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Presentation Details
| Treatment of Acquired Von Willebrand's Syndrome in the Setting of Monoclonal Dysproteinemias Fatima Shaba, Serena Navitskas, Erin Aakre, Amanda Hertel, Dong Chen, Rajiv Pruthi, Meera Sridharan. Mayo Clinic, Rochester, MN, USA |
Abstract
Abstract Background Acquired Von Willebrand’s syndrome is understood to occur via three main mechanisms: Increased clearance of Von Willebrand's factor (VWF), increased adsorption of VWF multimers, and interference of von Willebrand's multimers. In some AVWS related to dysproteinemias, there is a characteristic of interference seen in von Willebrand's factor multimers. We sought to better understand the clinical features of individuals who have dysproteinemias that affect VWF multimers; and how their Von Willebrand’s factor levels responded to treatment. Methods Twenty individuals with elevated monoclonal proteins and abnormal von Willebrand’s factor multimers seen on gel electrophoresis were identified through search of the Mayo Clinic’s Coagulation Laboratory database. Afterwards, these individuals were further analyzed through chart review and characterized by bleeding episodes, diagnosis, and treatment effects. Results VWF studies were obtained due to: epistaxis (n=3), retinal hemorrhage (n=1), hyper viscosity (n=1), post procedural bleeding (n=1), anemia (n=2), hemorrhagic stroke (n=2), spinal hematoma resulting in cauda equina syndrome (n=1), and other bleeding episodes (n=4). 3 had Multiple Myeloma (2 with IgM predominance, 1 with IgA predominance), 1 had IgG MGUS, 3 had IgM MGUS, and 13 with Waldenström's macroglobulinemia. 17 individuals were treated. Of these individuals, 2 individuals had IgM MGUS and received treatment with rituximab due to one having spontaneous bleeding episodes and another having an unexplained hemorrhagic stroke. Treatment included: Bendamustine/rituximab (n=9), Bendamustine alone (n=1), Rituximab (n=2), Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone (n=3), ibrutinib (n=1), and Bortezomib (n=1) Table 1. The median IgM was 5910 mg/dL, and the max IgM level seen was 9290 mg/dL. In the individual with IgA gammopathy, their IgA was 6000 mg/dL, and median IgG was 1750 mg/dL in the individual with IgG gammopathy. The median VWF antigen level for all individuals prior to treatment was 31.5% (minimum of 15%, max 136%), VWF activity level was 29% (min 9, max 128), and Factor VIII level was 39% (min 15%, max 140%). After treatment, median VWF antigen level was 101% (min 33%, max 260%), VWF activity level 87.5% (min 30%, max 179%), and Factor VIII 117% (min 42%, max 192%). P values were calculated between groups based on treatment including: VWF antigen levels (p=0.0019584), VWF activity levels (p=0.008), Factor VIII levels (p=0.00208), and IgM mg/dL levels (p=0.0058) Table 2. Conclusion In individuals with elevated monoclonal proteins and acquired von Willebrand syndrome, treatment of the underlying monoclonal protein is associated with improving von Willebrand factor levels. There was a statistically significant difference in Von Willebrand’s factor antigen (p=0.0019), activity levels (p=0.008), and factor VIII (0.00208) for individuals with monoclonal dysproteinemias after treatment. IgM levels were lowered after treatment of monoclonal dysproteinemias in individuals with IgM gammopathy (p=0.0058). Having abnormally low VWF and subsequently acquired von Willebrand’s syndrome is not a benign condition as it can lead to serious bleeding outcomes as seen in 3 individuals in this study. Treating the dysprotein also improves acquired Von Willebrand's disorder.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.