Intravenous Immunoglobulin Induces Sustained Hemostatic Responses in IgM Paraprotein-Associated Acquired Von Willebrand Syndrome.

Acquired von Willebrand syndrome (AVWS) associated with monoclonal gammopathy is rare, and current evidence suggests that intravenous immunoglobulin (IVIG) is effective primarily in IgG-mediated disease, with limited benefit in IgM-associated cases. We describe a patient with life-threatening AVWS associated with IgM lambda monoclonal gammopathy secondary to lymphoplasmacytic lymphoma who demonstrated a sustained response to IVIG. A previously healthy woman developed severe mucocutaneous and gastrointestinal bleeding followed by intracranial hemorrhage despite treatment with desmopressin, von Willebrand factor (VWF) concentrates, and antifibrinolytic therapy. Diagnostic evaluation revealed reduced VWF antigen, VWF activity, and factor VIII levels, along with an IgM lambda paraprotein and biopsy-confirmed lymphoplasmacytic lymphoma with MYD88 mutation. During hospitalization for intracranial hemorrhage, she received VWF replacement and a single dose of IVIG (1 g/kg). VWF antigen increased from baseline values in the 20% range to 93% within 24 hours, peaked at 318% by day 4, and remained elevated at 117% 17 days later, far exceeding the expected duration of replacement therapy alone. This case challenges the prevailing assumption that IVIG lacks efficacy in IgM-associated AVWS and suggests that some patients may derive meaningful clinical benefit, particularly when urgent hemostatic control is required.