An IL-1–induced amplification loop in TTP. Release of ultralarge multimers in the absence of ADAMTS13 activity results in formation of platelet aggregates and microthrombi, causing ischemic injuries. This TTP-induced ischemia triggers the release of proinflammatory cytokines, such as IL-1, that can initiate damage, leading to amplification of disease severity. Anakinra-based IL-1 blockade is an appealing treatment that has been used effectively for a variety of autoimmune and inflammatory disease states and is effective in mitigating many pathophysiological features of TTP.