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Thank you for attending THSNA 2026. The virtual meeting is now closed.
Presentation Details
| Limitation of Automated Von Willebrand Testing in Identifying a Case of Acquired Von Willebrand Syndrome Shannon Goodall, Maissaa Janbain. Section of Hematology and Medical Oncology, Tulane School of Medicine, New Orleans, LA, USA |
Abstract
Acquired von Willebrand syndrome (aVWS) is a rare but underrecognized bleeding disorder characterized by deficient or defective von Willebrand factor (WF) that develops secondary to an underlying condition (e.g. malignancies especially lymphoproliferative, autoimmune disorders, and cardiovascular pathologies)1. Diagnosis can be challenging and may require a comprehensive assessment, including VWF antigen levels and multiple activity assays evaluating its different functional roles. Due to test limitations, repeat or specialized testing is sometimes needed to confirm the disorder2. Numerous assays have been developed and validated, and many antigen and activity assays are now performed using automated testing such as latex immunoassays3. However, interference from heterophile antibodies such as rheumatoid factor has been reported and can further complicate interpretation of test results4,5. Case Summary: A 56 year-old female with a history of depression and bariatric surgery presented with a three-month history of easy bruising and mucocutaneous bleeding. She had a history of heavy but regular menses until menopause and a recent post-operative bleed requiring blood transfusion after gastric sleeve surgery. She denied personal or family history of a bleeding disorder. Physical exam notable for faint systolic murmur, palpable left axillary lymph node. Initial laboratory testing: aPTT was prolonged (56s, ref 24-37) and did not correct with mixing study. Lupus anticoagulant was detected. FVIII activity was decreased (24%, ref 50-150), and confirmed on chromogenic FVIII assay (36%, ref 50-150). VWF:Ag was elevated (126 IU/dL, ref 37-118) with normal VWF:GP1bM (85 IU/dL, ref 50-180) and a 0.67 ratio. Genetic evaluation for hemophilia A was negative and VWD type 2N binding assay was normal (98%). VWF multimer analysis showed loss of high molecular weight multimers. VWF propeptide (VWFpp) was 200 IU/dL(ref 56-140) with VWFpp/Ag ratio slightly elevated at 1.58. Additionally, VWF:collagen binding assay showed reduced activity with VWF:CIII 19 IU/dL (ref 50-203), VWF:CIV 35 IU/dL (ref 49-180) and VWF:Ag as part of this panel was reported at 47 IU/dL. This raised concerns for heterophile antibody interference in the automated assays causing the discrepant results, so rheumatoid factor was obtained and found to be elevated at 28 IU/ml (ref <20). Repeat testing was performed using manual ELISA-based tests: VWF:Ag 47 IU/dL (ref: 50-188), VWF:GP1bM 17 IU/dL (ref: 50-180) with ratio 0.36. VWF inhibitor panel was negative. These results confirmed diagnosis of aVWS. She underwent further evaluation to identify an underlying disorder related to aVWS including a negative cardiology assessment and a lymph node biopsy, which was consistent with small lymphocytic leukemia (SLL/CLL). She received continuous infusion with plasma derived VWF concentrate during her biopsy with no noted bleeding complications. Discussion: This case underscores the need to maintain a high index of suspicion for aVWS when the clinical picture is consistent despite discordant laboratory findings. Although the increasingly used automated assays offer rapid results, they should be interpreted with caution and confirmed with manual methods when clinically indicated. In this instance, conflicting results in the setting of new-onset bleeding prompted careful review of the testing methodology and further investigation, ultimately leading to ELISA-based confirmation of von Willebrand syndrome.
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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.