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Effect of eculizumab and recombinant human soluble thrombomodulin combination therapy in a 7-year-old girl with atypical hemolytic uremic syndrome due to anti-factor H autoantibodies

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Abstract

Atypical hemolytic uremic syndrome (aHUS), which is defined as non-Shiga toxin-associated hemolytic uremic syndrome, is a type of thrombotic microangiopathy. This syndrome presents with hemolytic anemia, thrombocytopenia, and acute kidney injury. Excessive complement activation due to genetic disorders of the complement system or production of autoantibodies to factor H (FH) causes the disease. We report a successful treatment course using eculizumab and recombinant human soluble thrombomodulin (rTMD) for a 7-year-old girl with aHUS due to anti-FH autoantibodies. Although her chief complaints were abdominal pain and loose stools, we were finally able to diagnose her with aHUS because Shiga toxin-producing Escherichia coli was not detected in her feces and a hemolytic assay analyzing FH function was positive. We administrated rTMD to our patient because of signs of disseminated intravascular coagulation. Soon after the therapeutic intervention, the platelet count began to increase and abdominal pain was moderately improved. Plasma exchange limited the efficacy of her disease. Therefore, we administered eculizumab, monoclonal humanized antibody against C5, 3 weeks after admission. Platelet counts immediately increased and kidney function gradually recovered. Genetic disorders were not detected. However, anti-FH autoantibody was observed. There were no symptoms for recurrence of aHUS or kidney dysfunction for 15 months, as a result of the administration of eculizumab every other week. In conclusion, combination therapy of eculizumab and rTMD was effective for an aHUS patient. This therapy may be helpful for improving the prognosis and long-term kidney function of aHUS patients.

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Acknowledgments

The authors acknowledge Camille Bedrosian, MD, Senior Vice President and Chief Medical Officer of Alexion Pharmaceuticals, Inc., for her important recommendation on the treatment of aHUS. We appreciate Dr. Yoshihiro Fujimura and Ms. Yoko Yoshida, Department of Blood Transfusion, Nara Medical University, Japan, for their contribution to the analysis of ADAMTS13 and FH function. We also thank Dr. Yoshihiko Hidaka, Department of Pediatrics, Shinshu University School of Medicine, Matsumoto, Japan, and Dr. Nobuaki Takagi, Department of Pediatrics, Hyogo College of Medicine, Hyogo, Japan, for their essential advice and assistance on the diagnosis of our patient.

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Authors and Affiliations

  1. Department of Pediatrics and Developmental Biology, Graduate School of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, 113-8519, Japan

    Tomohiro Udagawa, Yaeko Motoyoshi, Yu Matsumura, Akira Takei, Shohei Ariji, Masayuki Nagasawa, Tomohiro Morio & Shuki Mizutani

  2. Department of Clinical Pathology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan

    Eisaku Ito

  3. Department of Nephrology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan

    Motoko Chiga

Authors
  1. Tomohiro Udagawa
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  2. Yaeko Motoyoshi
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  3. Yu Matsumura
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  4. Akira Takei
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  5. Shohei Ariji
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  6. Eisaku Ito
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  7. Motoko Chiga
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  8. Masayuki Nagasawa
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  9. Tomohiro Morio
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  10. Shuki Mizutani
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Corresponding author

Correspondence to Tomohiro Udagawa.

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Udagawa, T., Motoyoshi, Y., Matsumura, Y. et al. Effect of eculizumab and recombinant human soluble thrombomodulin combination therapy in a 7-year-old girl with atypical hemolytic uremic syndrome due to anti-factor H autoantibodies. CEN Case Rep 3, 110–117 (2014). https://doi.org/10.1007/s13730-013-0097-7

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  • DOI: https://doi.org/10.1007/s13730-013-0097-7

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