International Journal of Hematology

, Volume 107, Issue 1, pp 112–116 | Cite as

First report of real-time monitoring of coagulation function potential and IgG subtype of anti-FVIII autoantibodies in a child with acquired hemophilia A associated with streptococcal infection and amoxicillin

  • Masahiro Takeyama
  • Keiji Nogami
  • Takahiro Kajimoto
  • Kenichi Ogiwara
  • Tomoko Matsumoto
  • Midori Shima
Case Report


We describe an 8-year-old boy with acquired hemophilia A (AHA) associated with streptococcal infection and amoxicillin. Laboratory data revealed low factor VIII activity (FVIII:C, 1.5 IU/dl), and FVIII inhibitor (15.9 BU/ml). Comprehensive coagulation function assays, including rotation thromboelastometry (ROTEM®), revealed a markedly prolonged clotting time. Thrombin and plasmin generation (TG/PG) appeared to be moderately impaired. The inhibitor epitope of his anti-FVIII autoantibody recognized light and heavy chains. He was treated with Novoseven® and prednisolone, resulting in rapid improvement. ROTEM showed the return of coagulation time to normal level on day 20, and TG gradually improved. PG was moderately reduced in the clinical early phase, but improved at day 20. The patient’s IgG subtype was IgG4 at onset. IgG1 was transiently positive on day 20, but negative on day 46. FVIII inhibitor gradually decreased and was completely absent after day 46, along with the elevated FVIII:C. IgG4 was again elevated on day 83, followed by a rapid decrease, indicative of the presence of non-neutralizing antibody, which remains currently undetected. We for the first time report changes in comprehensive coagulation function and IgG subtype of anti-FVIII antibody in a rare pediatric case of AHA.


Acquired hemophila A Children Factor VIII Inhibitor IgG Streptococcal infection 



We would like to thank Dr. Koji Yada and Dr. Yasuaki Shida for clinical support, and Ms. Arisa Takenaka for special assistance with the T/P-G assays.

Author contributions

Dr. Takeyama designed the research, acquired and analyzed the data, and drafted the initial manuscript; Dr. Nogami interpreted the data, revised the manuscript, and approved the final version to be published; Dr. Kajimoto provided clinical support; Dr. Ogiwara and Dr. Matsumoto acquired and analyzed the data; Dr. Shima oversaw the manuscript creation and critically reviewed the manuscript; and all authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work. There are no prior publications or submissions with any overlapping information, including studies and patients. Our manuscript has not been and will not be submitted to any other journal while it is under consideration by International Journal of Hematology.

Compliance with ethical standards

Funding source

This work was partly supported by Grant-in-Aids for Scientific Research (KAKENHI) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) to M. Takeyama (Grant No. 26461592) and K. Nogami (Grant No. 15K09663).

Financial disclosure

M. Takeyama and K. Ogiwara have received funding for their research from Novo Nordisk and Kaketsuken. K. Nogami has received funding for his research from Novo Nordisk, Bayer, Baxalta, Biogen, Chugai, and Kaketsuken. T. Matsumoto belongs to a course endowed by Baxalta Japan Co. Ltd. T. Kajimoto has no financial disclosure. M. Shima has received funding for his research from Novo Nordisk, Bayer, Baxalta, Pfizer, Biogen, Novo Nordisk, Chugai, and Kaketsuken.

Conflict of interest

M. Takeyama, K. Nogami, K. Ogiwara, and M. Shima have received research funding from Novo Nordisk. T. Matsumoto teaches a course endowed by Baxalta Japan Co. Ltd. T. Kajimoto has no conflict of interest to disclose.


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Copyright information

© The Japanese Society of Hematology 2017

Authors and Affiliations

  • Masahiro Takeyama
    • 1
  • Keiji Nogami
    • 1
  • Takahiro Kajimoto
    • 1
  • Kenichi Ogiwara
    • 1
  • Tomoko Matsumoto
    • 2
  • Midori Shima
    • 1
  1. 1.Department of PediatricsNara Medical UniversityKashiharaJapan
  2. 2.Course of Hemophilia Treatment and PathologyNara Medical UniversityKashiharaJapan

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