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Thrombophilia in PNH

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Paroxysmal Nocturnal Hemoglobinuria

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Abstract

Thromboembolic event is the most important complication of paroxysmal nocturnal hemoglobinuria (PNH) affecting its mortality. The pathophysiological mechanisms underlying thrombosis in PNH have not been fully clarified; multiple factors are likely to be involved. They are likely to be related to the complement activation on/around red blood cells (RBC), white blood cells, and particularly platelets. Intravascular hemolysis also contributes to the mechanisms through the release of free hemoglobin, depletion of nitric oxide (NO), and generation of RBC-derived microparticles (MP). Elevated MP in the plasma which derive from platelets, endothelial cells, and RBC, in total, enhance the prothrombotic states in the circulation. Recent researches have revealed close interactions between coagulation and complement systems, enhancing each other. Continuous activation of complement makes a vicious loop enhancing the coagulation/complement systems interacting with blood cells and endothelial cells in PNH.

Furthermore, the key role of complement activation in the development of thrombosis has been shown also by the effectiveness of eculizumab (humanized monoclonal antihuman C5 antibody) in the prevention of thromboembolic events in PNH. Because thrombotic complications impact mortality and eculizumab exerts a dramatic effect, commencement of eculizumab is recommended for patients with PNH who have had thromboembolic episodes. If eculizumab is not available or is ineffective, prophylactic anticoagulation is required in those with larger proportion of PNH white cells. It should be noted that cases with smaller proportions of PNH cells also have a higher risk of thrombosis than normal individuals.

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Acknowledgment

We thank Dr. Shinya Katsutani, Hiroshima University Hospital, for his provision of a CT of splenic vein thrombosis in a patient with PNH. We also thank Dr. Yukinori Kozuma, University of Tsukuba, for his cooperation with HN at flow cytometric analysis of complement-mediated activation of platelets in PNH.

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Authors and Affiliations

  1. Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan

    Haruhiko Ninomiya M.D., Ph.D.

  2. Department of Haematology, St. James’ University Hospital, Beckett Street, Leeds, West Yorkshire, LS9 7TF, UK

    Anita Hill MBChB (Hons), Ph.D.

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  1. Haruhiko Ninomiya M.D., Ph.D.
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  2. Anita Hill MBChB (Hons), Ph.D.
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Correspondence to Haruhiko Ninomiya M.D., Ph.D. .

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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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Ninomiya, H., Hill, A. (2017). Thrombophilia in PNH. In: Kanakura, Y., Kinoshita, T., Nishimura, Ji. (eds) Paroxysmal Nocturnal Hemoglobinuria. Springer, Tokyo. https://doi.org/10.1007/978-4-431-56003-6_9

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