Acquired hemophilia a results from a provincial registry highlight the need for improvement of clinical outcomes and bypassing agent use

Abstract Background Acquired Hemophilia A (AHA) is a rare disease with substantial morbidity and mortality. High quality evidence to guide and individualize management are limited. Treatment focuses on controlling bleeding and immunosuppression of the underlying inhibitor, usually requiring hospital admissions. We recently established a provincial AHA registry in British Columbia (BC), Canada. The objective of the present study was to describe AHA presentation, treatment, healthcare utilization/costs, and clinical outcomes from within the BC AHA Registry, prior to availability of emicizumab for AHA in BC. Methods Consecutive cases of AHA in BC between 2018 and 2024 were identified by screening all Bethesda assays run at the centralized special coagulation lab at St. Paul's Hospital in Vancouver, Canada, and were included in the registry. Patients with congenital Hemophilia A were excluded. with inhibitors Data from included cases were abstracted from the medical record into a REDCap database, including presenting AHA features, laboratory characteristics, treatments, health system utilization/cost, and clinical outcomes, the latter of which were captured continuously until the sooner of death, December 31, 2024, or loss to follow-up. Bleed severity was determined as per the International Society of Thrombosis and Hemostasis assessment guidelines. Data were analyzed using descriptive statistics. Results: The AHA registry includes 40 cases from 2018 through 2024, inclusive. Median age was 75 years (range 41-92) and 62.5% were male. At diagnosis the mean inhibitor titer was 109 Bethesda units (BU) with half of patients presenting with inhibitor titer > 20 BU. Eleven patients (27.5%) had both >20BU and FVIII < 1% at presentation. Ten patients had a history of solid organ malignancy at the time of diagnosis and one patient was postpartum. At diagnosis 93% of patients reported bleeding symptoms and according to ISTH guidelines was severe in 63%. Cutaneous or subcutaneous bruising was the most common manifestation, occurring in 60%, followed by mucosal bleeding in 23%, gastrointestinal bleeding in 20%, and genitourinary bleeding in 20%. Bleeding at multiple sites was the presenting feature in 45% of patients. Immunosuppressive therapy (IST) varied. In total, 37 patients (93%) received some form of IST, with all cases initiated on steroids at diagnosis, 25 also receiving cyclophosphamide, and 12 receiving rituximab at a median of 5 weeks after starting IST (range 1–36). Within 1 year, 23% had documented infectious complications of IST. Complete bypassing agent usage data were available for 32 of 40 patients. FEIBA was used in 53% of cases (median 44947 IU, range 0 – 278358 IU), recombinant factor VIIa in 70% (median 228 mg, range: 0 – 1522 mg), and recombinant porcine FVIII in 24% (median 10275 IU, range 0– 96486 IU). None received emicizumab prophylaxis. Most patients had multiple products used. During initial hospitalization, median total cost per patient of bypassing agents was CAD $249,000 (range: $16,000 – $2,100,000). The median initial hospital length of stay (LOS) was 23 days (range 8 – 65). Three patients required ICU stay during the initial diagnosis. Relapse occurred in 6 patients at a median time of 4 months after diagnosis. Mortality within 2 years of diagnosis was 20% (8 patients) of which five deaths were AHA related, including 3 deaths due to bleeding and 2 due to complications of immunosuppression. Conclusion Our registry findings, prior to availability of emicizumab for AHA in BC, demonstrates considerable morbidity and mortality in AHA associated with both the disease and its treatments, including long LOS and high cost associated with use of bypassing agents. This data serves as a benchmark of system costs and outcomes for the evaluation of ongoing changes in AHA care, including the use of emicizumab prophylaxis for significant bleeding and upfront rituximab in initial management of AHA, to decrease the burden of hospital and bypassing agent exposure.

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