Flowchart for ADAMTS13 investigation in TTP. ADAMTS13 investigation is mandatory in the management of TMA because it is the unique marker able to definitely establish the diagnosis of TTP. ADAMTS13 activity is always the screening assay to perform. If ADAMTS13 activity is less than 10%, the clinical suspicion of TTP is confirmed. Thus, to document the mechanism for ADAMTS13 severe deficiency, detection of anti-ADAMTS13 IgG is the second-rank assay, whereas ADAMTS13 gene sequencing is a third-rank assay limited to selected indications. Data provided by ADAMTS13 monitoring during follow-up are also important to elucidate the mechanism for ADAMTS13 severe deficiency. In almost all cases, this panel of assays performed during both TTP inaugural episode and follow-up allows us to identify the 3 forms of TTP: acquired autoimmune TTP, acquired TTP of unknown mechanism (apparently not linked to ADAMTS13 autoantibodies), and inherited TTP (USS). In some exceptional cases, however, TTP remains with an unknown etiology.