Known and unknown players involved in TTP. Among the known players involved in TTP occurrence, ADAMTS13 severe deficiency, either acquired via specific autoantibodies or inherited via ADAMTS13 gene mutations, is the only causing factor identified so far. Other factors are well established as predisposing factors for acquired TTP (ie, female sex, black ethnicity, HLA-DRB1*11, and obesity). Also, pathophysiological conditions increasing plasma VWF levels such as inflammation, sepsis, or pregnancy are known to potentially act as precipitating factors of acute episodes of either acquired or inherited TTP. Other still unknown players are suspected to be involved in TTP occurrence: these may be either proteins of the ADAMTS13/VWF system or cellular candidates such as platelets or endothelial cells.