Coagulation Factor Xa (Recombinant), Inactivated-Zhzo (Andexanet Alfa) Hemostatic Outcomes and Thrombotic Event Incidence at an Academic Medical Center

Abstract

Andexanet alfa is approved for the reversal of factor Xa inhibitors in patients with major bleeding events. We aimed to review the incidence of effective hemostasis with andexanet alfa in a real-world environment. This retrospective cohort included patients hospitalized for a major bleed that resulted in andexanet alfa administration. The primary outcome was effective hemostasis at 12 hours after andexanet alfa treatment. Thromboembolic events and mortality within 30 days were also assessed. Over a 14-month period, 13 patients received andexanet alfa with a mean age of 69 ± 10 years, 54% male, 69% exposed to apixaban (31% rivaroxaban), and had intracranial (46%) and nonintracranial (54%) bleeding sites. Effective hemostasis was observed in 10 (77%) patients. Four (31%) patients experienced 5 thromboembolic events with a median time to event of 6.5 days (range: 0.5-29). Four thrombotic events occurred during the period in which anticoagulation (prophylaxis or therapeutic) was not restarted. Mortality rate was 15%. Andexanet alfa was effective in obtaining hemostasis in a majority of patients. However, the incidence of thromboembolic events was high and may be attributed to a delay in restarting anticoagulation.

Evaluation of oral factor Xa inhibitor‐associated extracranial bleeding reversal with andexanet alfa

“…We report a 19% incidence of ischemic complications, which falls within the 0% to 31% range reported in previous andexanet alfa reversal studies 17,18,20‐22 . Importantly, andexanet alfa is not a procoagulant agent, but a decoy molecule that temporarily impairs anti‐FXa activity.…”

“…In our study we report a median 106 minutes between admission and antidote administration, and 64 minutes between antidote administration and surgical intervention on those patients who required it. Both the time to reversal and the time to surgery fall within the ranges of previous studies that reported it 17,18,22 . Considering the short half‐lives of FXa inhibitors, a delay in administering andexanet alfa will mean a slight reduction of anti‐FXa plasma levels, which also depends on the patient's ability to clear the drug.…”

“…We found andexanet alfa reversal for FXa inhibitor‐associated extracranial bleeding had a lower rate of hemostatic effectiveness compared with previous studies on DOAC‐associated bleeding. In prior studies evaluating reversal of FXa inhibitor‐associated bleeding with andexanet alfa, hemostatic effectiveness ranged from 57% to 91%, compared to 48% in our cohort 17,18,20‐22 . The relatively low rate of hemostatic effectiveness found in our study is potentially explained through differences in patient selection, as patients requiring surgical intervention were excluded in the ANNEXA‐4 trial 20 .…”

“…Clinician judgment of what constitutes life‐threatening bleeding forms the basis for patient selection at BWH and other centers that described their protocol, which more closely mirror the prescribing information published by the manufacturer (Figure 2). 17,21,22 All discussed protocols stated that indications not specified in the protocol may qualify for use of andexanet alfa after hematology or pharmacy consult and approval.…”

Institutional Experience of Using Andexanet Alfa

“…A single institutional experience of the use of andexanet alfa in 13 patients demonstrated effective hemostasis in 77% of the patients with a 31% incidence of thromboembolic events and a 15% mortality rate. There are few other single institutional case series on its use in a limited number of patients from large tertiary hospitals [ 20 - 21 ]. We hereby report the utilization of andexanet alfa in a rural community hospital through a retrospective review of patients at Guthrie Robert Packer Hospital who received andexanet from June 2019 to March 2020 for the reversal of life-threatening bleeding associated with rivaroxaban or apixaban.…”