Utilization of Emicizumab in Acquired Factor VIII Deficiency

Abstract

Objective:Rare disease Background:Acquired hemophilia A (AHA) is a rare autoimmune disease caused by immunoglobulins that bind and inactive factor VIII, thereby predisposing to life-threatening bleeding. Bleeding is typically stabilized by utilizing bypassing agents, such as recombinant factor VIIa (rVIIa). Select case reports have demonstrated the success of alternative prophylaxis for clearance of factor VIII inhibitors through the use of emicizumab, a current FDA approved medication for treatment of congenital hemophilia A. In this case report we present the efficacy of utilizing emicizumab as a prophylactic agent in a patient that was unable to tolerate first-line therapy for prophylaxis. Case Report:A 91-year-old male presented for ongoing hematuria for 5 weeks with prior workup unrevealing. He was given a day's course of recombinant factor VIIa to stabilize his bleeding and was started on cyclophosphamide and prednisone after a revealing hematological workup including activated partial thromboplastin time (aPTT) >100 seconds and factor VIII inhibitor level of 44 BU/mL. He continued to require VIIa infusions to control his bleeding and was started on emicizumab once stabilized. His bleeding remained controlled and his inhibitor decreased after 6 months of therapy with repeat factor VIII inhibitor level of 1.9 BU/mL. Conclusions:The success of utilizing emicizumab for bleeding prophylaxis in AHA is demonstrated by this patient's resolution of bleeding. The high frequency of dosing and higher risk for thrombosis with factor VIIa, in conjunction with our patient's medical history and ease of administration, make emicizumab an ideal agent for bleeding prophylaxis while awaiting clearance of factor VIII inhibitors.

Should emicizumab be used in patients with acquired hemophilia A?

“…Since emicizumab was launched in the European union in 2018, four single-case reports [36][37][38][39] and one retrospective series of patients 40 have been published (Table 2). At least one clinical trial is currently planned and estimated to be completed in 2022 (NCT04188639).…”

Persistent inhibitor in acquired haemophilia A: A case for emicizumab?

“…A once-weekly subcutaneous administration facilitates treatment greatly to a previously unknown extent. 5 Sufficient haemostatic efficacy has been reported in a recent series of 12 patients 6 and in several single cases with persisting autoantibodies after refractory immunosuppressive therapy and/or failure of standard bypassing agents [7][8][9] including complex cases such as reported by Dane et al with AHA and coronary artery disease and repeated indication for PCI. 7 We report a patient with a severe form of acquired haemophilia showing a prolonged refractory course of disease with persisting autoantibodies and failure of conventional therapeutic strategies for whom hospital discharge could be made possible by the switch to off-label treatment with emicizumab.…”

Off‐label use of emicizumab in persons with acquired haemophilia A and von Willebrand disease: A scoping review of the literature

“…Of the 33 patients, 26 (78.8%) received haemostatic therapy prior to emicizumab initiation. [15][16][17][18][19][22][23][24][25][26] Haemostatic therapy was not required in five (15.2%) patients 23,26 and not reported in two (6%) patients. 20,21 rFVIIa was the most commonly used haemostatic agent (20/26, 76.9%), [16][17][18][19][23][24][25][26] followed by aPCC (7/26, 26.9%) 15,18,22,23,25 and rp-FVIII (7/26, 26.9%).…”