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

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.

Patient profile, clinical characteristics and treatment response in acquired haemophilia A: A retrospective analysis of a single‐centre experience over a 3‐year period

“…10 In the GTH-AH prospective registry study conducted by Tiede et al among 102 patients with AHA, PR and CR were reported to be achieved in 83% and 61% of patients, respectively. 13 Notably, authors also emphasized high prevalence of autoimmune diseases and malignancy as underlying conditions and unsatisfactorily high rate of infection-related mortality in AHA patients, despite the achievement of CR after immunosuppressive therapy. 8 In a study by Zeitler et al, the overall response rate among patients with AHA was reported to be 95%, while the authors also emphasized a difference in prognosis depending on the aetiology, with lower response rates in patients with underlying malignancy than in those with idiopathic AHA.…”

“…11 In a retrospective study conducted among 25 patients with AHA over 12 years (1997-2008) by Tay et al, an ORR was reported to be 83% along with relapse rate of 33% and overall mortality of 25%. 13 Concomitant diseases, side effects of therapy and serious haemorrhage are the likely causes of death, while the cause of death is unknown in many AHA cases, reflecting limited follow-up in most studies. 12 In another retrospective study by Ogawa et al in 25 patients with AHA over 17 years (1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015), rates for CR, relapse and death were reported in 91.7%, 12% and 28% of patients, respectively.…”

“…12 In another retrospective study by Ogawa et al in 25 patients with AHA over 17 years (1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015), rates for CR, relapse and death were reported in 91.7%, 12% and 28% of patients, respectively. 13 Notably, authors also emphasized high prevalence of autoimmune diseases and malignancy as underlying conditions and unsatisfactorily high rate of infection-related mortality in AHA patients, despite the achievement of CR after immunosuppressive therapy. 13 Concomitant diseases, side effects of therapy and serious haemorrhage are the likely causes of death, while the cause of death is unknown in many AHA cases, reflecting limited follow-up in most studies.…”

An anti‐factor IXa/factor X bispecific antibody, emicizumab, improves ex vivo coagulant potentials in plasma from patients with acquired hemophilia A

“…According to the European Acquired Haemophilia (EACH2) Registry, fatal bleeds were seen in 3.2% of enrolled patients, corresponding to 17.2% of all deaths . AHA is a rare condition with an estimated incidence of ~1.5 per million populations per year, but the number of patients with AHA appears to be increasing in Japan …”

“…4 AHA is a rare condition with an estimated incidence of ~1.5 per million populations per year, 5 but the number of patients with AHA appears to be increasing in Japan. 6 The EACH2 Registry suggested that the bypassing agents, recombinant FVIIa and activated prothrombin complex concentrate were similarly effective (>90%) for hemostatic management of acute bleeding in AHA. 7 However, the efficacy of these products appears to be inconsistent in individual patients, and many predisposing factors appear to contribute to variable responses.…”