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Establishing Reference Intervals for von Willebrand Factor Multimers

1North Estonia Medical Centre, Laboratory, Tallinn, Estonia, 2Tallinn University of Technology, Department of Health Technologies, Tallinn, Estonia, 3Foch Hospital, Department of Biology, Suresnes, France, 4Riga Stradins University, Riga, Latvia, 5Riga East University Hospital, Riga, Latvia, 6University of Utah School of Medicine, Department of Pathology, Salt Lake City, United States, 7ARUP Laboratories Institute for Clinical and Experimental Pathology, Salt Lake City, United States, 8Sebia, Research and Developments Department, Lisses, France, 9Vilnius University, Faculty of Medicine, Institute of Biomedical Sciences, Department of Physiology, Biochemistry, Microbiology and Laboratory Medicine, Vilnius, Lithuania

Abstract Number: PB1574

Meeting: ISTH 2020 Congress

Theme: Platelet Disorders and von Willebrand Disease » VWF and von Willebrand Factor Disorders - Clinical Conditions

Background: von Willebrand factor multimers (VWF:MM) methodologies are technically difficult, laborious, time consuming, non-standardized and results vary between labs. A first step towards standardization was made by introducing a semi‐automated VWF:MM assay by Sebia (Lisses, France). In addition to qualitative interpretation of multimer patterns, the Sebia PHORESIS software allows quantification of VWF:MM band patterns, thus the percentage of each molecular weight multimer fraction can be calculated. Due to lack of reference values for VWF:MM fractions, results interpretation can be challenging in some cases.

Aims: The aim of this study was to determine reference intervals for low molecular weight (LMW), intermediate molecular weight (IMW) and high molecular weight (HMW) multimers.

Methods: To collect a larger sample size an international cooperation was initiated. We analyzed data from 134 participants (51 males and 83 non-pregnant females) aged 17-69 years. Acceptance criteria: no history of hemorrhagic episodes; no usage of any medication for at least 10 days before blood collection; normal coagulation screening tests; normal VWF screening assay results; written consent provided.
Reference intervals (with 90% confidence intervals) were calculated using a robust method according to the CLSI C28-A3 standard. The study was performed according to the Declaration of Helsinki and was approved by national ethical committees.

Results: After outlier exclusion (n=3), done by Grubs double sided and Tukey methods, a total of 131 samples were analyzed statistically. Results were normally distributed. No significant differences were found between males and females. The proposed reference intervals for VWF:MM are presented in table 1.

  Low Molecular Weight Intermediate Molecular Weight High Molecular Weight
Lower limit, % [90% CI] 10.42 [9.94 – 10.95] 22.55 [21.81 – 23.32] 45.58 [44.54 – 46.71]
Upper limit, % [90% CI] 22.52 [21.52 – 23.51] 37.57 [36.44 – 38.72] 66.59 [65.10 – 68.02]

[Table 1. Proposed reference intervals for VWF:MM]

Conclusions: Quantification of VWF:MM fractions, in addition to qualitative assessment of VWF:MM patterns, has potential value to aid in differential diagnosis of VWD sub-types. The reference values calculated in this study can be used in future research to establish clinical decision liimits.

To cite this abstract in AMA style:

Pikta M, Vasse M, Lejniece S, Smock KJ, Moser KA, Bautista H, Nouadje G, Banys V. Establishing Reference Intervals for von Willebrand Factor Multimers [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/establishing-reference-intervals-for-von-willebrand-factor-multimers/. Accessed June 22, 2021.

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