Precision medicine in thrombotic thrombocytopenic purpura: a narrative review.

Abstract

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic microangiopathy driven by severe ADAMTS13 deficiency with consequent ultra-large von Willebrand factor-mediated microthrombosis. Over the last two decades, understanding of the ADAMTS13-vWF axis has transformed management and made TTP a model for precision medicine. This narrative review (adult focus) synthesizes contemporary evidence on diagnosis, treatment, genetics, and emerging therapies in immune-mediated TTP. We summarize a pragmatic, biomarker-guided algorithm integrating early therapeutic plasma exchange and corticosteroids, upfront rituximab to suppress anti-ADAMTS13 autoimmunity, and caplacizumab to block vWF-platelet interactions; define escalation strategies for refractory disease (e.g., proteasome inhibition); and formalize treat-to-target de-escalation anchored to ADAMTS13 recovery. We emphasize the role of rapid ADAMTS13 assays for front-door triage, routine ADAMTS13 monitoring in remission, and preemptive rituximab at biochemical relapse to avert clinical recurrence. Precision diagnostics are extended by genetic markers (e.g., HLA associations) and emerging biomarkers that may refine relapse risk. Finally, we discuss near-term opportunities-point-of-care ADAMTS13 assays, longer-acting vWF-pathway inhibitors, and data-driven risk tools-that can further individualize timing and intensity of therapy. Collectively, a biomarker-first strategy offers a clear path to fewer exacerbations, fewer relapses, and more consistent outcomes.