Rienk Nieuwland, Jillian W P Bracht, Joost C M Meijers, Johannes Thaler
This guide provides an overview of information that is needed to understand and study the coagulant functions of extracellular vesicles (EVs) in human body fluids. Although EV research has expanded rapidly, the physiological functions of EVs remain incompletely understood, and coagulation is one of the first biological functions that was attributed to EVs. Since coagulation is a complex balance between coagulation promoting and inhibiting pathways, for clarity and to reduce complexity we focus exclusively on how EVs contribute to coagulation-promoting pathways in physiological conditions. We explain what coagulation is, and how coagulation contributes to haemostasis and host defence, followed by an overview of historical evidence showing that extracellular vesicles initiate and promote coagulation. In addition, we explain how extracellular vesicles provide a coagulation-promoting surface, and expand the classical "envelope model". Finally, we summarize how the procoagulant activities of EVs can be measured, and provide guidance to improve the reproducibility of such measurements.