Von Willebrand disease (VWD) is a bleeding disorder caused by quantitative (type 1 or 3) or qualitative (type 2A/2B/2M/2N) defects of circulating von Willebrand factor (VWF). Circulating VWF levels... Show moreVon Willebrand disease (VWD) is a bleeding disorder caused by quantitative (type 1 or 3) or qualitative (type 2A/2B/2M/2N) defects of circulating von Willebrand factor (VWF). Circulating VWF levels not always fully explain bleeding phenotypes, suggesting a role for alternative factors, like platelets. Here, we investigated platelet factor 4 (PF4) in a large cohort of patients with VWD. PF4 levels were lower in type 2B and current bleeding phenotype was significantly associated with higher PF4 levels, particularly in type 1 VWD. Based on our findings we speculate that platelet degranulation and cargo release may play a role across VWD subtypes. Show less
Blood coagulation is vital for life by reducing blood loss upon injury. One of the key players in the initial steps of coagulation is Von Willebrand Factor (VWF). VWF is mainly produced and stored... Show moreBlood coagulation is vital for life by reducing blood loss upon injury. One of the key players in the initial steps of coagulation is Von Willebrand Factor (VWF). VWF is mainly produced and stored by the cells that line the blood vessels and functions upon secretion by creating a platelet plug at the side of injury. Mutations in VWF can disturb this process, for instance through insufficient VWF secretion, which causes Von Willebrand disease, a hereditary bleeding disorder characterized by prolonged bleeding. As the morphology of VWF is highly related to its functionality, we aimed to obtain more knowledge on the mechanisms that can be affected in Von Willebrand disease by studying the normal lifecycle of VWF using correlative light and electron microscopy (CLEM). CLEM combines fluorescent light microscopy with electron microscopy on the same sample to obtain structural information of specific biological events that are difficult to study with electron microscopy alone. Using CLEM, novel information was obtained regarding the formation of the VWF storage organelle, in addition we also discovered novel pathophysiological mechanisms acting during VWF secretion that may be effectuated in Von Willebrand disease. Show less
Velzen, A.S. van; Peters, M.; Bom, J.G. van der; Fijnvandraat, K. 2014
