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Updated: Jun 25, 2026

Investigating von Willebrand Factor Pathophysiology Using a Flow Chamber Model of von Willebrand Factor-platelet String Formation
08:30

Investigating von Willebrand Factor Pathophysiology Using a Flow Chamber Model of von Willebrand Factor-platelet String Formation

Published on: August 14, 2017

Genetic alteration of the D2 domain abolishes von Willebrand factor multimerization and trafficking into storage

S L Haberichter1, A M Allmann, M A Jozwiak

  • 1Department of Pediatrics, Medical College of Wisconsin, and Children's Research Institute, Children's Hospital of Wisconsin, Milwaukee, WI 53226, USA. shaberic@mcw.edu

Journal of Thrombosis and Haemostasis : JTH
|February 5, 2009
PubMed
Abstract

Insights

A mutation in the von Willebrand factor (VWF) propeptide causes defects in VWF processing and storage. Surprisingly, normal VWF can partially restore function in trans, suggesting a broader role for VWFpp.

Area of Science:

  • Hematology
  • Molecular Biology
  • Protein Biochemistry

Background:

  • The von Willebrand factor (VWF) propeptide (VWFpp) is crucial for mature VWF protein multimerization and storage.
  • Mutations affecting VWF multimerization are known in von Willebrand disease, but their impact on VWF regulated storage is less understood.

Purpose of the Study:

  • To investigate the functional consequences of a specific VWF gene mutation on VWF processing, multimerization, and storage.
  • To explore the role of VWFpp in the regulated storage of VWF.

Main Methods:

  • Identified a heterozygous in-frame deletion in exon 12 of the VWF gene, leading to the loss of amino acids 436-442 in VWFpp.
  • Utilized expression studies to analyze the secretion, multimerization, and storage of the variant VWF.

Main Results:

  • The identified VWF variant exhibited reduced secretion, loss of VWF multimerization, and defective regulated storage.
  • Defective storage was linked to impaired propeptide storage due to a faulty sorting signal on VWFpp.
  • Coexpression of wild-type VWF or VWFpp partially restored multimerization of the variant VWF in trans.

Conclusions:

  • A six-amino acid deletion in VWFpp causes significant defects in VWF processing, storage, and overall function.
  • VWFpp can influence VWF multimerization from a variant allele in trans, indicating a potential non-homotypic function.

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