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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• 作者：Yoko Mizoguchi ; Aya Furue ; Reiko Kagawa…
• 关键词：Hemophilia ; Inhibitors ; ITI ; IVIG
• 刊名：International Journal of Hematology
• 出版年：2016
• 出版时间：April 2016
• 年：2016
• 卷：103
• 期：4
• 页码：473-477
• 全文大小：475 KB
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• 作者单位：Yoko Mizoguchi (1)
  Aya Furue (1)
  Reiko Kagawa (1)
  Ikue Chijimatsu (1)
  Keita Tomioka (1)
  Maiko Shimomura (1)
  Yusuke Imanaka (1)
  Shiho Nishimura (1)
  Satoshi Saito (1)
  Mizuka Miki (1)
  Atsushi Ono (2)
  Nakao Konishi (3)
  Hiroshi Kawaguchi (1)
  Masao Kobayashi (1)
  
  1. Department of Pediatrics, Hiroshima University Graduate School of Biomedical and Health Sciences, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan
  2. Department of Pediatrics, Miyoshi Central Hospital, Miyoshi, Japan
  3. Department of Pediatrics, Chugoku Rousai Hospital, Kure, Japan
  
• 刊物主题：Hematology; Oncology;
• 出版者：Springer Japan
• ISSN：1865-3774

文摘

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.