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Updated: May 31, 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

Expanded phenotype-genotype correlations in a pediatric population with type 1 von Willebrand disease

J D Robertson1, P R Yenson, M L Rand

  • 1Haematology Service, Division of Oncology, Royal Children's Hospital Department of Haematology, Pathology Queensland, Brisbane, QLD, Australia. jeremy_robertson@health.qld.gov.au

Journal of Thrombosis and Haemostasis : JTH
|June 30, 2011
PubMed

Insights

This study reveals that increased von Willebrand factor (VWF) clearance and intracellular retention are key mechanisms in pediatric type 1 von Willebrand disease (VWD). Some patients also show reduced VWF mRNA, indicating additional contributing factors.

Area of Science:

  • Hematology
  • Genetics
  • Pediatric Medicine

Background:

  • Type 1 von Willebrand disease (VWD) pathophysiology is increasingly understood through phenotype-genotype studies.
  • No prior studies have exclusively focused on a pediatric cohort with type 1 VWD.

Purpose of the Study:

  • To investigate phenotype-genotype correlations in pediatric patients diagnosed with type 1 VWD.
  • To utilize first-degree family members as controls for comparison.

Main Methods:

  • Comprehensive phenotypic assessment including von Willebrand factor (VWF) levels and function assays.
  • Bleeding scores, desmopressin response, VWF propeptide (VWFpp) levels, and platelet-derived VWF mRNA levels were analyzed.

Main Results:

  • Fourteen VWF mutations were identified in 17 of 23 pediatric index cases (aged 5-17 years), including four novel mutations.
  • Lower VWFpp levels were observed in index cases compared to controls (median 49 vs. 86 U dL(-1)).
  • A VWFpp/VWF antigen ratio > 1.6 was noted in most patients with suboptimal desmopressin response, particularly those with R1205H and R1315C mutations. Reduced VWF mRNA was found in patients with nonsense mutations.

Conclusions:

  • Increased VWF clearance and intracellular retention are significant mechanisms in pediatric type 1 VWD.
  • Nonsense-mediated decay of mutant mRNA transcripts may contribute to VWD in some pediatric patients.
  • The R1315C mutation exhibits a variable phenotype, and VWFpp warrants further investigation as a marker for VWF biosynthesis and release.
Abstract

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