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Early eradication of factor VIII inhibitor in patients with congenital hemophilia A by immune tolerance induction with a high dose of immunoglobulin

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Abstract

The production of factor VIII (FVIII) inhibitory antibodies is a serious problem in patients with hemophilia A. Immune tolerance induction (ITI) is the only strategy proven to eradicate persistent inhibitors and has been shown to be successful in 70 % of patients with hemophilia A. However, a minority of hemophilia patients present life-long inhibitors. To eliminate such inhibitors, we designed an intravenous immunoglobulin (IVIG) strategy in combination with high dose recombinant FVIII for ITI in hemophilia A children with inhibitors. Four previously untreated patients produced inhibitors within 16 exposures to FVIII. The peak inhibitor titers in these patients ranged from 3 to 14 BU/mL. The patients received ITI combined with IVIG within 1.5 months after the inhibitors were detected. All patients showed a negative titer for inhibitors by 28 days, with no anamnestic responses. The recovery of FVIII in the plasma concentration was normalized within three months after initiation of ITI. An additional course of IVIG administration led to induction of complete tolerance by 20 months after initiation of ITI therapy in all patients. ITI treatment with high-dose FVIII combined with IVIG may be effective for the early elimination of inhibitors.

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Acknowledgments

We thank Professor Emeritus Akira Yoshioka from the Nara Prefectural Medical University, Nara, Japan, for his helpful comments in completing this study.

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Authors and Affiliations

  1. Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Yoko Mizoguchi, Aya Furue, Reiko Kagawa, Ikue Chijimatsu, Keita Tomioka, Maiko Shimomura, Yusuke Imanaka, Shiho Nishimura, Satoshi Saito, Mizuka Miki, Hiroshi Kawaguchi & Masao Kobayashi

  2. Department of Pediatrics, Miyoshi Central Hospital, Miyoshi, Japan

    Atsushi Ono

  3. Department of Pediatrics, Chugoku Rousai Hospital, Kure, Japan

    Nakao Konishi

Authors
  1. Yoko Mizoguchi
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  2. Aya Furue
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  3. Reiko Kagawa
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  4. Ikue Chijimatsu
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  5. Keita Tomioka
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  6. Maiko Shimomura
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  7. Yusuke Imanaka
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  8. Shiho Nishimura
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  9. Satoshi Saito
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  10. Mizuka Miki
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  11. Atsushi Ono
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  12. Nakao Konishi
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  13. Hiroshi Kawaguchi
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  14. Masao Kobayashi
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Corresponding author

Correspondence to Masao Kobayashi.

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The authors declare no conflict of interest.

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Mizoguchi, Y., Furue, A., Kagawa, R. et al. Early eradication of factor VIII inhibitor in patients with congenital hemophilia A by immune tolerance induction with a high dose of immunoglobulin. Int J Hematol 103, 473–477 (2016). https://doi.org/10.1007/s12185-016-1943-0

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  • DOI: https://doi.org/10.1007/s12185-016-1943-0

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