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Presentation Details
| Visualization and Characterization of von Willebrand Multimer Banding Patterns in Acquired von Willebrand Syndrome:A Retrospective Study Serena D.Navitskas1, Fatima Shaba2, Rajiv K.Pruthi1, 2, Dong Chen1, Meera Sridharan1, 2. 1Department of Laboratory Medicine, Rochester, MN, USA.2Department of Medicine, Rochester, MN, USA |
Abstract
Background
Patients with plasma cell dyscrasias may develop acquired von Willebrand syndrome (AVWS), often associated with monoclonal proteins. Mechanisms include antibody-mediated clearance or inhibition of von Willebrand factor (VWF), and, less commonly, non-specific paraprotein/VWF complex formation. In addition to reduced VWF antigen and activity or decreased antigen/activity ratio, the VWF multimer pattern may be distorted. Objectives
This study characterizes laboratory abnormalities in AVWS patients with distorted multimer patterns, illustrating the spectrum of electrophoretic abnormalities (Figure 1). Multimer patterns are further classified by paraprotein type/strength, other causes, and treatment effects (Figure 2). Methods
The Mayo Clinic Coagulation Laboratory information system was searched (2014–2025) for individuals at Mayo Clinic (MN, FL, AZ) with distorted VWF multimer banding; external samples were excluded. Patient charts were reviewed for monoclonal gammopathies, AVWS, and treatment effects. The lab-developed VWF multimer assay demonstrates clear banding of the full VWF multimer range. Results were descriptively analyzed versus controls and known VWD patterns. When repeated, patterns persisted or intensified with x2 dilution (4.7% SDS) if VWF antigen/activity <30%. Similar patterns have been described on a smaller scale. Results
Among 4,040 internal patients evaluated, twenty-two showed significant interference on multimer gels. Of these, twenty had elevated monoclonal proteins: thirteen with Waldenstrom’s Macroglobulinemia (ten IgM Kappa, three IgM lambda), three with Multiple Myeloma (two IgM, one IgA), two with IgM MGUS, one with IgG MGUS lambda, and one with plasmocytic lymphoma (IgM lambda). Two cases (CMML, astrocytoma) lacked monoclonal protein assessment. No visual differences were seen between IgM kappa and lambda; distinct patterns were noted for IgA, IgG, and lymphoma/astrocytoma. Band interference correlated with monoclonal protein concentration, M-spike, and viscosity. In monitored patients, reduced monoclonal protein after treatment was associated with improved vWF levels and clearer bands (Figure 1, Figure 2). Conclusions
IgM monoclonal proteins caused the most pronounced interference. Clinical improvement and reduced monoclonal proteins correlated with normalized vWF, less banding interference, and AVWS improvement. Further characterization of unique patterns in IgA, IgG, lymphoma, and astrocytoma may inform treatment and early diagnosis. Additional studies are needed to confirm the pathogenic interaction between monoclonal protein and vWF.
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.
Patients with plasma cell dyscrasias may develop acquired von Willebrand syndrome (AVWS), often associated with monoclonal proteins. Mechanisms include antibody-mediated clearance or inhibition of von Willebrand factor (VWF), and, less commonly, non-specific paraprotein/VWF complex formation. In addition to reduced VWF antigen and activity or decreased antigen/activity ratio, the VWF multimer pattern may be distorted. Objectives
This study characterizes laboratory abnormalities in AVWS patients with distorted multimer patterns, illustrating the spectrum of electrophoretic abnormalities (Figure 1). Multimer patterns are further classified by paraprotein type/strength, other causes, and treatment effects (Figure 2). Methods
The Mayo Clinic Coagulation Laboratory information system was searched (2014–2025) for individuals at Mayo Clinic (MN, FL, AZ) with distorted VWF multimer banding; external samples were excluded. Patient charts were reviewed for monoclonal gammopathies, AVWS, and treatment effects. The lab-developed VWF multimer assay demonstrates clear banding of the full VWF multimer range. Results were descriptively analyzed versus controls and known VWD patterns. When repeated, patterns persisted or intensified with x2 dilution (4.7% SDS) if VWF antigen/activity <30%. Similar patterns have been described on a smaller scale. Results
Among 4,040 internal patients evaluated, twenty-two showed significant interference on multimer gels. Of these, twenty had elevated monoclonal proteins: thirteen with Waldenstrom’s Macroglobulinemia (ten IgM Kappa, three IgM lambda), three with Multiple Myeloma (two IgM, one IgA), two with IgM MGUS, one with IgG MGUS lambda, and one with plasmocytic lymphoma (IgM lambda). Two cases (CMML, astrocytoma) lacked monoclonal protein assessment. No visual differences were seen between IgM kappa and lambda; distinct patterns were noted for IgA, IgG, and lymphoma/astrocytoma. Band interference correlated with monoclonal protein concentration, M-spike, and viscosity. In monitored patients, reduced monoclonal protein after treatment was associated with improved vWF levels and clearer bands (Figure 1, Figure 2). Conclusions
IgM monoclonal proteins caused the most pronounced interference. Clinical improvement and reduced monoclonal proteins correlated with normalized vWF, less banding interference, and AVWS improvement. Further characterization of unique patterns in IgA, IgG, lymphoma, and astrocytoma may inform treatment and early diagnosis. Additional studies are needed to confirm the pathogenic interaction between monoclonal protein and vWF.
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.