Quantitative 3D microscopy highlights altered von Willebrand factor α‐granule storage in patients with von Willebrand disease with distinct pathogenic mechanisms
Maurice Swinkels, Ferdows Atiq, Petra E. Bürgisser, Johan A. Slotman, Adriaan B. Houtsmuller, Cecilia de Heus, Judith Klumperman, Frank W.G. Leebeek, Jan Voorberg, A.J. Gerard Jansen, Ruben Bierings
Abstract
BACKGROUND: Platelets play a key role in hemostasis through plug formation and secretion of their granule contents at sites of endothelial injury. Defects in von Willebrand factor (VWF), a platelet α-granule protein, are implicated in von Willebrand disease (VWD), and may lead to defective platelet adhesion and/or aggregation. Studying VWF quantity and subcellular localization may help us better understand the pathophysiology of VWD. OBJECTIVE: Quantitative analysis of the platelet α-granule compartment and VWF storage in healthy individuals and VWD patients. PATIENTS/METHODS: Structured illumination microscopy (SIM) was used to study VWF content and organization in platelets of healthy individuals and patients with VWD in combination with established techniques. RESULTS: .C1190 in comparison to VWF in plasma. CONCLUSIONS: Our findings highlight the utility of quantitative imaging approaches in assessing platelet granule content, which may help to better understand VWF storage in α-granules and to gain new insights in the etiology of VWD.