[Treatment of immune-mediated thrombotic thrombocytopenic purpura: A decisive turning point]

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare and life-threatening thrombotic microangiopathy characterized by severe deficiency of ADAMTS13, the enzyme that cleaves von Willebrand factor multimers. Recent insights into iTTP pathophysiology have led to the development of new therapies targeting ADAMTS13 replacement, anti-ADAMTS13 antibodies, and von Willebrand factor-platelet interactions. New maximalist therapeutic strategies are emerging based on triple therapy. While plasma exchange remains the cornerstone therapy of the acute phase, the introduction of front-line immunosuppressive treatments, corticosteroids and rituximab, has led to a reduction in exacerbations and relapses but without any significant improvement in survival. Caplacizumab, a bivalent humanized anti-von Willebrand factor nanobody, is poised to revolutionize the treatment of the acute phase. By inhibiting the interaction between von Willebrand factor multimers and platelets, caplacizumab prevents platelets adhesion, prevents the formation of new microthrombi and protects organs from ischemia. Its early combination with plasma exchange and immunosuppressive therapy prevents unfavorable outcomes and reduces the burden of care. Supported by repeated ADAMTS13 assays, rituximab prevents relapse in patients with persistent or recurrent ADAMTS13 deficiency in clinical remission. This review examines how advances in diagnostics and targeted therapies are changing the current treatment paradigm in both the acute and remission phases and are contributing to dramatically improve the iTTP prognosis.