Andexanet alfa after 4-factor PCC administration for intracranial hemorrhage: a case series.

The ongoing controversy regarding optimal reversal agent for factor Xa-inhibitors is mainly due to lack of comparative data of andexanet alfa (AA) to 4-factor prothrombin complex concentrate (4F-PCC), institutional formulary restrictions, and navigation of clinical scenarios involving patients clinically worsen despite initial reversal efforts. The combination use of 4F-PCC and AA has not been evaluated in clinical trials and the outcomes of such patients with FXA-inhibitor associated intracranial hemorrhage (ICH) are unknown. A total of five patients, including four outside hospital transfers, received 4F-PCC prior to AA for FXa-inhibitor associated ICH (n = 3 apixaban, n = 2 rivaroxaban; n = 4 ICH, n = 1 TBI). The doses of 4F-PCC ranged from 25 to 60 units/kg and were administered within a range of 1.5-4.2 h prior to AA. One patient required surgical intervention with craniotomy and three patients underwent external ventricular drain placement. Two of the five patients developed an ischemic or thromboembolic complication within one week from 4F-PCC and AA administration. This case series discusses multiple unique patient cases in which 4F-PCC and AA were both administered for FXa-inhibitor associated ICH. The results highlight the potentially increased thrombotic risk associated with combination use. Ongoing post-marketing data collection of real patient case scenarios are essential to the establishment of consensus guidelines on how to prioritize initial reversal efforts and manage these patients during the course of their bleed.

Reversal of apixaban and rivaroxaban with andexanet alfa prior to invasive or surgical procedures.

BACKGROUND: Outcomes following andexanet alfa reversal of factor Xa inhibitors in patients requiring urgent or emergent invasive procedures are lacking. This study aimed to describe efficacy and safety outcomes following andexanet alfa administration within 24 h of an invasive procedure. METHODS: This single-center, observational, retrospective study included patients who received andexanet alfa within 24 h of an invasive or surgical procedure. The primary outcome was hemostatic efficacy graded as excellent, good, or poor using similar definitions to the ANNEXA-4 criteria. Secondary outcomes included hospital discharge disposition, intensive care unit (ICU) and hospital length of stay, 30-day mortality, 30-day thromboischemic event rates, and serum coagulation assay changes pre- and postreversal. RESULTS: Forty-four patients met inclusion criteria; of these, 27 (62.8%) received apixaban and 16 (37.2%) were treated with rivaroxaban prior to admission. The indications for reversal were categorized as intracranial (n = 20 [45.5%]) or extracranial (n = 24 [54.5%]) sites. Majority of patients required emergent operative procedures (18 [40.9%]), followed by invasive device placement (10 [22.7%]) or arterial embolization (9 [20.5%]). Thirty-eight (86.4%) patients were able to be adequately graded for hemostatic efficacy. Overall, 30 (78.9%) patients achieved excellent or good hemostasis within 24 h after periprocedural administration of andexanet alfa (19 [82.6%] apixaban vs. 11 [78.6%] rivaroxaban; 12 [80.0%] intracranial events vs. 18 [78.3%] extracranial events). Discharge disposition was most often to a short- or long-term care facilities (27 [61.4%]). Thirty-day mortality and thromboischemic complications occurred in 15 (34.1%) and 12 (27.3%) patients, respectively. Prothrombin time and antifactor Xa assay results were significantly decreased after andexanet alfa administration (p < 0.05) while thromboelastogram assay values (reaction time, kinetic time, and activated clotting time) showed nonsignificant changes pre- versus postreversal. CONCLUSION: Andexanet alfa may be used for urgent or emergent reversal of apixaban and rivaroxaban peri-procedurally with promising hemostatic outcomes. Further prospective, comparative clinical research is warranted.