Acquired Von Willebrand Syndrome in a patient with Monoclonal Gammopathy of Unknown Significance: a case report

Abstract

AbstractBackground Monoclonal gammopathy of uncertain significance (MGUS) associated acquired von Willebrand syndrome (AvWS) is a rare life-threatening bleeding disorder driven by immunologic clearance of circulating von Willebrand factor (vWF). Treatments including factor replacement and intravenous immunoglobulin (IVIG) provide short-term bleeding control. Achieving a sustained response is frequently challenging and there remains lack of data regarding long-term management of MGUS-associated AvWS, specifically regarding plasma cell depleting agents. Case presentation: A 74-year-old female was diagnosed with AvWS while undergoing pre-operative workup for a knee replacement surgery. Peri-operative bleeding was successfully controlled with vWF/FVIII complex along with intravenous immunoglobulin (IVIG). However, she subsequently developed recurrent episodes of gastrointestinal bleeding without an identifiable source on upper endoscopy and colonoscopy. vWF/FVIII complex and IVIG only provided short-term bleeding control. Patient was then administered rituximab however, developed a severe infusion reaction and was not re-challenged. Incidentally, a circulating IgG kappa monoclonal paraprotein was noted, dating back to testing during initial diagnosis. Therefore, suspicion for MGUS-associated AvWS was raised and clonal directed treatment with bortezomib was initiated. Post 3 cycles of bortezomib, the monoclonal paraprotein became undetectable and there was normalization of vWF:Ag, vWF:RCo and factor VIII activity without recurrence of bleeding for over 18 months. Conclusions Clonal directed therapy with bortezomib resulted in eradication of the monoclonal paraprotein causing suppression of the underlying immunological process which led to a durable remission in our patient with MGUS-associated AvWS. Bortezomib may be considered as a viable treatment option to achieve long-lasting bleeding control in patients with MGUS-associated AvWS.