title: Acquired hemophilia A: a frequently overlooked autoimmune hemorrhagic disorder.
abstract: Acquired hemophilia A (AHA) is a rare hemorrhagic disease in which autoantibodies against coagulation factor VIII- (FVIII-) neutralizing antibodies (inhibitors) impair the intrinsic coagulation system. As the inhibitors developed in AHA are autoantibodies, the disease may have an autoimmune cause and is often associated with autoimmune disease. Although acute hemorrhage associated with AHA may be fatal and is costly to treat, AHA is often unrecognized or misdiagnosed. AHA should thus be considered in the differential diagnosis particularly in postpartum women and the elderly with bleeding tendency or prolonged activated partial thromboplastin time. Cross-mixing tests and measurement of FVIII-binding antibodies are useful to confirm AHA diagnosis. For treatment of acute hemorrhage, hemostatic therapy with bypassing agents should be provided. Unlike in congenital hemophilia A with inhibitors, in which immune tolerance induction therapy using repetitive infusions of high-dose FVIII concentrates is effective for inhibitor eradication, immune tolerance induction therapy has shown poor efficacy in treating AHA. Immunosuppressive treatment should thus be initiated to eradicate inhibitors as soon as the diagnosis of AHA is confirmed.
authors.affiliation: Department of Pediatrics, Matsubara Tokushukai Hospital, 7-13-26 Amamihigashi, Matsubara, Osaka 580-0032, Japan.
authors.forename: Yoshihiko
authors.identifier: 0000-0002-1773-5535
authors.initials: Y
authors.lastname: Sakurai
authors.affiliation: Department of Clinical Laboratory Science, Kansai University of Health Sciences, 2-11-1 Wakaba, Kumatori, Osaka 590-0433, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Takeda
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000150:complications / Q000276:immunology; D005169:Factor VIII / Q000276:immunology; D005260:Female; D006467:Hemophilia A / Q000175:diagnosis / Q000209:etiology* / Q000628:therapy; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000150:complications / Q000276:immunology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D001323:Autoantibodies; D005169:Factor VIII
references.citation: Ann Hematol. 2001 Nov;80(11):691-3
references.pmid: 11757731
references.citation: Semin Thromb Hemost. 2013 Mar;39(2):191-201
references.pmid: 23397553
references.citation: Br J Haematol. 1996 Jun;93(3):688-93
references.pmid: 8652395
references.citation: Eur J Immunol. 2002 Jul;32(7):2004-10
references.pmid: 12115621
references.citation: Thromb Res. 1996 Aug 15;83(4):279-86
references.pmid: 8870172
references.citation: Immunity. 2004 Apr;20(4):441-53
references.pmid: 15084273
references.citation: Thromb Haemost. 2009 Feb;101(2):408-10
references.pmid: 19190830
references.citation: Med Sci Monit. 2007 Apr;13(4):RA55-61
references.pmid: 17392659
references.citation: J Immunol. 2008 Jun 1;180(11):7714-20
references.pmid: 18490775
references.citation: J Immunol. 2006 Jul 15;177(2):1355-63
references.pmid: 16818797
references.citation: J Thromb Haemost. 2011 Jul;9 Suppl 1:226-35
references.pmid: 21781259
references.citation: Clin Lab Haematol. 1999 Apr;21(2):125-8
references.pmid: 10342072
references.citation: Theor Biol Med Model. 2006 Jun 07;3:22
references.pmid: 16759382
references.citation: Hematology. 2006 Apr;11(2):119-25
references.pmid: 16753853
references.citation: Autoimmun Rev. 2014 Jan;13(1):40-8
references.pmid: 23954454
references.citation: Haemophilia. 2008 Mar;14(2):355-60
references.pmid: 18081831
references.citation: J Thromb Haemost. 2007 May;5(5):893-900
references.pmid: 17461924
references.citation: J Thromb Haemost. 2006 Feb;4(2):295-306
references.pmid: 16420554
references.citation: Br J Haematol. 1975 Feb;29(2):329-40
references.pmid: 1191553
references.citation: Vox Sang. 1999;77 Suppl 1:57-64
references.pmid: 10529691
references.citation: Haemophilia. 2007 Sep;13(5):451-61
references.pmid: 17880429
references.citation: J Clin Invest. 1993 Jan;91(1):61-8
references.pmid: 7678610
