Submitted April 5, 2006
Accepted June 21, 2006
Assay of the von Willebrand factor (VWF) propeptide to identify type 1 von Willebrand disease patients with decreased VWF survival
Sandra L Haberichter*, Michael Balistreri, Pamela Christopherson, Patricia Morateck, Stefana Gavazova, Daniel B Bellissimo, Marilyn J. Manco-Johnson, Joan Cox Gill, and Robert R Montgomery
Medical College of Wisconsin; Children's Research Institute; Children's Hospital of WI
BloodCenter of Wisconsin
University of Colorado - Denver and the Health Sciences Center
Medical College of Wisconsin; BloodCenter of Wisconsin
* Corresponding author; email: shaberic{at}mcw.edu.
Type 1 von Willebrand disease (VWD) is characterized by a partial quantitative deficiency of von Willebrand factor (VWF). Few VWF gene mutations have been identified that cause dominant type 1 VWD. The decreased survival of VWF in plasma has recently been identified as a novel mechanism for type 1 VWD. We report four families with moderately severe type 1 VWD characterized by low plasma VWF:Ag and FVIII:C levels, proportionately low VWF:RCo, and dominant inheritance. A decreased survival of VWF in affected individuals was identified with VWF half-lives of 1-3 hours, while the half-life of VWF propeptide (VWFpp) was normal. DNA sequencing revealed a single (heterozygous) VWF mutation in affected individuals, S2179F in two families, and W1144G in two families, neither of which has been previously reported. We demonstrate that the ratio of steady-state plasma VWFpp/VWF:Ag can be utilized to identify patients with a shortened VWF half-life. An increased ratio distinguished affected from unaffected individuals in all families. A significantly increased VWFpp/VWF:Ag ratio together with reduced VWF:Ag may indicate the presence of a true genetic defect and decreased VWF survival phenotype. This phenotype may require an altered clinical therapeutic approach and we propose to refer to this phenotype as type-1C VWD.
