Acquired hemophilia A is a rare but life threatening hemorrhagic disorder caused by the spontaneous appearance of auto-antibodies directed against the endogenous plasma coagulation factor VIII
(Kessler CM. Acquired factor VIII autoantibody inhibitors: current concepts and potential therapeutic strategies for the future. Haematologica 2000;85 (10 Suppl):57-61; discussion 3).

The structure of an antibody/immunoglobulin is given below.

Anti-factor VIII autoantibodies are detected by their ability to inhibit factor VIII pro-coagulant activity in plasma, and are referred to as factor VIII inhibitors. Inhibitors to endogenous factor VIII develop in about one per million individuals each year.
(Franchini, AJH, 2005; Collins Blood 2006).


In up to 50% of the cases, they occur spontaneously without an underlying medical condition. In the remaining cases, they develop in association with autoimmune disorders, malignancies, and drugs, or during the postpartum period. Acquired hemophilia A has a reported mortality between 6.2% and 44.3% (Green, Thromb Haemost 1981, Morrison, Blood, 1993, Collins, Blood 2006). FVIII inhibitors also arise in patients with congenital hemophilia A as alloantibodies directed to therapeutically administered exogenous factor VIII. Autoantibodies and alloantibodies against factor VIII share similar properties with respect to their isotypic distribution and mechanisms of inhibition of the activity of factor VIII. They may however differ in their epitope specificities and kinetics of factor VIII inactivation (Shapiro, JCI, 1967; Fulscher, Blood 1987, Scandella, Throm Res, 2001).

Catalytic antibodies are immunoglobulins with a capacity to hydrolyze the antigen for which they are specific. The presence of factor VIII-hydrolyzing IgG has been reported in about 50% of the patients with congenital severe hemophilia A, who have developed FVIII inhibitors following substitution therapy with exogenous factor VIII.
(Sébastien Lacroix-Desmazes, Nature Medicine, 1999)

A cartoon of coagulation factor VIII is shown...

The rate of factor VIII hydrolysis was shown to correlate with the inhibitory activities scored in the plasma of the patients (Sébastien Lacroix-Desmazes, NEJM, 2002). The kinetics of factor VIII degradation by factor VIII-hydrolyzing IgG were compatible with a pathogenic role for catalytic antibodies in inactivation of the therapeutically administered factor VIII (Sébastien Lacroix-Desmazes, JI, 2006).

My work is to investigate the presence and prevalence of factor VIII-hydrolyzing IgG in a French cohort of patients with acquired hemophilia A.