Soracha E. Ward

Enhanced α2-3–linked sialylation determines the extended half-life of CHO-rVWF

Ciara Byrne, Soracha E. Ward, Jamie M. O’Sullivan, Alain Chion et autres

ABSTRACT: The half-life of recombinant human von Willebrand factor (rVWF) expressed in CHO cells (CHO-rVWF; Vonicog alfa; and Vonvendi/Veyvondi) is significantly longer than that of plasma-derived VWF (pdVWF). This finding is intriguing because CHO cells do not generate α2-6 sialylation, which constitutes …

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OC 08.4 Aptamer BT200 Prolongs VWF Half-Life by Blocking Interaction with Macrophage Scavenger Receptor LRP1

Alain Chion, Sonia Águila, Judicaël Fazavana, Chloe Byrne et autres

The pegylated aptamer BT200 binds to the A1 domain of VWF and significantly prolongs VWF half-life in vivo. Although the mechanism(s) involved have not been defined, the LRP1 scavenger receptor binds to the VWF A1 domain and contributes to physiological VWF clearance. …

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VWF–ADAMTS13 axis dysfunction in children with sickle cell disease treated with hydroxycarbamide vs blood transfusion

Helen Fogarty, Azaz Ahmad, Ferdows Atiq, Dearbhla Doherty et autres

Previous studies have reported elevated von Willebrand factor (VWF) levels in patients with sickle cell disease (SCD) and demonstrated a key role for the VWF-ADAMTS13 axis in the pathobiology of SCD vaso-occlusion. Although blood transfusion is the gold standard for stroke prevention …

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Elevated von Willebrand factor levels in multiple myeloma: dysregulated mechanisms of both secretion and clearance

Claire Comerford, Sukhraj Pal Singh Dhami, Philip Thomas Murphy, Sean Patmore et autres

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Macrophage Galactose Lectin Contributes to the Regulation of FVIII (Factor VIII) Clearance in Mice—Brief Report

Soracha E. Ward, Thomas Guest, Ciara Byrne, Patrícia das Dores Lopes et autres

Background: Although most plasma FVIII (Factor VIII) circulates in complex with VWF (von Willebrand factor), a minority (3%–5%) circulates as free-FVIII, which is rapidly cleared. Consequently, 20% of total FVIII may be cleared as free-FVIII. Critically, the mechanisms of free-FVIII clearance remain …

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Endothelial cell activation, Weibel-Palade body secretion, and enhanced angiogenesis in severe COVID-19

Ellie Karampini, Helen Fogarty, Stephanie Elliott, Hannah Morrin et autres

Background Severe COVID-19 is associated with marked endothelial cell (EC) activation that plays a key role in immunothrombosis and pulmonary microvascular occlusion. However, the biological mechanisms through which SARS-CoV-2 causes EC activation and damage remain poorly defined. Objectives We investigated EC activation …

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Blood Transfusion Ameliorates Free Haem-Induced Loss of Thrombomodulin and Endothelial Cell Activation in Paediatric Sickle Cell Anaemia

Helen Fogarty, Soracha E. Ward, Ellie Karampini, Azaz Ahmad et autres

Background Sickle cell anaemia (SCA) is responsible for major paediatric morbidity including risk of stroke in up to 10% of children. Mainstays of therapy include hydroxyurea (HU) and chronic blood transfusion (BT), with BT considered gold standard for stroke prevention. However, the …

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von Willebrand factor links primary hemostasis to innate immunity

Clive Drakeford, Sonia Águila, Fiona M. Roche, Karsten Hokamp et autres

The plasma multimeric glycoprotein von Willebrand factor (VWF) plays a critical role in primary hemostasis by tethering platelets to exposed collagen at sites of vascular injury. Recent studies have identified additional biological roles for VWF, and in particular suggest that VWF may …

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Sustained VWF-ADAMTS-13 axis imbalance and endotheliopathy in long COVID syndrome is related to immune dysfunction

Helen Fogarty, Soracha E. Ward, Liam Townsend, Ellie Karampini et autres

BACKGROUND: Prolonged recovery is common after acute SARS-CoV-2 infection; however, the pathophysiological mechanisms underpinning Long COVID syndrome remain unknown. VWF/ADAMTS-13 imbalance, dysregulated angiogenesis, and immunothrombosis are hallmarks of acute COVID-19. We hypothesized that VWF/ADAMTS-13 imbalance persists in convalescence together with endothelial cell …

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Persistent endotheliopathy in the pathogenesis of long COVID syndrome ‐ Reply to comment from von Meijenfeldt et al.

Helen Fogarty, Ellie Karampini, Andrew S. O’Donnell, Soracha E. Ward et autres

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Persistent endotheliopathy in the pathogenesis of long COVID syndrome

Helen Fogarty, Liam Townsend, Hannah Morrin, Azaz Ahmad et autres

BACKGROUND: Persistent symptoms including breathlessness, fatigue, and decreased exercise tolerance have been reported in patients after acute SARS-CoV-2 infection. The biological mechanisms underlying this "long COVID" syndrome remain unknown. However, autopsy studies have highlighted the key roles played by pulmonary endotheliopathy and …

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The Biological Significance of von Willebrand Factor O-Linked Glycosylation

Soracha E. Ward, Jamie M. O’Sullivan, James S. O’Donnell

Glycosylation is a key posttranslational modification, known to occur on more than half of all secreted proteins in man. As such, the role of N- and O-linked glycan structures in modulating various aspects of protein biology is an area of much research. …

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