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Title: Investigation of determinants of clearance of von Willebrand Factor in individuals with type 1 VWD
Author: Millar, C. M.
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2008
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The release and clearance of von Willebrand Factor (VWF) in a group of patients with the quantitative deficiency type 1 von Willebrand Disease (VWD) was investigated. This was done by analysis of circulating VWF and VWF released from the endothelial pool on infusion of a vasopressin analogue. A variety of parameters were investigated pre-and post infusion in order to identify VWF gene linked and non-linked variables that could affect VWF clearance. Increased clearance of plasma VWF in a significant proportion of type 1 VWD patients was shown but this was not consistently associated with steady-state levels of VWF, indicating that circulating plasma VWF levels are not a consistent reflection of the VWF life-cycle in this patient group. An association between galactose exposure and reduced levels of VWF was demonstrated by the increased binding of the lectins Ricinus communis and Erythina crystagalli, this was unrelated to clearance. In addition, no significant ABO blood group effect on VWF clearance was demonstrated. The absolute level of ADAMTS-13, and the susceptibility of VWF to cleavage by ADAMTS-13 were not associated with the clearance rate of VWF in patients with type 1 VWD. Three novel candidate mutations were identified in association with significantly accelerated VWF clearance. Notably, candidate mutations were generally identified in patients with steady-state VWF levels reduced to <20 IUdL"1 and family analysis suggests absolute linkage with the VWF gene. Despite demonstrating an increased rate of clearance in the majority of patients with type 1 VWD, no single underlying common characteristic or variable was predominant within this study group.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available