Establishing Reference Intervals for von Willebrand Factor Multimers

M. Pikta^1,2, M. Vasse³, S. Lejniece^4,5, K.J. Smock^6,7, K.A. Moser^6,7, H. Bautista⁸, G. Nouadje⁸, V. Banys⁹

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 October 2, 2023.

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