Erythrocytes and von Willebrand factor in venous thrombosis

Venous thromboembolism represents the third leading vascular disease after myocardial infarction and stroke. Erythrocytes, the most abundant cells in venous thrombi, were thought to be innocent bystanders that become tangled up in the fibrin mesh of venous thrombi. However, this thesis describes that erythrocytes can bind to von Willebrand factor and this interaction may contribute to the stabilization and propagation of a venous thrombus. In this thesis, healthy erythrocytes are shown to adhere to endothelial cells, provided that endothelial cells are activated and erythrocytes are exposed to a stimulus that induces a calcium influx. Furthermore, it is described that erythrocytes adhere to ultra large von Willebrand factor strings that are released from activated endothelial cells or to von Willebrand factor that is immobilized on a surface. Erythrocytes bind preferentially to von Willebrand factor and show only minor binding to fibrinogen or other substrates. The adhesion of erythrocytes to von Willebrand factor increases significantly when the wall shear stress approaches stasis. Detailed microscopy imaging demonstrated that erythrocytes, von Willebrand factor, and fibrin show a striking pattern in human venous thrombi by forming erythrocyte-von Willebrand factor-erythrocyte and erythrocyte-von Willebrand factor-fibrin complexes. Furthermore, the link between the ABO blood group system and von Willebrand factor is discussed. The thesis is concluded by a summary and discussion about the erythrocyte-von Willebrand factor interaction and its implications for venous thrombosis.