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Clinical characteristics and outcomes of acquired hemophilia A: experience at a single center in Japan

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Abstract

Acquired hemophilia A (AHA), which is caused by autoantibodies against coagulation factor VIII (FVIII) is a rare, life-threatening bleeding disorder, the incidence of which appears to be increasing in Japan as the population ages. However, the clinical characteristics, treatment, and outcomes of AHA remain difficult to establish due to the rarity of this disease. We retrospectively analyzed data from 25 patients (median age 73 years; range 24–92 years; male n = 15) diagnosed with AHA between 1999 and 2015 at Gunma University Hospital. We identified autoimmune diseases and malignancy as underlying conditions in four and three patients, respectively. Factor VIII activity was significantly decreased in all patients (median 2.0%; range <1.0-8.0) by FVIII inhibitor (median 47.0 BU/mL; range 2.0–1010). Among 71 bleeding events, subcutaneous or intramuscular hemorrhage was the most prevalent. Seventeen patients required bypassing agents. Twenty-two (91.7%) of 24 patients treated with immunosuppressive agents achieved complete response (CR) during a median of 57.5 days (range 19–714 days). Although three patients (12%) relapsed and seven (28%) died of infection, none of the deaths were related to bleeding. Although most of our patients achieved CR after immunosuppressive therapy, the rate of infection-related mortality was unsatisfactorily high.

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References

  1. Green D, Lechner K. A survey of 215 non-hemophilic patients with inhibitors to Factor VIII. Thromb Haemost. 1981;45:200–3.

    CAS  PubMed  Google Scholar 

  2. Collins PW. Management of acquired haemophilia A. J Thromb Haemost. 2011;9(suppl 1):226–35.

    Article  PubMed  Google Scholar 

  3. Collins P, Baudo F, Huth-Kühne A, Ingerslev J, Kessler CM, Castellano ME, et al. Consensus recommendations for the diagnosis and treatment of acquired hemophilia A. BMC Res Notes. 2010;3:161.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Collins PW, Hirsch S, Baglin TP, Dolan G, Hanley J, Makris M, et al. Acquired hemophilia A in the United Kingdom: a 2-year national surveillance study by the United Kingdom Haemophilia Centre Doctors’ Organisation. Blood. 2007;109:1870–7.

    Article  CAS  PubMed  Google Scholar 

  5. Collins P, Macartney N, Davies R, Lees S, Giddings J, Majer R. A population based, unselected, consecutive cohort of patients with acquired hemophilia A. Br J Haematol. 2004;124:86–90.

    Article  PubMed  Google Scholar 

  6. Lottenberg R, Kentro TB, Kitchens CS. Acquired hemophilia. A natural history study of 16 patients with factor VIII inhibitors receiving little or no therapy. Arch Intern Med. 1987;147:1077–81.

    Article  CAS  PubMed  Google Scholar 

  7. Stasi R, Brunetti M, Stipa E, Amadori S. Selective B-cell depletion with rituximab for the treatment of patients with acquired hemophilia. Blood. 2004;103:4424–8.

    Article  CAS  PubMed  Google Scholar 

  8. Franchini M. Rituximab in the treatment of adult acquired hemophilia A: a systematic review. Crit Rev Oncol Hematol. 2007;63:47–52.

    Article  PubMed  Google Scholar 

  9. Baudo F, Collins P, Huth-Kühne A, Lévesque H, Marco P, Nemes L, et al. Management of bleeding in acquired hemophilia A: results from the European Acquired Haemophilia (EACH2) Registry. Blood. 2012;120:39–46.

    Article  CAS  PubMed  Google Scholar 

  10. Tanaka I, Amano K, Taki M, Oka T, Sakai M, Shirahata A, et al. A 3-year consecutive survey on current status of acquired inhibitors against coagulation factors in Japan—analysis of prognostic factors. Jpn J Thromb Hemost. 2008;19:140–53 (Japanese).

    Article  Google Scholar 

  11. Franchini M, Lippi G. Acquired factor VIII inhibitors. Blood. 2008;112:250–5.

    Article  CAS  PubMed  Google Scholar 

  12. Shima M, Tanaka I, Kawai Y, Tsuji H, Nakamura S, Morita T. A survey of acquired inhibitors of blood coagulation in Japan. Jpn J Thromb Hemost. 2003;14:107–21 (Japanese).

    Article  Google Scholar 

  13. Ichikawa S, Kohata K, Okitsu Y, Suzuki M, Nakajima S, Yamada MF, et al. Acquired hemophilia A with sigmoid colon cancer: successful treatment with rituximab followed by sigmoidectomy. Int J Hematol. 2009;90:33–6.

    Article  PubMed  Google Scholar 

  14. Makita S, Aoki T, Watarai A, Aida A, Katayama T, Danbara M, et al. Acquired hemophilia associated with autoimmune bullous disease: a report of two cases and a review of the literature. Intern Med. 2013;52:807–10.

    Article  PubMed  Google Scholar 

  15. Kobayashi C, Naitoh A, Watanabe A, Asai H, Mohri H. Three cases of acquired hemophilia A at our institute. J Jpn Soc Lab Hematol. 2015;16:282–92 (Japanese).

    Google Scholar 

  16. Seki Y, Miyakoshi S. A present state and clinical problems of long term outcome of patients with acquired hemophilia A in our hospital. Jpn J Thromb Hemost. 2016;27:64–9 (Japanese).

