title: Twelve years of experience of acquired hemophilia A: trials and tribulations in South Australia.
abstract: Acquired hemophilia A (AH) is a rare and serious acquired bleeding disorder where prompt and correct diagnosis is crucial, and immune suppression is often required for factor VIII (FVIII) autoantibody eradication. The acquired FVIII deficiency usually manifests as bruises and bleeding, and treatment such as FVIII has limited efficacy because of the neutralizing FVIII inhibitor. Expensive bypassing agents such as recombinant activated factor VII (rFVIIa) may be required to treat clinically significant bleeding. This report summarizes the experience related to AH from a large Australian hemophilia center based in South Australia. We identified 25 patients retrospectively over 12 years (1997 to 2008) and reviewed diagnostic features, treatment for bleeds and to eradicate the autoantibody, treatment response, and survival outcomes. The incidence in South Australia was 1.20 cases per million/year with a median age of 78 years with an approximately equivalent sex ratio (12 males versus 13 females); median FVIII and inhibitor titer were 2.5 IU/dL and 11.0 BU/mL, respectively. Twenty-four patients were evaluated further. Thirteen patients (54%) required hemostatic agents, and rFVIIa was used in seven for major bleeds, of which four were limb or life threatening. Eighteen patients were treated by hematologists with immune suppression, and combination steroid and azathioprine was used most commonly to eradicate autoantibody; 15 of these 18 achieved remission (i.e., 83% response rate). Two patients had persistent low-titer inhibitor when treatments were withdrawn, and one died of a fatal bleed shortly after starting treatment. One had spontaneous remission. Five patients (33%) relapsed, three in less than 6 months after starting treatment; all were retreated successfully. Rituximab was used in six patients for high-titer inhibitor, second relapse, two life-threatening bleeds, underlying lymphoma, and steroid intolerance, respectively. Overall mortality was 25% ( N = 6), five of whom were not treated. Advanced age and lack of treatment were predictive of poor survival outcomes. The very elderly (>75 years of age) may warrant a different treatment modality such as rituximab, which is potentially more tolerable and efficacious.
authors.affiliation: Division of Haematology, SA Pathology, South Australia, Australia. lay.tay@imvs.sa.gov.au
authors.forename: Lay
authors.initials: L
authors.lastname: Tay
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Duncan
authors.forename: Deepak
authors.initials: D
authors.lastname: Singhal
authors.forename: Reem
authors.initials: R
authors.lastname: Al-Qunfoidi
authors.forename: Douglas
authors.initials: D
authors.lastname: Coghlan
authors.forename: Wilfred
authors.initials: W
authors.lastname: Jaksic
authors.forename: Ferenz
authors.initials: F
authors.lastname: Szabo
authors.forename: Simon
authors.initials: S
authors.lastname: McRae
authors.forename: John
authors.initials: J
authors.lastname: Lloyd
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies / Q000032:analysis*; D001379:Azathioprine / Q000627:therapeutic use; D005169:Factor VIII / Q000276:immunology; D015942:Factor VIIa / Q000627:therapeutic use; D005260:Female; D006467:Hemophilia A / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D012189:Retrospective Studies; D000069283:Rituximab; D013021:South Australia / Q000453:epidemiology; D013256:Steroids / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies; D007166:Immunosuppressive Agents; D011994:Recombinant Proteins; D013256:Steroids; D000069283:Rituximab; D005169:Factor VIII; C103587:recombinant FVIIa; D015942:Factor VIIa; D001379:Azathioprine