The decreased survival of von Willebrand factor (VWF) in plasma has been implicated as a mechanism in a subset of type 1 von Willebrand disease (VWD) patients. We have previously reported that the ratio of plasma levels of VWF and its propep- tide (VWFpp) can be used to identify patients with reduced VWF survival. In this study, we report the assay of VWFpp and VWF:Ag in 19 individuals recruited from 6 European centers within the MC- MDM-1VWD study. Eight individuals had a VWF:Ag level less than 30 IU/dL. Seven of these patients had a robust desmopressin response and significantly reduced VWF half-life that was predicted by a markedly increased steady-state plasma VWFpp/VWF:Ag ratio. VWF mutations previously associated with reduced VWF survival were identified in each of the 7 individuals. Thus, a substantially increased ratio of steady-state VWFpp/ VWF:Ag predicted a reduced VWF half- life in patients with markedly decreased VWF:Ag levels. These data indicate that a reduced VWF survival is found in a sub- population of patients with type 1 VWD. The systematic assay of both plasma VWF and the VWF propeptide in moderately severe type 1 VWD patients may identify patients with a reduced VWF survival phenotype.
|Titolo:||Identification of type 1 von Willebrand disease patients with reduced von Willebrand factor survival by assay of the VWF propeptide in the European study: molecular and clinical markers for the diagnosis and management of type 1 VWD (MCMDM-1VWD)|
|Autori interni:||FEDERICI, AUGUSTO BRAMANTE|
|Parole Chiave:||von Willebrand-factor multimers; Wibel-palade bodies; factor gene; quantitative-analysis; candidate mutation; R1205H mutation; families; genotype; Vicenza; phenotype|
|Settore Scientifico Disciplinare:||Settore MED/15 - Malattie del Sangue|
|Data di pubblicazione:||2008|
|Digital Object Identifier (DOI):||10.1182/blood-2007-09-110940|
|Appare nelle tipologie:||01 - Articolo su periodico|