TY - JOUR
T1 - Acquired Hemophilia A Associated with Dipeptidyl Peptidase-4 Inhibitors for the Treatment of Type 2 Diabetes Mellitus
T2 - A Single-Center Case Series in Japan
AU - Yamasaki, Satoshi
AU - Kadowaki, Masanori
AU - Jiromaru, Takashi
AU - Takase, Ken
AU - Iwasaki, Hiromi
N1 - Funding Information:
We thank the patients and clinical staff for their participation in the study. No funding or sponsorship was received for this study or publication of this article. The article processing charges were funded by the authors. The authors acknowledge The Clinical Research Institute, Kyushu Medical Hospital for editorial support. The authors also thank Dr. Owen Proudfoot from Edanz Group (http://www.edanzediting.com/ac) for editing a draft of this manuscript. Editorial assistance was funded by the authors. All named authors meet the International Committee of Medical Journal Editors criteria for authorship of this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published. Satoshi Yamasaki designed the study, analyzed the data, and prepared the manuscript. Masanori Kadowaki, Takashi Jiromaru, Ken Takase, and Hiromi Iwasaki prepared and reviewed the manuscript. All authors have approved the final manuscript. Satoshi Yamasaki, Masanori Kadowaki, Takashi Jiromaru, Ken Takase and Hiromi Iwasaki have nothing to disclose. The present case series was retrospective and did not involve any experimental intervention. Accordingly, no institutional ethical approval was required or sought. Informed consent was obtained from all individual participants included in the study. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/6/1
Y1 - 2019/6/1
N2 - Herein we describe four patients with acquired hemophilia A (AHA) caused by factor VIII (FVIII) inhibitor and histories of dipeptidyl peptidase-4 inhibitor (DPP4-I) treatment for diabetes mellitus (DM). Drug exposure can cause a breakdown of immune tolerance to FVIII associated with CD4 T cells, resulting in the induction of autoantibodies against FVIII. In patient 1 in the present series, FVIII inhibitor disappeared after DPP4-I treatment. The DPP4-I treatment was stopped faster in patient 1 than it was in patient 2, whose FVIII inhibitor titer was higher than patient 1’s. Two patients died: patient 3 due to brain infarction after recurrence associated with the development of sigmoid colon rupture, and patient 4 due to multiple organ failure associated with Clostridium difficile colitis. DPP4-I treatment may create an ideal environment for the induction of new antibodies and AHA onset associated with tumor necrosis factor-α reduction. These are the first reported cases of the potential development and/or prolonging of AHA after DDP4-I treatment for DM, and they suggest possible disease associations.
AB - Herein we describe four patients with acquired hemophilia A (AHA) caused by factor VIII (FVIII) inhibitor and histories of dipeptidyl peptidase-4 inhibitor (DPP4-I) treatment for diabetes mellitus (DM). Drug exposure can cause a breakdown of immune tolerance to FVIII associated with CD4 T cells, resulting in the induction of autoantibodies against FVIII. In patient 1 in the present series, FVIII inhibitor disappeared after DPP4-I treatment. The DPP4-I treatment was stopped faster in patient 1 than it was in patient 2, whose FVIII inhibitor titer was higher than patient 1’s. Two patients died: patient 3 due to brain infarction after recurrence associated with the development of sigmoid colon rupture, and patient 4 due to multiple organ failure associated with Clostridium difficile colitis. DPP4-I treatment may create an ideal environment for the induction of new antibodies and AHA onset associated with tumor necrosis factor-α reduction. These are the first reported cases of the potential development and/or prolonging of AHA after DDP4-I treatment for DM, and they suggest possible disease associations.
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U2 - 10.1007/s13300-019-0609-3
DO - 10.1007/s13300-019-0609-3
M3 - Article
AN - SCOPUS:85071682245
VL - 10
SP - 1139
EP - 1143
JO - Diabetes Therapy
JF - Diabetes Therapy
SN - 1869-6953
IS - 3
ER -
