Cellular mechanisms are difficult to study in non-human primates and mouse models do not develop the coagulopathy of HUS, so the current study with human cells extends the in vivo observations by demonstrating in vitro loss of EPCR and TM surface expression on endothelial cells due to Stx and DAMPs, particularly histones, and reduced capacity to generate APC. This evidence concerns the gene PROCR and hemolytic-uremic syndrome.