International Journal of Hematology

, Volume 106, Issue 1, pp 82–89 | Cite as

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

  • Yoshiyuki Ogawa
  • Kunio Yanagisawa
  • Hideki Uchiumi
  • Takuma Ishizaki
  • Takeki Mitsui
  • Fumito Gouda
  • Masahiro Ieko
  • Akitada Ichinose
  • Yoshihisa Nojima
  • Hiroshi Handa
Original Article


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.


Acquired hemophilia A Coagulation factor VIII Immunosuppressive therapy Rituximab Autoimmune disease 


  1. 1.
    Green D, Lechner K. A survey of 215 non-hemophilic patients with inhibitors to Factor VIII. Thromb Haemost. 1981;45:200–3.PubMedGoogle Scholar
  2. 2.
    Collins PW. Management of acquired haemophilia A. J Thromb Haemost. 2011;9(suppl 1):226–35.CrossRefPubMedGoogle Scholar
  3. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 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.CrossRefPubMedGoogle Scholar
  5. 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.CrossRefPubMedGoogle Scholar
  6. 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.CrossRefPubMedGoogle Scholar
  7. 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.CrossRefPubMedGoogle Scholar
  8. 8.
    Franchini M. Rituximab in the treatment of adult acquired hemophilia A: a systematic review. Crit Rev Oncol Hematol. 2007;63:47–52.CrossRefPubMedGoogle Scholar
  9. 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.CrossRefPubMedGoogle Scholar
  10. 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).CrossRefGoogle Scholar
  11. 11.
    Franchini M, Lippi G. Acquired factor VIII inhibitors. Blood. 2008;112:250–5.CrossRefPubMedGoogle Scholar
  12. 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).CrossRefGoogle Scholar
  13. 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.CrossRefPubMedGoogle Scholar
  14. 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.CrossRefPubMedGoogle Scholar
  15. 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. 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).CrossRefGoogle Scholar
  17. 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).PubMedGoogle Scholar
  18. 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).PubMedGoogle Scholar
  19. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 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.PubMedGoogle Scholar
  21. 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.CrossRefPubMedGoogle Scholar
  22. 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.CrossRefPubMedGoogle Scholar
  23. 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.PubMedGoogle Scholar
  24. 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.CrossRefPubMedGoogle Scholar
  25. 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.CrossRefPubMedGoogle Scholar
  26. 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.PubMedGoogle Scholar
  27. 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.PubMedPubMedCentralGoogle Scholar
  28. 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.PubMedPubMedCentralGoogle Scholar

Copyright information

© The Japanese Society of Hematology 2017

Authors and Affiliations

  • Yoshiyuki Ogawa
    • 1
    • 2
  • Kunio Yanagisawa
    • 1
  • Hideki Uchiumi
    • 1
  • Takuma Ishizaki
    • 1
  • Takeki Mitsui
    • 1
  • Fumito Gouda
    • 3
  • Masahiro Ieko
    • 2
    • 4
  • Akitada Ichinose
    • 2
    • 5
  • Yoshihisa Nojima
    • 6
  • Hiroshi Handa
    • 1
  1. 1.Department of Medicine and Clinical SciencesGunma University Graduate School of MedicineMaebashiJapan
  2. 2.The Japanese Collaborative Research Group (JCRG) on Acquired Coagulopathies Supported by the Japanese Ministry of Health, Labour and WelfareYamagataJapan
  3. 3.Department of Internal MedicineNational Hospital Organization Takasaki General Medical CenterTakasakiJapan
  4. 4.Department of Internal Medicine, School of DentistryHealth Sciences University of HokkaidoSapporoJapan
  5. 5.Department of Molecular Patho-Biochemistry and Patho-BiologyYamagata University School of MedicineYamagataJapan
  6. 6.Renal DivisionJapan Red Cross Maebashi HospitalMaebashiJapan

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