S4787 Unmasking Hemophilia: A Tale of Gastrointestinal Tract Bleeding and Diagnostic Challenges

Introduction: Acquired hemophilia A (AHA) is a rare autoimmune bleeding disorder caused by development of autoantibodies against factor VIII (FVIII). It typically presents with spontaneous bleeding, often in patients without prior bleeding history, posing diagnostic challenges. Gastrointestinal (GI) bleeding is an uncommon initial presentation of AHA, often leading to multiple invasive procedures before diagnosis. Early recognition is critical to prevent morbidity. Case Description/Methods: Case 1: A 53-year-old man with history of alcohol use disorder and chronic pancreatitis, presented with melena, generalized bruising, and significant weight loss. He had undergone prior endoscopies revealing duodenal ulceration without active bleeding. Laboratory evaluation showed normocytic anemia, thrombocytosis, elevated LDH, low haptoglobin, and prolonged aPTT that failed to correct on mixing studies. Despite concurrent lupus anticoagulant positivity, chromogenic FVIII activity assay confirmed severe FVIII deficiency, and Nijmegen-modified Bethesda assay identified high-titer FVIII inhibitors. He was successfully treated with corticosteroids, rituximab, and cyclophosphamide. Case 2: A 89-year-old woman with multiple comorbidities, presented with hematochezia following hemorrhoid banding and hemorrhoidectomy, requiring transfusion. Endoscopy revealed bleeding rectal ulcer controlled with hemostatic clips. Coagulation studies revealed prolonged aPTT uncorrected by mixing studies, low FVIII activity, and high inhibitor titers. She was managed with recombinant activated factor VII (rFVIIa), emicizumab, corticosteroids, rituximab, and cyclophosphamide, resulting in clinical stabilization and bleeding control. Discussion: These cases highlight the diagnostic complexity of AHA, particularly when presenting as GI bleeding. The presence of prolonged isolated aPTT should prompt evaluation for factor inhibitors, even in the setting of confounding lupus anticoagulant. Early diagnosis with specialized assays (chromogenic FVIII, Nijmegen Bethesda) is essential to avoid unnecessary procedures. Timely initiation of hemostatic agents such as rFVIIa and emicizumab, followed by immunosuppressive therapy, is critical for successful management and long-term remission.