Emicizumab in Acquired Hemophilia A: Benefits in Bleed Control, Safety, and Cost-Effectiveness

Acquired hemophilia A (AHA) is a life-threatening autoimmune bleeding disorder in which autoantibodies neutralize factor VIII (FVIII) activity, precipitating severe bleeding with high morbidity and mortality.[1] Traditional management combines immunosuppressive therapy (IST) to eradicate the inhibitor with bypassing agents, such as factor VIII inhibitor bypassing activity (FEIBA) or recombinant activated factor VIIa, to control bleeding.[2] [3] However, especially in older patients with multiple comorbidities, aggressive IST can provoke opportunistic infections, neutropenia, and prolonged hospital admissions. Furthermore, the frequent intravenous dosing and short half-lives of bypassing agents increase health care costs and infection risk.[4] [5] Emicizumab, a bispecific monoclonal antibody that bridges FIXa and FX, mimics FVIII cofactor activity and offers subcutaneous prophylaxis with a favorable safety profile. Originally developed for congenital hemophilia A, its use in AHA is now under investigation.[6] [7]

An 82-year-old woman with rheumatoid arthritis, congestive heart failure, bronchiectasis, and osteoarthritis presented with fatigue, weight loss, and extensive spontaneous bruising. Laboratory evaluation revealed hemoglobin 78 g/L with reticulocytosis, a persistently prolonged activated partial thromboplastin time failing to correct on 1:1 mixing studies, FVIII <1 IU/dL, FIX 89.6 IU/dL, FXI 1.2 IU/dL, and von Willebrand factor activity 390.8 IU/dL. Imaging identified a large right-thigh hematoma and a pericardial hematoma in the context of previous pericardiectomy.

Initial hemostatic control required FEIBA with 3,500 to 5,000 units up to three times daily. Attempts to wean resulted in recurrent bleeding, necessitating 87 doses over 55 of the 60 days preceding emicizumab initiation. Bleeding occurred at cannula sites, thigh, and gluteal regions, necessitating multiple red cell transfusions. For inhibitor eradication, prednisolone 60 mg daily (1 mg/kg) and rituximab 375 mg/m² weekly for four doses were given, with mycophenolate mofetil 500 mg twice daily added on day 34. Severe neutropenia and septic complications ensued, mandating MMF cessation, broad spectrum antibiotics, and supportive care.

Given her intolerance to IST and FEIBA dependence, emicizumab was approved for off-label use by the Hospital's Medicines Management Committee on day 56. It was initiated after a 72-hour washout from FEIBA to minimize thrombotic microangiopathy risk. Emicizumab was commenced at 3 mg/kg weekly for 4 weeks, then 1.5 mg/kg weekly ([Fig. 1]). The patient remained bleeding-free during washout and maintained hemostatic control thereafter. Chromogenic FVIII assay using bovine reagents to measure the presence of native FVIII demonstrated endogenous FVIII rising by day 13 and peaking at 66.2 IU/dL on day 36. Prednisolone was tapered to 30 mg daily without further IST. She was taken off emicizumab and subsequently discharged after 75 days of hospitalization. Two months later, her FVIII declined to <1 IU/dL, prompting 11 further weekly maintenance doses with renewed hemostatic stabilization. At the last follow-up, 300 days postdiagnosis, endogenous FVIII was 66.5 IU/dL, 47 days after the final emicizumab dose.

Fig. 1 Serial FVIII activity and hemoglobin levels in relation to emicizumab initiation and adjunctive therapies (FEIBA, rituximab, mycophenolate mofetil). FEIBA, factor VIII inhibitor bypassing activity; FVIII, factor VIII.

Throughout her emicizumab therapy, the patient remained free from new bleeds and severe infections, aside from one episode of candidemia that resolved with antifungal agents. Repeated imaging demonstrated resolving pericardial and thigh hematomas. The use of bypassing agents was discontinued, and a safe discharge was planned without further recurrent bleeds and IST-related complications. In total, the number of bed days prior to emicizumab was 60 days compared with 15 days following initiation of emicizumab as bleed prophylaxis.

This case highlights the dual challenges of AHA management: Controlling severe bleeding while eradicating inhibitors. Conventional high-intensity IST and intermittent bypassing therapy carry substantial infection risk and hospital burden in older, comorbid patients.[4] [5] [8] [9] Emicizumab's rapid hemostatic control, favorable safety, subcutaneous administration, and prolonged half-life can reduce bypassing agent dependency and hospital stays, thereby lowering both clinical and economic burdens.[10] [11] [12] [13] Observational and phase II data demonstrate normalization of activated partial thromboplastin time, reduced or absent bleeds, minimal thromboembolic events, and swift achievement of remission.[7] [14] Comparative analyses indicate that prophylactic emicizumab alongside or ahead of IST decreases bleeding rates, fatal infections, and improves survival versus delayed IST without prophylaxis[15]; retrospective cohorts similarly show lower infection rates and comparable bleeding control.[15] [16] [17] Although thrombotic microangiopathy remains a concern, our patient experienced none despite prolonged FEIBA exposure and emicizumab washout.

Cost-effectiveness further underpins the value of emicizumab in AHA. Emicizumab can be given on an outpatient basis, thereby reducing hospital bed days and associated costs. Its acquisition cost compares favorably to the cumulative expense of FEIBA plus hospitalization. Although not a substitute for IST, it provides a cost-saving advantage by minimizing the need for frequent bypassing therapy. These findings mirror similar observations where emicizumab use in AHA was associated with reduced need for hospitalization, thereby providing cost-saving opportunities.[18]

Although this is a single case, it adds depth to the emerging narrative that emicizumab can offer advantages beyond pure bleed prevention. Further research will help optimize the use of emicizumab in different AHA phenotypes and establish cost-effectiveness in larger patient cohorts. With further studies and accumulating real-world evidence, emicizumab may become an increasingly attractive front-line therapy for bleed control in AHA.

In summary, emicizumab transformed bleed control in this elderly patient with severe AHA, delivering rapid and sustained hemostatic stability without adverse effects, reducing bypassing agent use and hospital bed days, and mitigating infection risk. These outcomes suggest that emicizumab may be both clinically beneficial and cost-effective in the management of AHA.

Ethical Approval

Ethics sought in the context of institutional consent to anonymized data use in service and outcome evaluations.

Patient Consent

Patient consent has been obtained and documented.

Authors' Contributions

G.G.: Data collection, data analysis, and writing—original draft. L.R.: Data collection, data analysis, and writing—original draft. M.S.: Writing—review and editing. E.D.: Writing—review and editing. C.H.: Writing—review and editing. J.T.: Conceptualization, writing—review and editing.

Publikationsverlauf

Eingereicht: 14. Juli 2025

Angenommen: 28. August 2025

Artikel online veröffentlicht:
09. September 2025

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