VWF domain structure and potential lateral association. (A) VWF domain structure. ProVWF forms disulfide-linked dimers (B) that further multimerize covalently to multimers in the Golgi (C). These multimers are packaged in the storage granule Weibel-Palade body of endothelial cells (D), where the multimerization process is likely to continue, but factors that regulate its rate and termination remain largely unknown. The stored VWF multimers are released from endothelial cells that are activated by inflammatory stimuli. These newly released VWF multimers form fibrillary meshes that capture platelets (E) and are proteolytically released from the surface of endothelial cells by ADAMTS-13 (F).