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Hello, my name is Roland Herzog.
I'm the Director of the Gene and Cell Therapy Program at
the Hermann B. Wells Center for Pediatric Research at Indiana University.
I would like to talk to you about immune tolerance induction to coagulation factor VIII.
Our body is able to heal injuries that
happen to our blood vessels by forming a blood clot.
The formation of this blood clot that seals
an injured vessel requires a cascade of enzymatic reaction that happen in the blood,
and the proteins that carry out these reactions are referred to as coagulation factors.
It turns out that if one of these coagulation factors is defective,
the blood loses the ability to clot.
For example, factor IX is an enzyme that is
part of this cascade that is critical to carry out one of these reactions,
and it has a cofactor called factor VIII,
which is required for factor IX to function properly.
Deficiencies through genetic mutations in either of these two proteins
disrupt the coagulation cascade so that the blood is no longer able to properly clot.
As a result, patients with mutations in either factor VIII or IX,
are born with a bleeding disorder called hemophilia.
In the case of factor VIII deficiency,
which is the more common form of the two diseases,
the disease is called hemophilia A.
Because both genes are X-linked,
it is boys that are born with the disease,
whereas females are carriers.
The incidence of hemophilia worldwide is approximately one in 5,000 male births.
The severity of the disease correlates with the levels of coagulation.
In other words, a more serious mutation which
results in greater loss of the ability of the blood to clot,
will result in more severe disease,
and those patients who have less than one percent of
normal coagulation activity will bleed frequently.
In this case, the disease is characterized by frequent spontaneous bleeding episodes,
which often occur into joints and soft tissues.
An example is shown here with a child having a joint bleed,
and bleeding into closed spaces can actually be fatal.