EASIX, A NEW TOOL TO PREDICT RESPONSE AND REFRACTORINESS IN IMMUNE-MEDIATED THROMBOTIC THROMBOCYTOPENIC PURPURA

Silvia Escribano Serrat^1,2*María Queralt Salas³Crisitina Pascual-Izquierdo⁴Manuel Jorge Fernández Villalobos⁴Inés Gómez⁵Teresa Fidalgo⁶Marta Fernández Docampo⁷Jorge Martínez Nieto⁸Óscar Lamas⁵Miquel Lozano⁹Joan Cid⁹Paola Charry⁹Marc Pino¹Patricia Molina¹Blanca De Moner Rafel^1,10,2Álex Ramos^1,2Ana Belen Moreno-Castaño¹Julia Martinez-Sanchez^1,2Gines Escolar^1,2Maribel Diaz-Ricart^1,2

• ¹Laboratory of Hemostasis and Erythropathology, Hematopathology, Pathology Department, CDB, Hospital Clínic de Barcelona, Barcelona, Spain
• ²Instituto de Investigaciones Biomédicas August Pi i Sunyer (IDIBAPS), Barcelona, Spain
• ³Hematopoietic Transplantation Unit, Hospital Clínic de Barcelona, ICAMS, Barcelona, Spain
• ⁴Hematology Department, Hospital Universitario Gregorio Marañón, Instituto de Investigación Gregorio Marañón, Madrid, Spain
• ⁵Hematology Department, Hospital Universitario La Fe, Valencia, Spain
• ⁶Centro Hospitalar Universitário de Coimbra, Coimbra, Portugal
• ⁷Área de Gestión Integrada de A Coruña. Instituto de investigación Biomédica de A Coruña (INIBIC), Coruña, Spain
• ⁸Hospital Clinico San Carlos, Madrid, Spain
• ⁹Apheresis & Cellular Therapy Unit, Department of Hemotherapy and Hemostasis, ICAMS, Hospital Clínic de Barcelona, Barcelona, Spain
• ¹⁰Josep Carreras Leukaemia Research Institute, Hospital Clínic de Barcelona, Barcelona, Spain

Immune-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. Fifty-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. Median 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). EASIX may help predict refractoriness and death, improving monitoring in iTTP.