Now we'll cover hemophilia.
Hemophilia is a rare disorder in which blood doesn't clot
normally because it lacks sufficient blood clotting proteins.
These are your clotting factors.
This results in longer bleeding times, puts patients
at risk for internal bleeding, can be life-threatening
and it can be treated with the
replacement of the missing clotting factors.
Let's talk about hemophilia.
Typically it's a factor VIII deficiency but there can
be other factors involved and we'll talk about that.
These patients could be missing a defective
gene on their factor VIII clotting protein.
There can be one in 5000 births this can present
and all races and ethnic groups can be affected.
So genetics cause two-thirds of the cases.
And there's another option, a third of the cases are
acquired and this is a spontaneous genetic mutation.
This happens at some point in the patient's
life and this will cause them to have hemophilia.
These patients are not born with the
gene mutation that causes hemophilia.
There are different types:
Hemophilia A - this is the most common and this is
classic, these patients have a factor VIII deficiency.
The next type is hemophilia B, also known
as Christmas disease and this is less common.
This is a factor IX deficiency.
And finally hemophilia C, this is a mild form.
This is a factor XI deficiency and this
can be passed to male and female children.
First we'll discuss acquired hemophilia which
is approximately a third of the hemophilia cases.
This is a rare form of hemophilia
and it's different than the genetic forms.
It's going to affect men and women equally.
The acquired form is not caused
by an inherited genetic mutation
instead it's a spontaneous mutation
that usually happens in adulthood
where the body starts making, mistaking antibodies
that attack and disable the clotting factor VIII.
This can be life-threatening as the
bleeding can be severe and unexpected
and healthcare professionals may
not recognise that this is happening
and this can cause a delay in
the diagnosis and the interventions.
In addition, in contrast to patients
who were born with hemophilia,
these patients likely do not know
they've even acquired this condition
and that puts them at a huge risk for bleeding.
It's not clear how many patients with acquired
hemophilia die as a consequence of their bleeding
but the estimates are between VIII and 22%.
So what are the causes of acquired hemophilia?
Well pregnancy, certain autoimmune disorders,
cancer or reaction to certain medications,
other - the general category, and unknown etiology
which is about 50% of the cases, we just don't know.
As you can see here, there a lot of
possible causes of acquired hemophilia
here in the green you're going to see that the
unknown causes account for about half of the cases.
Now that we've talked about the third of hemophilia cases
that are acquired in adulthood and develop spontaneously,
now we'll talk about the
genetic forms of hemophilia
Hemophilia A and B are inherited
in an X-linked recessive pattern.
The genes associated with hemophilia
are found on the X chromosome.
Chromosomes come in pairs.
We know females have two X chromosomes
while males have one X and one Y chromosome.
Only the X chromosome carries
the genes related to clotting factors.
A male who has hemophilia gene on his
only X chromosome will have hemophilia
since he only has one copy of the gene
and that is sufficient to cause the condition.
Females however, have two X chromosomes so a mutation
would have to occur on both copies of the gene
in order to cause the disorder.
Because this is unlikely that the female's
gonna have two altered copies of this gene,
it is very rare for females to
have the genetic form of hemophilia.
This pedigree shows one example
of how hemophilia can be inherited.
In this example, the father does not have hemophilia,
he has two normal chromosomes - an X and a Y
and the mother is a carrier of hemophilia which
means she only has one gene that's diseased
and one normal X chromosome.
Remember, this is a disorder
linked to the sex chromosomes
so the gender of the child will change
the odds of them inheriting this disorder.
Each daughter has a 50% chance of inheriting the
hemophilia gene from her mother and being a carrier.
And each son has a 50% chance of
inheriting the hemophilia gene from his mother
and having hemophilia because remember,
he only needs the one mutated gene.
The mother who was a carrier of the hemophilia
gene may not even know that she has this mutation
because she's likely asymptomatic.
This pedigree shows another example
of a way for hemophilia to be inherited.
In this example, the father has hemophilia, he
has the hemophilia gene on his only X chromosome.
The mother isn't a hemophilia carrier
because she has two normal X chromosomes.
Each daughter will inherit the hemophilia
gene from her father and be a carrier.
None of the sons will inherit
hemophilia from their father
because they will get the Y chromosome
from their dad, thus they'll be alright.
Hemophilia A, remember this is a
change in the gene that makes factor VIII
and hemophilia B is a change
in the gene that makes Factor IX.
Here we see a blood vessel up
top, it's broken, there is an injury.
On the left, usually these clotting factors are
gonna start working to begin the clotting process.
A clot will form including
fibrin and other substances.
But on the right, you see these
patients have an altered or missing protein
that can't participate effectively in the clotting
process so their bleeding is hard to control.
Now let's compare normal clotting
with patients who have hemophilia.
So let's say they get an injury, maybe they're cooking
something in the kitchen and they cut the hand with a knife.
That's a vascular injury, initially
they're gonna bleed the same amount.
Their body's gonna respond immediately by trying
to vasoconstrict to slow the bleeding to this wound,
and that step is the same.
This is when things start to change - the patient who
has normal clotting is going to develop a platelet plug.
The patient with hemophilia is gonna
have dysfunctional clotting cascades
and incomplete platelet plugs
and they are going to keep bleeding.
Finally the patient without
hemophilia is gonna form their fibrin clot
while the patient with hemophilia is gonna have
incomplete or delayed formation of the fibrin clot
and they are gonna keep bleeding.