Targeting early immunologic decline in acquired hemophilia A: A case for prophylactic rituximab

Abstract Acquired hemophilia A (AHA) is a rare autoimmune bleeding disorder caused by autoantibodies against factor VIII (FVIII). While immunosuppressive therapy is often effective in inducing remission, relapse occurs in up to 30% of patients. At present, current guidelines focus on the management of active bleeding or confirmed inhibitor recurrence but do not offer guidance on the role of prophylactic immunosuppression in patients at risk of relapse. We present the case of an 81-year-old man with idiopathic AHA and a mechanical aortic valve on chronic coumadin. He was initially diagnosed in 2019 during a hospitalization for persistent hematuria following spinal surgery. Laboratory workup revealed an isolated prolonged aPTT with FVIII activity <1% and high-titer inhibitors. His initial course was marked by severe bleeding, requiring 17 units of packed red blood cells and 140,000 units of recombinant FVIII. Following treatment with triple immunosuppressive therapy including prednisone, rituximab, and cyclophosphamide, he achieved remission. Remission was sustained for nearly three years, until 2022, when he developed a clinical relapse with recurrent hematuria and an iliopsoas hematoma. He again required significant transfusion support, recombinant FVIII, and emicizumab to control bleeding, followed by a second course of rituximab and cyclophosphamide. Both episodes involved significant clinical bleeding and, despite the presence of a mechanical valve, required prolonged interruptions of anticoagulation, placing him at considerable thromboembolic risk. Following treatment, he achieved a second durable remission, with FVIII activity >200% over the next two years. In December 2024, however, routine surveillance revealed a stepwise decline in FVIII activity—200%, 178%, 147%, 96%, and 78%—in the absence of clinical symptoms. This consistent downward trend raised concern for early immune reactivation. Given his prior clinical relapse, history of severe bleeding, and recurrent interruptions in anticoagulation, a prophylactic immunosuppressive approach was pursued by his medical team. To reduce the risk of relapse and allow for uninterrupted anticoagulation, prophylactic rituximab was administered at 100 mg weekly for four weeks. Following the first dose, FVIII activity increased to 125% and later exceeded 200% by the third week. Throughout this period, he remained asymptomatic, with no bleeding, adverse events, or interruptions to anticoagulation. Furthermore, continued surveillance confirmed sustained biochemical remission. This case introduces a novel prophylactic role for rituximab in AHA, guided by biochemical surveillance rather than clinical relapse. This strategy draws parallels to early rituximab use in thrombotic thrombocytopenic purpura and suggests that biomarker-directed prophylaxis could be feasible in AHA. Initiating immunosuppression in response to a downward trend in FVIII activity—prior to inhibitor detection or bleeding— may help sustain remission and prevent relapse in high-risk patients, while potentially reducing morbidity and mortality. Beyond its clinical impact, this approach may also offer significant cost savings by reducing the need for costly agents such as recombinant FVIII (obizur) or emicizumab. Further investigation is warranted to define relapse thresholds, evaluate safety, and determine the broader applicability of prophylactic immunosuppression in AHA patients.