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Pregnancy outcomes of patients with paroxysmal nocturnal hemoglobinuria treated with eculizumab: a Japanese experience and updated review

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Abstract

Pregnancy with paroxysmal nocturnal hemoglobinuria (PNH) is associated with significant risk of complications, such as life-threatening thrombosis. Recently, eculizumab has come into clinical use and revolutionized the treatment of PNH. However, clinical information regarding eculizumab use for PNH during pregnancy is limited. The present report describes pregnancies with PNH treated with eculizumab that were registered with the Japan PNH study group and reviews the literature. In case 1, the patient received eculizumab throughout pregnancy and delivered a healthy neonate at term, although breakthrough hemolysis occurred at 20 weeks of gestation. In case 2, the patient discontinued eculizumab before pregnancy and developed preeclampsia at 27 weeks of gestation. She received eculizumab and delivered a preterm, but healthy, neonate by cesarean section. In case 3, the patient received eculizumab from 18 weeks of gestation and delivered a healthy neonate at term without any complications. Reports of 11 pregnant women treated with eculizumab were identified in the literature. Of 14 pregnancies, including our own cases, breakthrough hemolysis and preeclampsia occurred in five and two cases, respectively. There were no thrombotic complications, maternal or neonatal deaths, or fetal structural abnormalities. Thus, eculizumab appears to be safe and effective for managing PNH during pregnancy.

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Acknowledgments

We are grateful to Alexion Pharmaceuticals for measurements of eculizumab concentration in the cord blood and breast milk. We also thank obstetricians, Dr. Takashi Ohba (Kumamoto Univ.), Dr. Munekage Yamaguchi (Kumamoto Univ.), and Dr. Hiromi Miyata (Kitano Hospital) for their clinical supports and advices.

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Authors and Affiliations

  1. Department of Pediatrics, Perinatal and Maternal Medicine, Graduate School of Tokyo Medical and Dental University (TMDU), 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan

    Naoyuki Miyasaka

  2. Department of Hematology, Graduate School of Tokyo Medical and Dental University, Tokyo, Japan

    Osamu Miura

  3. Departments of Hematology and Infectious Diseases, Kumamoto University Hospital, Kumamoto, Japan

    Tatsuya Kawaguchi

  4. Department of Hematology, Medical Research Institute Kitano Hospital, Osaka, Japan

    Nobuyoshi Arima

  5. Department of Clinical Laboratory Science, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan

    Eriko Morishita

  6. Department of Hematology, NTT Medical Center Tokyo, Tokyo, Japan

    Kensuke Usuki & Akio Urabe

  7. Division of Hematology and Rheumatology, Department of Internal Medicine, Kinki University Faculty of Medicine, Osaka-Sayama, Osaka, Japan

    Yasuyoshi Morita

  8. Department of Oncology and Haematology, Jikei University Kashiwa Hospital, Kashiwa, Chiba, Japan

    Kaichi Nishiwaki

  9. Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan

    Haruhiko Ninomiya

  10. Division of Hematology, First Department of Internal Medicine, Tokyo Medical University, Tokyo, Japan

    Akihiko Gotoh

  11. Division of Hematology, Takasago-Seibu Hospital, Takasago, Japan

    Shinsaku Imashuku

  12. Department of Cardiology and Hematology, Fukushima Medical University, Fukushima, Japan

    Tsutomu Shichishima

  13. Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Osaka, Japan

    Jun-ichi Nishimura & Yuzuru Kanakura

  14. Working Group for Pregnancy in PNH, The Japan PNH Study Group, Tokyo, Japan

    Naoyuki Miyasaka, Osamu Miura, Tatsuya Kawaguchi, Nobuyoshi Arima, Eriko Morishita, Kensuke Usuki, Yasuyoshi Morita, Kaichi Nishiwaki, Haruhiko Ninomiya, Akihiko Gotoh, Shinsaku Imashuku, Akio Urabe, Tsutomu Shichishima, Jun-ichi Nishimura & Yuzuru Kanakura

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  1. Naoyuki Miyasaka
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  2. Osamu Miura
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Correspondence to Naoyuki Miyasaka.

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Miyasaka, N., Miura, O., Kawaguchi, T. et al. Pregnancy outcomes of patients with paroxysmal nocturnal hemoglobinuria treated with eculizumab: a Japanese experience and updated review. Int J Hematol 103, 703–712 (2016). https://doi.org/10.1007/s12185-016-1946-x

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  • DOI: https://doi.org/10.1007/s12185-016-1946-x

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