Detailed von Willebrand factor multimer analysis in patients with von Willebrand disease in the European study, molecular and clinical markers for the diagnosis and management of type 1 von Willebrand disease (MCMDM-1VWD)

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Background: Type 1 von Willebrand disease (VWD) is a congenital bleeding disorder characterized by a partial quantitative deficiency of plasma von Willebrand factor (VWF) in the absence of structural and/or functional VWF defects. Accurate assessment of the quantity and quality of plasma VWF is difficult but is a prerequisite for correct classification. Objective: To evaluate the proportion of misclassification of patients historically diagnosed with type 1 VWD using detailed analysis of the VWF multimer structure. Patients and methods: Previously diagnosed type 1 VWD families and healthy controls were recruited by 12 expert centers in nine European countries. Phenotypic characterization comprised plasma VWF parameters and multimer analysis using low- and intermediate-resolution gels combined with an optimized visualization system. VWF genotyping was performed in all index cases (ICs). Results: Abnormal multimers were present in 57 out of 150 ICs; however, only 29 out of these 57 (51%) had VWF ristocetin cofactor to antigen ratio below 0.7. In most cases multimer abnormalities were subtle, and only two cases had a significant loss of the largest multimers. Conclusions: Of the cases previously diagnosed as type 1 VWD, 38% showed abnormal multimers. Depending on the classification criteria used, 22 out of these 57 cases (15% of the total cohort) may be reclassified as type 2, emphasizing the requirement for multimer analysis compared with a mere ratio of VWF functional parameters and VWF:Ag. This is further supported by the finding that even slightly aberrant multimers are highly predictive for the presence of VWF mutations.


  • U Budde
  • R Schneppenheim
  • J Eikenboom
  • A Goodeve
  • K Will
  • E Drewke
  • G Castaman
  • F Rodeghiero
  • A B Federici
  • J Batlle
  • A Perez
  • D Meyer
  • C Mazurier
  • J Goudemand
  • J Ingerslev
  • D Habart
  • Z Vorlova
  • Stefan Lethagen
  • J Pasi
  • F Hill
  • I Peake
Enheter & grupper

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Kardiologi


Sidor (från-till)762-771
TidskriftJournal of Thrombosis and Haemostasis
StatusPublished - 2008
Peer review utfördJa