references.citation: Int J Immunopathol Pharmacol. 2007 Jan-Mar;20(1):1-8
references.pmid: 17346422
references.citation: Blood. 2009 Mar 12;113(11):2587-94
references.pmid: 19144987
references.citation: Blood. 1993 Sep 15;82(6):1767-75
references.pmid: 7691236
references.citation: Am J Clin Pathol. 1985 Jun;83(6):697-706
references.pmid: 3923823
references.citation: Blood Coagul Fibrinolysis. 1994 Aug;5(4):523-7
references.pmid: 7841308
references.citation: Hum Immunol. 2007 Jul;68(7):586-91
references.pmid: 17584580
references.citation: Thromb Haemost. 2002 Oct;88(4):568-75
references.pmid: 12362225
references.citation: Rinsho Byori. 2009 Oct;57(10):990-8
references.pmid: 19928497
references.citation: BMC Res Notes. 2010 Jun 07;3:161
references.pmid: 20529258
references.citation: Am J Hematol. 2006 Oct;81(10):768-73
references.pmid: 16868941
references.citation: Br J Haematol. 2006 Jun;133(6):591-605
references.pmid: 16704433
references.citation: Thromb Haemost. 1995 Feb;73(2):247-51
references.pmid: 7792738
references.citation: Haematologica. 2009 Apr;94(4):566-75
references.pmid: 19336751
references.citation: Blood. 2011 Feb 17;117(7):2257-64
references.pmid: 21131590
references.citation: J Thromb Haemost. 2011 Jul;9 Suppl 1:216-25
references.pmid: 21781258
references.citation: Blood. 1989 Oct;74(5):1618-26
references.pmid: 2477082
references.citation: Curr Med Chem. 2012;19(12):1792-803
references.pmid: 22414087
references.citation: FEBS Lett. 2009 Aug 6;583(15):2565-72
references.pmid: 19595998
references.citation: Semin Thromb Hemost. 2009 Nov;35(8):806-13
references.pmid: 20169517
references.citation: Haemophilia. 2006 Dec;12 Suppl 6:30-5; discussion 35-6
references.pmid: 17123391
references.citation: Proc Natl Acad Sci U S A. 1985 Nov;82(22):7728-32
references.pmid: 2415970
references.citation: Haematologica. 2000 Oct;85(10):1045-50
references.pmid: 11025595
references.citation: Blood. 2005 Mar 15;105(6):2287-93
references.pmid: 15542586
references.citation: Haematologica. 1994 Nov-Dec;79(6):550-6
references.pmid: 7896216
references.citation: Haemophilia. 2001 Jan;7(1):26-32
references.pmid: 11136377
references.citation: Patient Saf Surg. 2009 May 22;3(1):8
references.pmid: 19463180
references.citation: Haematologica. 2004 Jun;89(6):696-703
references.pmid: 15194537
references.citation: Semin Thromb Hemost. 2009 Nov;35(8):769-77
references.pmid: 20169513
references.citation: Semin Thromb Hemost. 2011 Jun;37(4):382-8
references.pmid: 21805444
references.citation: Baillieres Clin Haematol. 1996 Jun;9(2):331-54
references.pmid: 8800509
references.citation: Blood. 2009 Mar 26;113(13):2873-4
references.pmid: 19324909
references.citation: Br J Haematol. 2010 Jan;148(2):183-94
references.pmid: 19814739
references.citation: Am J Hematol. 2005 Sep;80(1):55-63
references.pmid: 16138334
references.citation: Curr Opin Hematol. 1999 Sep;6(5):314-22
references.pmid: 10468147
references.citation: Autoimmun Rev. 2011 Apr;10(6):311-6
references.pmid: 21115138
references.citation: Blood. 2006 Apr 15;107(8):3235-42
references.pmid: 16357320
references.citation: Br J Haematol. 2003 Apr;121(1):21-35
references.pmid: 12670328
references.citation: Blood. 2008 Jul 15;112(2):250-5
references.pmid: 18463353
references.citation: Immunol Rev. 2008 Jun;223:143-55
references.pmid: 18613834
references.citation: Thromb Diath Haemorrh. 1975 Nov 15;34(2):612
references.pmid: 1198543
references.citation: Vox Sang. 1994;66(1):8-13
references.pmid: 8146988
references.citation: N Engl J Med. 2002 Feb 28;346(9):662-7
references.pmid: 11870243
references.citation: Crit Rev Oncol Hematol. 2007 Jul;63(1):47-52
references.pmid: 17236786
references.citation: Haemophilia. 2004 Mar;10(2):169-73
references.pmid: 14962206
references.citation: J Clin Invest. 2002 Jan;109(1):59-68
references.pmid: 11781351
references.citation: Blood. 2007 Mar 1;109(5):1870-7
references.pmid: 17047148
references.citation: Clin Adv Hematol Oncol. 2012 Jan;10(1):19-27
references.pmid: 22398803
references.citation: Thromb Haemost. 1993 Nov 15;70(5):753-7
references.pmid: 8128430