S4681 Recurrent Gastrointestinal Bleeding in Type 2M Von Willebrand Disease: A Diagnostic and Therapeutic Challenge

Introduction: Von Willebrand Disease (VWD) is the most common inherited bleeding disorder, with type 2M representing a rare qualitative defect in von Willebrand Factor (VWF) that impairs platelet adhesion despite normal multimer distribution. Gastrointestinal (GI) bleeding is well-described in types 2A, 2B, and 3 due to loss of high-molecular-weight multimers, but less so in type 2M. Type 2M is often misclassified as type 1 or 2A, which can delay appropriate therapy. Management of VWD-related gastrointestinal bleeding is complex, often requiring endoscopic intervention, hormonal or antifibrinolytic agents, and VWF replacement. We present a rare case of recurrent, transfusion-dependent GI bleeding in type 2M VWD successfully managed with recombinant VWF (rVWF) prophylaxis. Case Description/Methods: We present a case of a 72-year-old woman diagnosed with type 2M VWD at age 48, with a history of menorrhagia, easy bruising, and past surgical procedures managed with DDAVP. At age 69, she developed recurrent melena and symptomatic anemia. Initial labs showed hemoglobin of 7.5 g/dL. Extensive GI evaluation, including EGD, colonoscopy, capsule endoscopy, computed tomography enterography, and device-assisted enteroscopy, failed to localize a bleeding source. Medical therapies—Desmopressin (DDAVP), tranexamic acid, and atorvastatin—were ineffective. Between ages 69 and 71, she required 13 PRBC transfusions, 19 iron infusions, multiple doses of DDVAP, and Humate P. Ultimately, she was started on weekly rVWF which resolved her GI bleeding, her hemoglobin stabilized, and she has remained completely transfusion-independent for over 12 months. The dosing interval was successfully extended to every 3 weeks with sustained improvement in symptoms and quality of life. Discussion: Recurrent GI bleeding in type 2M VWD is underreported and likely underrecognized due to diagnostic misclassification and lack of awareness. Angiodysplasia is a suspected mechanism, though frequently undetectable with standard imaging. This case illustrates the limited utility of DDAVP in type 2M and supports rVWF prophylaxis as a viable option when conventional therapies fail. Accurate VWD subtyping is essential for optimizing treatment. To our knowledge, this is the first reported case of successful long-term rVWF use in type 2M VWD with recurrent GI bleeding, resulting in complete transfusion independence.