CO-78 | REAL-WORLD MANAGEMENT OF ACQUIRED HEMOPHILIA A: FOCUS ON RECOMBINANT PORCINE FVIII AS FIRST-LINE HEMOSTATIC TREATMENT AND LONG-TERM OUTCOMES

Abstract

Background. Acquired Hemophilia A (AHFA) is a rare bleeding disorder caused by the development of neutralizing autoantibodies against endogenous coagulation factor VIII (FVIII). The clinical presentation is often characterized by sudden, severe subcutaneous and mucosal hemorrhages. Management is inherently complex: it requires the immediate restoration of hemostasis and the simultaneous eradication of the inhibitor via immunosuppressive therapy (IST). Given that AHA predominantly affects the elderly population, treatment must be carefully tailored to account for multiple comorbidities and a high baseline thrombotic risk. This study provides a deep dive into the efficacy of rpFVIII as a first-line agent and analyzes the long-term clinical outcomes and challenges in a real-world setting.Methods. We conducted a retrospective observational study of 11 consecutive patients (7 males, 4 females) with AHA. The median age at diagnosis was 78 years (24–88). At presentation, the median residual FVIII level was 2.0%, while the median inhibitor titer was 13.5 Bethesda Units (BU), though the cohort included a significant outlier at 269 BU. The clinical complexity was high: 7 patients (64%) presented a significant baseline thrombotic risk, 5 (45%) had a history of or active malignancy, and 3 were receiving oral anticoagulant therapy (2 on Coumadin, 1 on DOAC) for underlying atrial fibrillation or TEV. Additionally, two cases were identified following recent COVID-19 infection, one of which was a fourth reinfection, suggesting a potential immunological trigger.Results. Active hemostatic treatment was required for 8 patients (73%). rpFVIII was utilized as the primary first-line hemostatic agent at an initial dosage of 100 mg/kg. The median number of administrations required to achieve stable hemostasis was 5.5 (mean: 5.25; range: 1–8). Two patients required a switch to second-line therapy with rFVIIa due to the development of anti-porcine FVIII antibodies (ADA), with titers reaching 30 and 45 BU. One patient was successfully transitioned to Emicizumab prophylaxis (starting 24 days post-diagnosis). The median time to inhibitor eradication was 21 days (mean: 25.9 days; range: 6–56). Relapse occurred in only one patient (the outlier patient) following self-discontinuation of steroid therapy. Post-eradication, two deaths occurred due to unrelated causes (urological sepsis and stroke), and two patients were lost to follow-up.Conclusions. rpFVIII proved to be an effective first-line hemostatic agent, particularly in elderly patients with complex comorbidities. However, the development of anti-ADA antibodies remains a critical factor that may necessitate a therapeutic switch. Our data confirm that a standardized IST approach achieves inhibitor eradication in a median of three weeks, though high-titer patients require strict monitoring and adherence to prevent relapses.