Andexanet alfa was approved in the US (2018) for patients treated with rivaroxaban and apixaban, when reversal of anticoagulation is needed due to life-threatening or uncontrolled bleeding. Prior to the approval of andexanet alfa, healthcare providers managed bleeding and reversal of anticoagulation with supportive measures and concentrated blood factors. In the pivotal ANNEXA-4 trial, no data for use in patients requiring urgent/emergent procedures were available, as patients were excluded if surgery was planned to occur within 12 hours. It was the goal of Dr. Sarah Culbreth and colleagues to investigate the use of andexanet alfa in patients taking Factor Xa inhibitors presenting with life-threatening major bleeding who subsequently required emergent procedures. As Culbreth stated, “Due to increased anti-Xa activity that was demonstrated in ANNEXA-A and -R volunteers two hours after the completion of infusion and the inability to rapidly measure Xa inhibitor levels at our institution, we considered infusion to incision time, duration of the procedure, and post-procedure bleeding risk when faced with bleeding patients who required surgical interventions.”
The team reviewed 26 cases involving the administration of andexanet alfa between May 2018 and May 2019, and found that nine patients required invasive procedures within 24 hours. Procedures included emergent neurosurgical procedures, a laminectomy, an exploratory laparotomy, and other invasive procedures. There were no thrombotic events observed within 7 days of reversal.
Culbreth and her colleagues concluded that based on their case review, “One in three patients requiring reversal with andexanet alfa for life threatening major bleeding underwent invasive procedures within 24 hours of andexanet alfa administration. Although adequate hemostasis was achieved in 89% of cases, the pharmacokinetic properties of andexanet alfa make it difficult to assess periprocedural bleeding risks. In order to optimize results in the absence of calibrated Xa inhibitor levels, careful evaluation of drug pharmacokinetics and pharmacodynamics is required, together with coordinated efforts between surgeons, pharmacists, and hematologists.”