AUTHOR=Escribano-Serrat Silvia , Salas María Queralt , Pascual-Izquierdo Cristina , Fernández Villalobos Manuel , Gómez-Seguí Inés , Fidalgo Teresa , Fernández Docampo Marta , Martínez Nieto Jorge , Lamas Óscar , Lozano Miquel , Cid Joan , Charry Paola , Pino Marc , Molina Patricia , De Moner Blanca , Ramos Álex , Moreno-Castaño Ana Belén , Martinez-Sanchez Julia , Escolar Ginés , Díaz-Ricart Maribel 

TITLE=EASIX, a new tool to predict response and refractoriness in immune-mediated thrombotic thrombocytopenic purpura

JOURNAL=Frontiers in Immunology

VOLUME=Volume 16 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1700907

DOI=10.3389/fimmu.2025.1700907

ISSN=1664-3224

ABSTRACT=IntroductionImmune-mediated thrombotic thrombocytopenic purpura (iTTP) is a life-threatening thrombotic microangiopathy resulting from severe ADAMTS13 deficiency. Caplacizumab accelerates platelet recovery, but ~15% of patients remain refractory, and endothelial/microvascular injury or low ADAMTS13 activity may persist despite remission, highlighting the need for biomarkers. We evaluated the Endothelial Activation and Stress Index (EASIX), an endothelial dysfunction surrogate, dynamics and ability to predict refractoriness and mortality in iTTP.MethodsFifty-five adults receiving ≥2 therapies (corticosteroids, plasma exchange, rituximab, and/or caplacizumab) were studied. Clinical and laboratory data were collected at baseline, days 1–2, 7, 14, 21, 28, 35, and at treatment discontinuation, including clinical or ADAMTS13 relapses. EASIX was calculated at each time point; logistic regression and ROC analyses evaluated its predictive performance for refractoriness and mortality. ResultsMedian age was 47 years; 13% were refractory, and 7% died. In responders, EASIX dropped below 1 by day 7, earlier than ADAMTS13 recovery (day 21). Clinical relapses showed EASIX spikes (median 13.2), unlike ADAMTS13-only relapses. Baseline EASIX was higher in refractory patients (752 vs. 91; p=0.007), remaining elevated at days 7 and 14. Higher pre-treatment EASIX predicted refractoriness (OR = 1.003; p=0.021; AUC = 0.811; sensitivity 100%; specificity 58.7%) and mortality (OR = 1.004; p=0.027). DiscussionEASIX may help predict refractoriness and death, improving monitoring in iTTP.