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Clinical Effects of Eculizumab in PNH: Extravascular Hemolysis After Eculizumab Treatment

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Paroxysmal Nocturnal Hemoglobinuria

Abstract

The most important advance in the management of paroxysmal nocturnal hemoglobinuria (PNH) has been the introduction of eculizumab, a human monoclonal antibody against the C5 component of complement, that abrogates intravascular hemolysis by preventing the formation of the complement membrane attack complex. Complement blockade by eculizumab has proven to be clinically effective in hemolytic PNH, reducing the transfusion requirement in most of patients. However, in almost all PNH patients on eculizumab, a proportion of PNH red cells become coated with C3 and thus a potential target of phagocytosis by macrophages. This phagocytosis results in a variable degree of extravascular hemolysis that in some patients may limit the clinical benefit from eculizumab: in fact, at least one in four of transfusion-dependent PNH patients remain transfusion dependent even on eculizumab, and these patients may also have a high risk to develop iron overload. Unfortunately, there are not yet established treatments for the cases in which this extravascular hemolysis became clinically relevant: it is possible that new strategies for complement blockade could overcome this condition.

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Acknowledgments

PNH studies has been in part funded by the Associazione Italiana Emoglobinuria Parossistica Notturna (RN) and the Aplastic Anemia & MDS

International Foundation (RN and AMR).

We thank all the colleagues within and outside our national PNH network for sharing their experience and their thoughts.

Finally we are particularly grateful to all of our patients and their families.

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Authors and Affiliations

  1. Core Research Laboratory, Istituto Toscano Tumori, Viale Pieraccini 6, 50139, Florence, Italy

    Rosario Notaro

  2. Hematology, Department of Clinical Medicine and Surgery, Federico II University of Naples, Via Pansini 5, 80131, Naples, Italy

    Antonio M. Risitano M.D., Ph.D.

Authors
  1. Rosario Notaro
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  2. Antonio M. Risitano M.D., Ph.D.
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Correspondence to Rosario Notaro .

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Editors and Affiliations

  1. Department of Hematology and Ocology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan

    Yuzuru Kanakura

  2. Immunology Frontier Research Center, Osaka University, Suita, Osaka, Japan

    Taroh Kinoshita

  3. Dept of Hematology and Ocology, Osaka University Dept of Hematology and Ocology, Suita, Osaka, Japan

    Jun-ichi Nishimura

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Notaro, R., Risitano, A.M. (2017). Clinical Effects of Eculizumab in PNH: Extravascular Hemolysis After Eculizumab Treatment. In: Kanakura, Y., Kinoshita, T., Nishimura, Ji. (eds) Paroxysmal Nocturnal Hemoglobinuria. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56003-6_17

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  • DOI: https://doi.org/10.1007/978-4-431-56003-6_17

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  • Publisher Name: Springer, Tokyo

  • Print ISBN: 978-4-431-56001-2

  • Online ISBN: 978-4-431-56003-6

  • eBook Packages: MedicineMedicine (R0)

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