HAEMOSTASIS AND THROMBOSIS
Acquired hemophilia A
Servizio di Immunoematologia e Trasfusione, Centro Emofilia, Azienda Ospedaliera di Verona, Verona, Italy
(Received 19 September 2005; accepted 25 November 2005)
Acquired hemophilia A is a rare but severe autoimmune bleeding disorder, resulting from the presence of autoantibodies
directed against clotting factor VIII. The etiology of the disorder remains obscure, although approximately half of all cases are
associated with other underlying conditions. A prompt diagnosis and appropriate management enable effective control of this
acquired hemorrhagic disorder: the aims of therapy are to terminate the acute bleeding episode and eliminate or reduce the
inhibitor. The recent availability of bypassing agents, first activated prothrombin complex concentrates and then recombinant
activated factor VII, has significantly reduced mortality during the acute phase of the disease in patients with high titer
inhibitors. On another front, immunosuppressive therapy (corticosteroids and cytotoxic agents, alone or in various
combinations) has resulted in long-term inhibitor suppression in up to 70% of the cases. Moreover, new therapeutic strategies
(anti-CD20 monoclonal antibody and immune tolerance protocols) are very promising and mayfurther improvethe prognosis
of acquired hemophilia A.
Keywords: Acquired, hemophilia, factor VIII, bleeding, treatment
Acquired hemophilia A is an uncommon but poten-
tially life-threatening hemorrhagic disorder caused by
the development of autoantibodies (mostly IgG)
directed against the coagulation factor VIII (FVIII)
[1–7]. The incidence of acquired hemophilia A has
per year, but this figure may be an underestimate given
the difficulty in making the diagnosis. The clinical
picture is dominated by severe hemorrhage in the
rate of up to 22% [8–13]; most of these deaths occur
within the first few weeks after presentation. However,
the reduction in mortality rate observed in the most
the management of acute bleeding during the last few
years (first porcine factor VIII and prothrombin
complex concentrates [PCC] and then recombinant
activated factor VII [rFVIIa]) [14,15]. Nevertheless,
underestimated due to the high median age at the
time of diagnosis (60–70 years old).
The age distribution of autoantibodies is typically
biphasic with a small peak between 20 and 30 years
(postpartum inhibitors) and a major peak in patients
aged 68–80 years [1,3]. Factor VIII inhibitors are
distributed equally by sex, although females pre-
dominate in the younger age group because of the
association with pregnancy while males constitute the
majority of patients over the age of 60 . However,
it is difficult to draw any firm conclusions as regards
epidemiology, clinical aspects and therapy of this
disease from literature data, since most of the reports
are anecdotal and describe only a few cases.
In this review, we briefly report present knowledge
about acquired hemophilia A, analyzing its epidemio-
logy, pathogenesis, diagnostic and clinicalfeatures.We
ISSN 1024-5332 print/ISSN 1607-8454 online q 2006 Taylor & Francis
Correspondence: M. Franchini, Servizio di Immunoematologia e Trasfusione, Centro Emofilia, Ospedale Policlinico, Piazzale L.Scuro,
10, 37134 Verona, Italy. Tel: 39 45 8073610. Fax: 39 45 8073612. E-mail: email@example.com
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Acquired hemophilia A