Immune thrombotic thrombocytopenic purpura: a story still unfolding

Background Immune thrombotic thrombocytopenic purpura (iTTP) is a subtype of TTP that results from acquired severe A Disintegrin and Metalloproteinase with ThromboSpondin type 1 motif, member 13 (ADAMTS13) enzyme deficiency. It is a rare but life-threatening disorder caused by autoantibodies to ADAMTS13. This leads to uncontrolled platelet aggregation in small vessels, resulting in microangiopathic hemolytic anemia with variable organ ischemia. Objective This study integrates current developments in epidemiology, pathogenesis, diagnosis, prognosis, and treatment of iTTP, focusing on ongoing challenges and research directions. Patients and methods A peer-reviewed literature was conducted through PubMed, Scopus, and Web of Science. Search terms were ‘iTTP’ ‘ADAMTS13,’ ‘plasma exchange,’ ‘caplacizumab,’ ‘rituximab’ with their respective synonyms. The major articles’ reference lists were also screened for additional sources. Results Ittp has a global incidence estimated at between 1.81 and 3.93 cases per million person-years, with notable regional variations. It disproportionately affects females and specific ethnic populations. Diagnosis relies on ADAMTS13 activity assays, though the PLASMIC score offers a practical alternative when immediate testing is unavailable. Acute management typically involves therapeutic plasma exchange, immunosuppressive therapy, and caplacizumab, contributing to survival rates exceeding 95%. Persistent ADAMTS13 deficiency during remission is a key predictor of relapse. Long-term complications include thromboembolic events and cognitive impairment. Emerging therapies such as recombinant ADAMTS13 and proteasome inhibitors are under investigation, while biomarker-driven monitoring paves the way for more personalized treatment strategies. Conclusions Advances in diagnosing and treating iTTP have led to better survival and fewer relapses. Still many patients face ongoing health challenges and risk of relapse, showing the need for personalized care, better biomarker validation, and more effective treatments. Looking ahead to unify global standards for diagnosis and treatment and using precision medicine to improve patient outcomes further.