Andexanet alfa in the treatment of acute major bleeding related to apixaban and rivaroxaban: a profile of its use in the USA

Abstract

Andexanet alfa (Andexxa®), a first-in-class recombinant modified factor Xa protein, is currently the only specific agent available to reverse life-threatening or uncontrolled bleeding with the factor Xa inhibitors apixaban and rivaroxaban. Andexanet alfa acts as a decoy and competes with endogenous factor Xa to bind factor Xa inhibitors, thereby reversing the anticoagulant effects of factor Xa inhibitors, and restoring the activity of endogenous factor Xa. In adults with major bleeding associated with the use of apixaban or rivaroxaban, intravenous administration of andexanet alfa effectively and rapidly reduces anti-factor Xa levels, with reduced levels being maintained during continued treatment. The tolerability profile of andexanet alfa in patients is generally similar to that reported of other approved anticoagulation reversal agents. With the known increased risk of thromboembolic events following andexanet alfa treatment, anticoagulant therapy should be resumed as soon as medically appropriate.

Thrombin Generation Profile in Various Lymphoma Sub-Groups and Its Augmentation by Andexanet Alfa

“…32 Andexanet alfa act as a decoy protein which lacks enzymatic activity, in this recombinant protein the serine active site is replaced by alanine and the gamma-carboxyglutamic acid (GLA) domain is removed to restrict its assemblage into prothrombinase complex. 34 Since the availability of andexanet alfa, its use has been reported to be associated with thrombotic complications. A full study report on andexanet alfa associated bleeding with FXa inhibitors, reported that 49 patients (14%) out of 352 patients died within 30 days.…”

“… 30 – 33 While andexanet alfa is designed to act as a decoy to factor Xa inhibitors, it has multiple interactions with endogenous plasma proteins such as tissue factor pathway inhibitor (TFPI). 34 , 35 Moreover, because of this structural similarity to factor Xa, it may augment the effects of other serine proteases in the coagulation cascade presumably, by competing with the active sites of this enzyme. Lymphoma patients represent heterogenous group where the activation of hemostatic processes is multifactorial.…”

Proximale osteosynthetisch versorgte Femurfrakturen: Der Versorgungszeitpunkt verzögert sich bei vorbestehender Antikoagulation

“…Die Halbwertszeit ist mit 1 h sehr kurz [25]. In einer noch laufenden Phase-IIIb/IV-Studie ("ANNEXA-Studie") zeigten Zwischenergebnisse die signifikante Senkung der Anti-Faktor-Xa-Aktivität bei Patienten mit lebensbedrohlichen Blutungen [11][12][13]. In der vorliegenden Auswertung fielen unter "Sonstige" Patienten mit Einnahme von z.…”

Institutional Experience of Using Andexanet Alfa

“…In May 2018, andexanet was approved by the FDA for use in life-threatening bleeding in patients treated with apixaban or rivaroxaban [ 15 ]. It is used when the last dose of factor Xa inhibitor is <8 hours/unknown (if apixaban <5 mg/rivaroxaban <10 mg) or >8 hours irrespective of the dose [ 16 ]. There is a black-box warning for arterial and venous thromboembolic events, ischemic events, cardiac arrests, and sudden deaths [ 17 ].…”