PATHOPHYSIOLOGY OF VON WILLEBRAND FACTOR IN BLEEDING AND THROMBOSIS
type: CreativeWork
description: von Willebrand factor (VWF) is a multimeric glycoprotein mainly known to be involved in primary hemostasis recruiting platelets at the site of damaged vessels and acting as factor VIII (FVIII) carrier. Quantitative or qualitative alteration of VWF protein is responsible for von Willebrand disease (VWD). Conversely, increased VWF levels have been found to be associated to different thrombotic disorders such as arterial thrombosis, ischemic stroke and venous thromboembolisms. The dual role of VWF in both bleeding and thrombosis, with a focus on VWD and deep vein thrombosis (DVT), are discussed in this thesis. In the first part, we described the approach used to perform VWD diagnosis, including the use of in silico tools and heterologous cell systems to confirm the disease-causing role of VWF variants. In Chapter 2, we described the approach used to perform a differential diagnosis between type 2A and 2B VWD in a pediatric patient carrying a de novo and novel variant. The biochemical characterization allowed us to exclude type 2M due to a loss of high molecular weight multimers and reduced VWF:CB. The finding of a novel deletion, despite its localization in the A2 domain, did not allow for discrimination between type 2A and 2B VWD. The conventional approach would require to perform the ristocetin-induced platelet aggregation (RIPA) to discriminate type 2B VWD from the other type 2. This assay needs a relatively large amount of fresh blood, which is especially undesirable in the case of a pediatric patient. Therefore, we opted for an alternative approach using a platelet-dependent VWF activity (VWF:GPIbM) ELISA. This assay is able to discriminate type 2B VWD patients from the other type 2 VWD patients and it can be done using a small amount of frozen plasma sample. This led us to confirm that our patient was affected by type 2A VWD. In Chapters 3 and 4, we combined the use of predictive in silico tools and heterologous cell systems to prove the pathogenic role of the VW…
abstract: von Willebrand factor (VWF) is a multimeric glycoprotein mainly known to be involved in primary hemostasis recruiting platelets at the site of damaged vessels and acting as factor VIII (FVIII) carrier. Quantitative or qualitative alteration of VWF protein is responsible for von Willebrand disease (VWD). Conversely, increased VWF levels have been found to be associated to different thrombotic disorders such as arterial thrombosis, ischemic stroke and venous thromboembolisms. The dual role of VWF in both bleeding and thrombosis, with a focus on VWD and deep vein thrombosis (DVT), are discussed in this thesis. In the first part, we described the approach used to perform VWD diagnosis, including the use of in silico tools and heterologous cell systems to confirm the disease-causing role of VWF variants. In Chapter 2, we described the approach used to perform a differential diagnosis between type 2A and 2B VWD in a pediatric patient carrying a de novo and novel variant. The biochemical characterization allowed us to exclude type 2M due to a loss of high molecular weight multimers and reduced VWF:CB. The finding of a novel deletion, despite its localization in the A2 domain, did not allow for discrimination between type 2A and 2B VWD. The conventional approach would require to perform the ristocetin-induced platelet aggregation (RIPA) to discriminate type 2B VWD from the other type 2. This assay needs a relatively large amount of fresh blood, which is especially undesirable in the case of a pediatric patient. Therefore, we opted for an alternative approach using a platelet-dependent VWF activity (VWF:GPIbM) ELISA. This assay is able to discriminate type 2B VWD patients from the other type 2 VWD patients and it can be done using a small amount of frozen plasma sample. This led us to confirm that our patient was affected by type 2A VWD. In Chapters 3 and 4, we combined the use of predictive in silico tools and heterologous cell systems to prove the pathogenic role of the VW…
author: PAGLIARI, MARIA TERESA
language: eng
keywords: von Willebrand factor, von Willebrand disease, ADAMTS13 human protein, Deep vein thrombosi, Factor VIII, bleeding, gene mutations propeptide, alloantibodie, in vitro expression studies, Settore MED/09 - Medicina Interna
date published: 2023-09-20
date modified: 2026-07-27T20:19:00Z
provider: Università degli Studi di Milano
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Università degli Studi di Milano

PropertyValue
property ID: Handle
value: https://hdl.handle.net/2434/1000488

PropertyValue
property ID: DOI
value: 10.13130/pagliari-maria-teresa_phd2023-09-20