Successful Control of Bleeding with Emicizumab in Aquired Haemophilia A: A Case Report

Background: Acquired hemophilia A (AHA) is a rare autoimmune disease caused by an inhibitory autoantibody against factor VIII (FVIII). AHA is associated with high mortality from underlying comorbidities and bleeding, but also from treatment complications. The therapeutic aim is twofold: control of bleeding and eradication of the inhibitor. Whereas recombinant F VIIa and FEIBA represent the mainstay for bleeding control, the immunosuppressive approach is less well defined.

Case Report: We report on a 21-year old woman with an unresolved multi-site autoimmune disorder who developed treatment-refractory AHA with severe bleeding complications.

At the age of 9, autoimmune haemolytic anemia and immune thrombocytopenia were diagnosed. Nine years later, the patient developed epidermolysis bullosa acquisita. Treatment protocols included prednisolone, ciclosporin A, immunoglobulin infusions, splenectomy and rituximab. She developed widespread verrucae as a potential side-effect of B cell depletion. In 2016, AHA was diagnosed when after the excision of verrucae unstoppable bleeding was noted. Her aPTT was 80 sec, FVIII activity < 0.25% and an inhibitor was diagnosed with 40 Bethesda units (BE). Initial bleeding was well controlled with rFVIIa. Immunosuppression was initiated with dexamethasone and cyclophosphamide and subsequently escalated with ofatumumab, bortezomib and daratumumab without any success. During this period, she required rFVIIa for intermediate to severe bleeding (in total 1693mg rFVIIa). Her coagulation status after 12 months was unchanged (aPTT 101 sec, F VIII activity < 0.25%, inhibitor 332 BE). Whole-genome sequencing did not identify any relevant immune defects. She underwent ITT with the modified Bonn-Malmö Protocol (11/2017) with immunoadsorption, immunoglobulin infusions, immunosuppression and high-dose FVIII substitution. After an initial remission (aPTT 33 sec, F VIII activity 130%, inhibitor < 0.5 BE), she relapsed immediately. Shortly after the relapse, the patient suffered progressively from bleeding complications especially in the upper and lower limbs (in total 958mg rFVIIa). The patient's health insurance accepted an off-label treatment plan with emicizumab in 5/2018, that was given according to the manufacturer's instructions and reached a concentration of 46-51 µg/ml quickly. Her F VIII activity (chromogenic) reached 6%, her inhibitor (chromogenic) remained at 350 BE. Since then, the patient did not have any further bleeding symptoms in everyday life, even following minor. In July 2018, the patient had a tooth extracted, without prior consultation of the haemostasis service. She subsequently experienced severe bleeds over seven days and required treatment with rFVIIa (131mg rFVIIa).

Conclusions: This is one of the first experiences with emicizumab in an AHA patient. It indicates that this drug may constitute a safe alternative to control bleeding in AHA.

No conflict of interest has been declared by the author(s).