VWF propeptide and ratios between VWF, VWF propeptide, and FVIII in the characterization of type 1 von Willebrand disease.

Abstract

During posttranslational modifications of von Willebrand factor (VWF), the VWF propeptide (VWFpp) is cleaved. The ratio between VWFpp and VWF antigen (VWF:Ag) and the ratio between factor VIII (FVIII:C) and VWF:Ag may be used to assess synthesis and clearance of VWF. We analyzed the contribution of VWFpp and ratios of VWFpp/VWF:Ag and FVIII:C/VWF:Ag in the pathophysiological characterization of type 1 von Willebrand disease (VWD) in the Molecular and Clinical Markers for the Diagnosis and Management of Type 1 VWD (MCMDM-1VWD) study. The VWFpp/VWF:Ag and FVIII:C/VWF:Ag ratios were increased among patients compared with unaffected family members and healthy controls. The VWFpp/VWF:Ag ratio was higher in individuals heterozygous for missense mutations than in those heterozygous for null alleles. In contrast, the FVIII:C/VWF:Ag ratio was highest among heterozygotes for VWF null alleles. The ratios of VWFpp/VWF:Ag and FVIII:C/VWF:Ag indicate that the pathophysiological mechanisms of type 1 VWD include reduced production and accelerated clearance of VWF, but that often a combination of both mechanisms is implicated.

• Authors: Jeroen Eikenboom, Augusto B Federici, Richard J Dirven, Giancarlo Castaman, Francesco Rodeghiero, Ulrich Budde, Reinhard Schneppenheim, Javier Batlle, Maria Teresa Canciani, Jenny Goudemand, Ian Peake, Anne Goodeve, MCMDM-1VWD Study Group
• Journal: Blood (Blood) Vol. 121 Issue 12 Pg. 2336-9 (Mar 21 2013) ISSN: 1528-0020 [Electronic] United States
• PMID: 23349392 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Protein Precursors
• von Willebrand Factor
• Factor VIII

Topics

• Case-Control Studies
• Cohort Studies
• Factor VIII (analysis, genetics)
• Family
• Genetic Carrier Screening
• Genetic Linkage
• Humans
• Mutation (physiology)
• Protein Multimerization
• Protein Precursors (blood, chemistry, genetics, metabolism)
• Protein Processing, Post-Translational (genetics)
• von Willebrand Disease, Type 1 (blood, diagnosis, genetics)
• von Willebrand Factor (analysis, chemistry, genetics, metabolism)