    Article  Google Scholar 

  17. Yanagisawa K, Ogawa Y, Mitsui T, Noguchi H, Shimizu H, Ishizaki T, et al. Remission of acquired hemophilia A following radiation therapy for esophageal cancer. Rinsho Ketsueki. 2016;57:451–5 (Japanese).

    PubMed  Google Scholar 

  18. Ogawa Y, Yanagisawa K, Ishizaki T, Naito C, Mihara M, Handa H, et al. Development of acquired hemophilia A during maintenance therapy for immune thrombocytopenia. Rinsho Ketsueki. 2016;57:456–60 (Japanese).

    PubMed  Google Scholar 

  19. Huth-Kühne A, Baudo F, Collins P, Ingerslev J, Kessler CM, Lévesque H, et al. International recommendations on the diagnosis and treatment of patients with acquired hemophilia A. Haematologica. 2009;94:566–75.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Kasper CK, Aledort L, Aronson D, Counts R, Edson JR, van Eys J, et al. Proceedings: A more uniform measurement of factor VIII inhibitors. Thromb Diath Haemorrh. 1975;34:612.

    CAS  PubMed  Google Scholar 

  21. Peerschke EI, Castellone DD, Ledford-Kraemer M, Van Cott EM, Meijer P. Laboratory assessment of factor VIII inhibitor titer: the North American Specialized Coagulation Laboratory Association experience. Am J Clin Pathol. 2009;131:552–8.

    Article  CAS  PubMed  Google Scholar 

  22. Schulman S, Kearon C. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost. 2005;3:692–4.

    Article  CAS  PubMed  Google Scholar 

  23. Arkin S, Blei F, Fetten J, Foulke R, Gilchrist GS, Heisel MA, et al. Human coagulation factor FVIIa (recombinant) in the management of limb-threatening bleeds unresponsive to alternative therapies: results from the NovoSeven emergency-use programme in patients with severe haemophilia or with acquired inhibitors. Blood Coagul Fibrinolysis. 2000;11:255–9.

    CAS  PubMed  Google Scholar 

  24. Takedani H, Shima M, Horikoshi Y, Koyama T, Fukutake K, Kuwahara M, et al. Ten-year experience of recombinant activated factor VII use in surgical patients with congenital haemophilia with inhibitors or acquired haemophilia in Japan. Haemophilia. 2015;21:374–9.

    Article  CAS  PubMed  Google Scholar 

  25. Wiestner A, Cho HJ, Asch AS, Michelis MA, Zeller JA, Peerschke EI, et al. Rituximab in the treatment of acquired factor VIII inhibitors. Blood. 2002;100:3426–8.

    Article  CAS  PubMed  Google Scholar 

  26. Onitilo AA, Skorupa A, Lal A, Ronish E, Mercier RJ, Islam R, et al. Rituximab in the treatment of acquired factor VIII inhibitors. Thromb Haemost. 2006;96:84–7.

    CAS  PubMed  Google Scholar 

  27. Bonfanti C, Crestani S, Frattini F, Sissa C, Franchini M. Role of rituximab in the treatment of postpartum acquired haemophilia A: a systematic review of the literature. Blood Transfus. 2015;13:396–400.

    PubMed  PubMed Central  Google Scholar 

  28. D’Arena G, Grrandone E, Di Minno MND, Musto P, Di Minno G. The anti-CD20 monoclonal antibody rituximab to treat acquired haemophilia A. Blood Transfus. 2016;14:255–61.

    PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine and Clinical Sciences, Gunma University Graduate School of Medicine, 3-39-22 Showa, Maebashi, Gunma, 371-8511, Japan

    Yoshiyuki Ogawa, Kunio Yanagisawa, Hideki Uchiumi, Takuma Ishizaki, Takeki Mitsui & Hiroshi Handa

  2. The Japanese Collaborative Research Group (JCRG) on Acquired Coagulopathies Supported by the Japanese Ministry of Health, Labour and Welfare, Yamagata, Japan

    Yoshiyuki Ogawa, Masahiro Ieko & Akitada Ichinose

  3. Department of Internal Medicine, National Hospital Organization Takasaki General Medical Center, Takasaki, Japan

    Fumito Gouda

  4. Department of Internal Medicine, School of Dentistry, Health Sciences University of Hokkaido, Sapporo, Japan

    Masahiro Ieko

  5. Department of Molecular Patho-Biochemistry and Patho-Biology, Yamagata University School of Medicine, Yamagata, Japan

    Akitada Ichinose

  6. Renal Division, Japan Red Cross Maebashi Hospital, Maebashi, Japan

    Yoshihisa Nojima

Authors
  1. Yoshiyuki Ogawa
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  2. Kunio Yanagisawa
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  3. Hideki Uchiumi
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  4. Takuma Ishizaki
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  5. Takeki Mitsui
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  6. Fumito Gouda
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  7. Masahiro Ieko
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  8. Akitada Ichinose
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  9. Yoshihisa Nojima
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  10. Hiroshi Handa
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Corresponding author

Correspondence to Yoshiyuki Ogawa.

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Ogawa, Y., Yanagisawa, K., Uchiumi, H. et al. Clinical characteristics and outcomes of acquired hemophilia A: experience at a single center in Japan. Int J Hematol 106, 82–89 (2017). https://doi.org/10.1007/s12185-017-2210-8

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  • DOI: https://doi.org/10.1007/s12185-017-2210-8

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