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ADAMTS13-specific circulating immune complexes as potential predictors of relapse in patients with acquired thrombotic thrombocytopenic purpura

  • Author Footnotes
    1 These authors contributed equally to this work.
    Ilaria Mancini
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Pathophysiology and Transplantation, Università degli Studi di Milano, and Fondazione Luigi Villa, Milan, Italy
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Barbara Ferrari
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and Fondazione Luigi Villa, Milan, Italy
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  • Carla Valsecchi
    Affiliations
    Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and Fondazione Luigi Villa, Milan, Italy
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  • Silvia Pontiggia
    Affiliations
    Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and Fondazione Luigi Villa, Milan, Italy
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  • Marco Fornili
    Affiliations
    Unit of Medical Statistics, Biometry and Bioinformatics “Giulio A. Maccacaro”, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
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  • Elia Biganzoli
    Affiliations
    Unit of Medical Statistics, Biometry and Bioinformatics “Giulio A. Maccacaro”, Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
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  • Flora Peyvandi
    Correspondence
    Corresponding author at: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Milano, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Via Pace 9, 20122 Milan, Italy.
    Affiliations
    Department of Pathophysiology and Transplantation, Università degli Studi di Milano, and Fondazione Luigi Villa, Milan, Italy

    Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and Fondazione Luigi Villa, Milan, Italy
    Search for articles by this author
  • on behalf ofItalian Group of TTP Investigators
  • Author Footnotes
    1 These authors contributed equally to this work.
Published:November 22, 2016DOI:https://doi.org/10.1016/j.ejim.2016.11.003

      Highlights

      • Clinical value of ADAMTS13-specific circulating immune complexes (CICs) was assessed.
      • CICs level at the first TTP event did not reflect the severity of the acute episode.
      • CICs seemed to confer an increased relapse risk within 2 years from first TTP event.
      • CICs measurement may help to predict TTP recurrence in high-risk patients.

      Abstract

      Background

      Acquired thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy due to the development of autoantibodies against the VWF-cleaving protease ADAMTS13. ADAMTS13-specific circulating immune complexes (CICs) have been described in patients with acquired TTP, but their clinical relevance remained to be established. The aim of this study was to assess the association between ADAMTS13-specific CICs and ADAMTS13-related measurements, clinical and laboratory markers of disease severity, and occurrence of TTP relapse, in autoimmune TTP patients.

      Material and methods

      We measured ADAMTS13-specific CICs in 51 patients with severe ADAMTS13 deficiency and anti-ADAMTS13 autoantibodies, at the first episode of acquired TTP. The associations between ADAMTS13-specific CICs and the variables of interest were assessed by linear, logistic and Cox proportional hazard regression models, where appropriate.

      Results

      The prevalence of ADAMTS13-specific CICs in patients experiencing the first TTP episode was 39% (95% confidence intervals [CI]: 26–52%). ADAMTS13-specific CICs were not associated neither with laboratory markers of disease severity, nor with patterns of clinical presentation. Conversely, among 45 survivors, a positive association was found between the presence of ADAMTS13-specific CICs and the risk of recurrence within 2 years after the first TTP episode (adjusted hazard ratio, 3.4 [95% CI: 0.9 to 13.5]).

      Conclusions

      ADAMTS13-specific CICs seem to be able to predict the recurrence of acute TTP episodes in the first 2 years after disease onset. Therefore, their measurement might be used as a tool to stratify the risk of disease relapse, with potential influence on surveillance and therapeutic choices during remission phase.

      Keywords

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