrate (PCC), activated prothrombin complex concentrate (aPCC), recombinant factor VIIa, fresh frozen plasma (FFP) or whole blood, such use should be avoided unless absolutely necessary. Several case series have been published on this topic, with the results highlighting the potentially increased thrombotic risk associated with the use of the AA and PCC combination [18,19].…”