Should emicizumab be used in patients with acquired hemophilia A?

Abstract

Emicizumab is currently approved to prevent bleeding in patients with congenital hemophilia A with or without neutralizing antibodies (inhibitors) against factor VIII (FVIII). Here, we present a case‐based discussion of its potential use in acquired hemophilia A (AHA), a severe bleeding disorder caused by autoantibodies against FVIII. State‐of‐the‐art management is based on bypassing agents (recombinant factor VIIa, activated prothrombin complex concentrate) and recombinant porcine FVIII; immunosuppressive therapy (corticosteroids, rituximab, cyclophosphamide) is used to suppress autoantibody formation. Case reports and one series suggest that emicizumab can reduce the risk of bleeding and the requirement for hemostatic therapy until remission of AHA is achieved. Further, it may allow to postpone the start of immunosuppressive therapy or to use less intense regimens. However, the risk‐benefit assessment of emicizumab in AHA is difficult because demographic and clinical characteristics are different compared with congenital hemophilia. Prospective clinical trials are needed before the use of emicizumab can be recommended in AHA.

Emicizumab in acquired haemophilia A: about two clinical cases and literature review

“…This explains the need for aggressive immunosuppressive therapy. 17 , 18 Based on the available data and our own experience, emicizumab’s major advantages include its ease of use, rapid haemostatic prophylactic efficacy and reduced requirement of aggressive immunosuppressant agents. This last advantage should not be overlooked, as infectious complications related to immunosuppression are the primary death cause in AHA patients.…”

“… 1 , 3 , 13 , 14 Finally, in our experience and as reported in the literature, transfusion requirements have decreased rapidly from the first emicizumab dose onwards, thereby reducing the risk of ischaemic anaemia-related complications, as well as that of repeated transfusions, including alloimmunization, volume overload, pulmonary oedema and iron overload. 18 …”

Emicizumab reduces re‐hospitalization for bleeding in acquired haemophilia A

“…The emicizumab use reported in this population to date 3,4 has been immediately following diagnosis and used in conjunction with bypassing agents (BPA) for the treatment of the presenting haemorrhagic event. 4,5 Reported benefits in upfront emicizumab use included earlier discharge and the ability to use less immunosuppression with less adverse effects. Emicizumab reportedly resulted in haemostasis and discontinuation of BPAs after 1.5 (1-4) days with the concurrent use of immunosuppression (steroids and/or rituximab), and no recurrent bleeding was observed.…”

“…Four such patients were hospitalized for acute bleeding in 2020. All were treated with recombinant porcine VIII (rpFVIII) as previously reported, 5 or with recombinant activated factor VII (rFVIIa) if they had developed antiporcine FVIII (anti-pFVIII) antibodies. Emicizumab (3 mg/kg subcutaneous weekly for 4 doses, followed by 1.5 mg/kg weekly) was initiated after resolution of bleeding and prior to discharge.…”

New Developments in Diagnosis and Management of Acquired Hemophilia and Acquired von Willebrand Syndrome

“…Bypassing agents could be stopped after 1.5 days. Several other cases using other dose regimens of emicizumab in AHA have been reported and are reviewed by Tiede et al 27 It was concluded that emicizumab may be able to shorten the duration of initial bleeds and recurrent bleeding, but more data from prospective clinical trials is needed.…”