Diagnostic and treatment advances have revolutionized the landscape of immune-mediated thrombotic thrombocytopenic purpura (iTTP). With the widespread availability of ADAMTS13 testing and novel therapies, outcomes based primarily on platelet counts are no longer sufficient. Clinical definitions have recently been updated to reflect this progress. Given the efficacy of preemptive rituximab in preventing clinical relapses, experts now recommend every 3-month monitoring of ADAMTS13 in remission. With improved survival, long-term sequelae—including obesity, cardiovascular disease, chronic kidney disease, neuropsychiatric impairment, obstetric complications, and reduced life expectancy—are increasingly being recognized. This review explores the evolving landscape of long-term management in immune-mediated thrombotic thrombocytopenic purpura, highlighting current challenges in surveillance, immune suppression in the second line (and beyond), and emerging opportunities for recognition of long-term sequelae.

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