Online PhD conferral mrs. Lisa N. van der Vorm
Supervisor: prof.dr. H. ten Cate
Co-supervisors: dr. B. de Laat, dr. J.A. Remijn (Gelre Ziekenhuis, Apeldoorn; Meander Medisch Centrum, Amersfoort)
Key words: active Von Willebrand Factor, platelets, coagulation, thrombosis, bleeding
"Unraveling von Willebrand Factor: Active von Willebrand Factor in conditions of (un)balanced haemostasis"
Von Willebrand factor (VWF) plays an important role in blood clotting. Normally, VWF is in a folded, inactive form in the blood. Due to damage to the blood vessel wall, VWF unfolds to become active. This allows platelets to bind to VWF and a clot forms, which stops the bleeding. Unfortunately, there are various conditions and diseases in which there is an unnecessary amount of active VWF in the blood, which can lead to spontaneous blood clots. This can result in thrombosis in the veins or arteries. The aim of this thesis was to investigate which factors contribute to changes in the amount of circulating active VWF and its interaction with platelets. First, a laboratory test was developed to specifically measure the active fraction of VWF in the blood. It was found that the amount of active VWF in the blood of healthy individuals varies, and increases with intensive exercise, while repeated exercise attenuates this effect. It was then showed that the amount of active VWF in the blood of patients with COPD and chronic kidney disease is increased, and that this is related to the degree of inflammation and the severity of the disease. The findings show that quantifying active VWF in blood can provide information about the underlying causes of an increased risk of thrombosis. Future clinical outcome studies will be necessary to determine the added value of active VWF in addition to existing VWF tests as a biomarker for cardiovascular disease, in the diagnosis and / or monitoring of therapy.
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