International study on etiology of inhibitors in patients with a moderate or mild form of hemophilia A, influences of immunogenetic and hemophilia treatment factors.

The development of inhibiting antibodies (inhibitors) represents a major
challenge in the management of hemophilia. In patients with moderate/mild
hemophilia A the inhibitor incidence seems to be rising. Since the prevalence
of moderate/mild hemophiliacs is relatively high, the clinical impact of this
problem is substantial. Several investigators have suggested that extensive
factor VIII replacement in surgical patients may increase the risk of inhibitor
development. However, a number of important questions remain unanswered. It is
important to know which clinical and genetic factors lead to inhibitor
development, because this may ultimately help reduce the risk by preventive
measures.

The aims of this project are:

A. To describe the incidence of inhibitor formation in moderate/mild hemophilia
A patients.

B. To identify clinical and genetic factors that induce inhibitor formation in
patients with moderate/mild hemophilia A.

C. To characterize T cell epitopes in patients with moderate or mild hemophilia
A and inhibitory antibodies.

This project consists of three international multicenter studies:

A. A cohort study to describe the incidence of inhibitor formation in
moderate/mild hemophilia A patients.

B. A case-control study to identify clinical and genetic factors that induce
inhibitor formation in patients with moderate/mild hemophilia A.

C. Experimental study to characterize T cell epitopes in patients with moderate
or mild hemophilia A and inhibitory antibodies.

The only burden of the case-control and experimental study is the drawing of
one extra tube of blood at a moment of regular blood sampling for clincial
reasons. This is in proportion to the potential value of the study.
The results of the study may be relevant in the future for prevention of
inhibiting antibodies in patients with mild/moderate hemophilia.