Acquired
hemophilia is a serious coagulopathy usually affecting the elderly, persons with autoimmune disorders and, infrequently, women in the immediate postpartum period. It is due to
autoantibodies directed against specific domains of the
factor VIII molecule, leading to inhibition of
factor VIII binding to
von Willebrand factor, to
activated factor IX or to negatively charged
phospholipids. This results in
bleeding into the skin, muscles, gastrointestinal and genitourinary tracts, and other sites. Mixing patient plasma with normal plasma prolongs the activated partial thromboplastin time of the normal plasma and the Bethesda assay provides a quantitative estimate of the strength of the inhibitor. The selection of therapeutic concentrates for the management of acute
bleeding is related to the titer of the inhibitor; if less than 5 Bethesda Units, human
factor VIII may be effective, but higher titer inhibitors usually respond only to porcine
factor VIII,
recombinant factor VIIa or activated
prothrombin complex concentrates.
Corticosteroid treatment leads to disappearance of the
autoantibody in 50% of patients;
cyclophosphamide and
cyclosporine are effective in many who do not respond to
steroids. Occasionally, high dose
intravenous immunoglobulin or
immunosorbent columns transiently decrease inhibitor titers and enable control of
bleeding. Other
autoantibodies have been described against factors V, VII, XI and, rarely,
factor XIII and
prothrombin. New approaches in the management of
autoimmune disease and, especially, methods to establish tolerance are in development.