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    Oral Communication

    Platelet Disorders, von Willebrand Disease and Thrombotic Microangiopathies

    Immune-Mediated Thrombocytopenic Disorders

    OC 42.3 - Immune-mediated TTP patients in remission with recovered ADAMTS13 activity but an open ADAMTS13 conformation are at risk for earlier ADAMTS13 relapse

    Monday, June 26, 2023
    15:15 – 15:30 ET
    Room: 710A
    Session Available As: On-Demand

      Co-Author(s)

    • LD

      Laure De Waele

      Dr
      Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk
      Kortrijk, West-Vlaanderen, Belgium

      • Presenting Author(s)

    • Kazuya SAKAI, MD, PhD

      Dr.
      Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk
      8500, West-Vlaanderen, Belgium

      • Co-Author(s)

    • IM

      Ilaria Mancini, PhD

      Post-Doc Research Fellow
      Università degli Studi di Milano, Department of Pathophysiology and Transplantation and Fondazione Luigi Villa, Milan, Italy
      Milan, Lombardia, Italy

    • GS

      György Sinkovits

      Dr
      Department of Internal Medicine and Hematology, Semmelweis University and Research Group for Immunology and Haematology, Semmelweis University - Eötvös Loránd Research Network (Office for Supported Research Groups), Budapest
      Budapest, Budapest, Hungary

    • TF

      Tanja Falter

      Dr.
      Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg University Mainz
      Mainz, Rheinland-Pfalz, Germany

    • TI

      Takashi Inoue

      Dr, MPH
      Department of Evidence-Based Medicine, Nara Medical University, , Kashihara
      Kashihara, Nara, Japan

    • Pasquale Agosti, MD, PhD

      Università degli Studi di Milano, Department of Pathophysiology and Transplantation and Fondazione Luigi Villa, Milan, Italy
      Milano, Lombardia, Italy

    • HR

      Heidi Rossmann

      Dr
      Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center of the Johannes Gutenberg University, Mainz
      Mainz, Rheinland-Pfalz, Germany

    • CV

      Charis Von Auer

      Dr
      Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University, Mainz
      Mainz, Rheinland-Pfalz, Germany

    • CT

      Claudia Tersteeg

      Prof., Dr.
      Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium
      Kortrijk, West-Vlaanderen, Belgium

    • SD

      Simon F. De Meyer

      Prof., Dr., Eng.
      Laboratory for Thrombosis Research, KU Leuven Campus Kulak Kortrijk, Kortrijk, Belgium
      Kortrijk, West-Vlaanderen, Belgium

    • BJ

      Bérangère S Joly

      Professor
      Service d’Hématologie Biologique, Hôpital Lariboisière, Assistance Publique–Hôpitaux de Paris and EA3518, Institut de Recherche Saint Louis, Université de Paris, Paris
      Paris, Ile-de-France, France

    • AV

      Agnès Veyradier

      Professor
      Service d’Hématologie Biologique, Hôpital Lariboisière, Assistance Publique–Hôpitaux de Paris and EA3518, Institut de Recherche Saint Louis, Université de Paris, Paris
      Paris, Ile-de-France, France

    • Paul Coppo, MD, PhD (he/him/his)

      Professor
      National Reference Center for Thrombotic Microangiopathy, Hôpital Saint-Antoine, Assistance Publique-Hôpitaux de Paris and Sorbonne – Université (AP-HP.6), Paris, France
      Paris, Ile-de-France, France

    • RF

      Rob Fijnheer

      Professor
      Department for Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht University, Utrecht
      Utrecht, Utrecht, Netherlands

    • Flora Peyvandi, MD, PhD (she/her/hers)

      Director
      IRCCS Ca' Granda Maggiore Hospital Foundation, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milano, Italy; Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milano, Italy
      Milano, Lombardia, Italy

    • ZP

      Zoltan Prohászka

      Professor
      Department of Internal Medicine and Hematology, Semmelweis University and Research Group for Immunology and Haematology, Semmelweis University - Eötvös Loránd Research Network (Office for Supported Research Groups), Budapest
      Budapest, Budapest, Hungary

    • BL

      Bernhard Lämmle

      Professor
      Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg University, Mainz
      Mainz, Rheinland-Pfalz, Germany

    • Karen Vanhoorelbeke, PhD

      Prof., Dr.
      KU Leuven
      Kortrijk, West-Vlaanderen, Belgium

    Background: ADAMTS13 in patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP) adopts an open conformation in the acute phase while being closed in healthy donors. However, 38% of iTTP patients in remission with normalized ADAMTS13 activity (>50%) still had open ADAMTS13.

    Aims: To investigate whether open ADAMTS13, i,e, a conformation index > 0.5, can serve as a novel biomarker to predict ADAMTS13 relapse and/or clinical relapse in iTTP.

    Methods: Clinical follow-up data were collected for 84 remission samples with ADAMTS13 activity >50% (retained from 82 iTTP patients). First, open or closed ADAMTS13 conformation was dichotomized based on the 0.5 conformation index normality cut-off. Cumulative rates and relative risks of ADAMTS13 or clinical relapse for open versus closed ADAMTS13 were analyzed by Kaplan-Meier analysis and Cox regression. Next, classification and regression tree (CART) analysis was used to investigate which conformation index cut-off value optimally predicts ADAMTS13 relapse. Multivariable Cox regression, sensitivity and restriction analyses were performed to evaluate possible confounders and effect modifiers.

    Results: Open ADAMTS13 (conformation index >0.5) showed a trend towards prediction of ADAMTS13 relapse (HR 2.37, 95% CI 0.93-6.01, p = 0.054). Next, conformation index >0.645 was identified as the optimal cut-off for ADAMTS13 relapse prediction (HR 3.38, 95% CI (1.25-9.11), p=0.005). Open ADAMTS13 showed a similar trend predicting earlier clinical relapse (HR 2.25) although with a larger uncertainty around the estimate (95% CI (0.64-7.98), p=0.19). Conformation index >0.835 showed an optimal cut-off for clinical relapse prediction (HR 4.49, 95% CI 0.90-22.38, p=0.009). These findings were not confounded or modified by earlier rituximab administration, pre-emptive interventions, ADAMTS13 antigen, activity or anti-ADAMTS13 autoantibody levels.

    Conclusion(s): Detection of open ADAMTS13, especially with a conformation index >0.645, can be a warning to intensify ADAMTS13 activity monitoring so as to timely notice ADAMTS13 relapse and prevent clinical relapse.

    Learning Objectives:

    • Upon completion, participant will be able to recognize that open ADAMTS13 is a novel biomarker in acute iTTP.
    • Upon completion, participant will be able to understand that open ADAMTS13 is also a promising marker to predict early ADAMTS13 relapse during remission.
    • Upon completion, participant will be able to list any other risk factors predicting ADAMTS13/clinical relapse.