Recommendations of Polish Cardiac Society expert regarding the use of andexanet alpha in the Polish context. An interdisciplinary protocol.

Andexanet alfa (AA) is a recombinant, inactive analog of human factor Xa (FXa), effectively reversing the effects of its inhibitors - rivaroxaban and apixaban, which are available in Poland. The drug was granted registration after the publication of the ANNEXA-4 trial (Andexanet Alfa, a Novel Antidote to the Anticoagulation Effects of FXA Inhibitors 4), in which its efficacy in restoring hemostasis in life-threatening hemorrhages in a group of patients using the aforementioned anticoagulants was proven. Hence, AA is now recommended for patients receiving apixaban or rivaroxaban therapy with massive and uncontrollable hemorrhages, including hemorrhagic strokes (HS) and gastrointestinal bleeding. Drug-specific chromogenic anti-Xa assays are generally best suited for estimating rivaroxaban and apixaban plasma levels, aside from direct assessment of their concentrations. The absence of anti-Xa activity, determined using these assays, allows to outrule the presence of clinically relevant plasma concentrations of the FXa inhibitor. On the other hand, the dose of AA should not be modified based on the results of hemostasis tests, as it depends solely on the time elapsed since the last dose of FXa inhibitor, and on the dose and type of long-term medication used. AA is administered as an intravenous (i.v.) bolus, followed by an i.v.infusion of the drug. The maximum reversal of anti-Xa activity occurs within two minutes of the end of the bolus treatment, with the continuation of the continuous i.v. infusion allowing the effect to be maintained for up to two hours afterwards. Because anticoagulant activity can reappear after the infusion is completed, it is currently unclear at what point after AA administration FXa inhibitors or heparin should be readministered.