Linked Life Data

18449422

Source:http://linkedlifedata.com/resource/pubmed/id/18449422

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2008-5-1
pubmed:abstractText
Reduced plasma survival of von Willebrand factor (VWF) may contribute towards the pathogenesis of type 1 von Willebrand disease (VWD). However, little is known about mechanism(s) of VWF clearance and factors that may affect it. The half-life of VWF-related parameters following the administration of DDAVP was measured in 26 patients with type 1 VWD and 10 haemophilia A controls. Binding of lectins Ricinus communis (RCA-I) and Erythina crystagalli (ECA) agglutinins to VWF and VWF susceptibility to ADAMTS-13-mediated proteolysis were investigated. Sequence analysis of targeted regions of the VWF gene was performed to inspect for mutations that have been associated with increased clearance. Post-DDAVP clearance of VWF was increased approximately three-fold in the type 1 VWD cohort overall. However this was not shown to consistently associate with steady-state VWF antigen (VWF:Ag) levels. Furthermore, increased VWF clearance was not consistently associated with increased ratios of VWF propeptide (VWFpp) to VWF:Ag indicating that a normal ratio does not necessarily reflect normal post-DDAVP survival in type 1 VWD patients. RCA-I and ECA binding to VWF were increased in type 1 VWD patients and, although inversely correlated with VWF levels, this was independent of VWF clearance. There was no association between VWF clearance and ADAMTS-13-mediated proteolysis. Three novel candidate mutations with an increased clearance phenotype were identified. The data are consistent with heterogeneity in pathogenic mechanisms in type 1 VWD and are consistent with type 1 VWD representing a complex genetic trait.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0340-6245
pubmed:author
pubmed:issnType
Print
pubmed:volume
99
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
916-24
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18449422-ADAM Proteins, pubmed-meshheading:18449422-Cohort Studies, pubmed-meshheading:18449422-DNA Mutational Analysis, pubmed-meshheading:18449422-Deamino Arginine Vasopressin, pubmed-meshheading:18449422-Female, pubmed-meshheading:18449422-Genetic Predisposition to Disease, pubmed-meshheading:18449422-Genotype, pubmed-meshheading:18449422-Glycosylation, pubmed-meshheading:18449422-Half-Life, pubmed-meshheading:18449422-Hemostatics, pubmed-meshheading:18449422-Humans, pubmed-meshheading:18449422-Infusions, Intravenous, pubmed-meshheading:18449422-Male, pubmed-meshheading:18449422-Mutation, pubmed-meshheading:18449422-Phenotype, pubmed-meshheading:18449422-Plant Lectins, pubmed-meshheading:18449422-Protein Binding, pubmed-meshheading:18449422-Protein Precursors, pubmed-meshheading:18449422-Protein Processing, Post-Translational, pubmed-meshheading:18449422-Treatment Outcome, pubmed-meshheading:18449422-von Willebrand Diseases, pubmed-meshheading:18449422-von Willebrand Factor
pubmed:year
2008
pubmed:articleTitle
Survival of von Willebrand factor released following DDAVP in a type 1 von Willebrand disease cohort: influence of glycosylation, proteolysis and gene mutations.
pubmed:affiliation
Katharine Dormandy Haemophilia Centre and Thrombosis Unit, Department of Haematology, Royal Free Campus, University College and Royal Free Medical School, London, United Kingdom. E-mail: c.millar@medsch.ucl.ac.uk
pubmed:publicationType
Journal Article, Controlled Clinical Trial