Okay, let’s switch gears now and
talk about the clotting cascade,
which really happens first,
but we’re presenting it in a
slightly backwards order.
So in the clotting cascade,
we have to recall that
there is an intrinsic pathway of clotting
and an extrinsic pathway of clotting.
I don’t think it’s so important
clinically to remember which
clotting factor goes to
which clotting factor
but there are 2 that are
very important to remember
and those are factors VIII and IX
which are circled on the slide.
You can see these are both
part of the intrinsic pathway
and thus, the PTT is
the test of choice
for determining whether patients have a
deficiency of either factor VIII or factor IX.
A deficiency of factor VIII or
factor IX is called hemophilia.
So, hemophilia A is a
deficiency of factor VIII
and hemophilia B is a
deficiency of factor IX.
Both of these diseases
are X-linked recessive.
That means almost always these are
male patients who have the disease
and females are simply carriers,
although very, very rarely
female can have the disease.
A variable severity exists with
patients with this disease.
They may have mild bleeding or they
may have very severe bleeding.
So we may expect to see a variety of
severity in patients with hemophilia.
So let’s look at how this
disease typically presents.
Especially on patients
with more severe disease,
it can absolutely present
in a newborn period.
Classically, about half
of undiagnosed infants,
infants who weren’t diagnosed
prenatally through genetic testing,
will present because of
bleeding after a circumcision.
So the circumcision is done, the child
bleeds excessively after the procedure
and the doctor puts two and
two together and says,
“Yeah, maybe this
baby has hemophilia.”
The patients may develop
intracranial hemorrhage at birth.
This is because they bleed excessively as a
result of a normal amount of birth trauma.
They may have a large cephalohematoma
or parents may notice that after
the umbilical stump falls off
between weeks one and four, that the
umbilical stump bleeds excessively.
There can be a later presentation
especially those in more mild disease.
They can present with hemarthrosis
or blood in the joint
and on average, patients present with their
first hemarthrosis around 10 months of age.
Hematomas can present, but not
usually bruising or petechiae,
that’s more consistent
In these patients, they simply
have a large swelling hematoma.
Patients may present
with a GI bleed
or they may present with
an intracranial bleed.
And keep that in mind, intracranial
bleed in a child with minimal trauma
might be hemophilia.
There are very rare cases reported
where people have such mild disease
that they don’t even present
well into adulthood,
but most people will present in
childhood, usually by the age of 4.
So what sort of spontaneous bleeds
can happen in these patients?
They could spontaneously have an
intracerebral bleed and that is devastating.
Those are usually the more severe patients.
They often have frequent
bleeding from nose and mouth,
again, the nose bleeds and the
bleeding after brushing their teeth
and they may have spontaneous joint bleeds,
which are real problem and we’ll
talk about that in a little bit.
Patients may also have
but what’s key is
these may be delayed,
so they have their trauma and
then later they start bleeding
especially with the joints.
So the long term complication
that’s really debilitating
for these patients is the
It turns out blood is
very irritating to joints
and it causes degradation
of that joint
and these patients end up
with very severe arthritis.
They also can occasionally get infection
from transfused blood products.
There was a period of time when we
didn’t know how to screen for HIV
in the blood supply or we
didn’t know HIV existed yet.
And patients with hemophilia were
frequently getting those diagnosed with HIV
because of their transfusions.
So nowadays, transfusions are
very safe at United States
and blood is screened very effectively
for all kinds of disease.
However, there are still areas where
transfused blood isn’t screened for
all diseases and so these
patients may be at risk.
Patients overtime can develop
autoantibodies against recombinant factor
we’re using to treat them and we’ll
talk about treatment in a bit,
but we’re using
recombinant factor VIII.
And it is a human recombinant, but they
can nonetheless develop autoantibodies.
This is a devastating
thing to have happened.
These patients are at much greater
risk for severe bleeding events
because we are having difficulty transfusing
a medicine to which they’re allergic.
Because of the constant autoimmune
nature of this disease,
just demounting of autoimmune response
will result in things like delayed growth
and delayed sexual development.
So this is a real problem
if children develop
So how do we make the diagnosis?
If we suspect the
patient has hemophilia,
we will obtain a PT and PTT and we’ll
notice, “Oops, the PTT is prolonged”.
Remember that’s the intrinsic pathway
involving factors VIII and ix.
They should have a normal PT or INR.
So it’s not liver failure or some
other cause of prolonged bleeding.
When we get a platelet function assay,
we should and it should be normal
because now, we’ve ruled out for
example Von Willebrand’s disease.
Factor VIII and factor IX levels are
available and we can check plasma level
so we can distinguish whether
if this is hemophilia A or B
and that’s important for therapy.
If factor 8 is low, don’t forget to check
the Von Willebrand’s disease factor
as this could be Von
Okay, how do we treat
For severe patients, we’re going
to give them factor all the time
to maintain them at
a certain level.
However, for less severe patients
and really for all patients who
bleed and have a bleeding event,
we have to treat
So patients with hemophilia will come
in to be treated for acute bleeds
for which we give them recombinant factor.
The dose depends on the desired percentage
of factor that needs to be achieved
based on the weight of the child and
what percent you want to get to.
In what percent you want to get to
has to do with what the bleed is.
You probably don’t have to
memorize that for an exam,
but just to understand that it’s going to
vary depending on the severity of bleed
and how bad off the patient
is and how much they weigh.
Typically, for severe patients,
we will give primary prophylaxis.
So these are patients with, for instance,
less than 1% of their normal amount of factor
and these patients will get
typically between two and
three times per week doses
of recombinant factor.
The goal is to raise these severe
patients up to the 1% level,
which equivalent to
The reason why we don’t do this for
everyone, it is extremely expensive.
costs a lot of money
and so we have to be careful about
not giving it when it’s not needed.
Patients will often require transfusions
because they’re bleeding too much
and that’s generally
indicated for severe bleeds,
especially in patients with
So we don’t necessarily transfuse a
patient who has a low hemoglobin
if their vital signs are stable
and their bleeding is controlled.
But in an active bleed or a patient
with tachycardia, we need to transfuse.
Don’t forget, we usually have to transfuse
these patients if they’ve had severe bleeds.
If they have tachycardia or if they’re actively
bleeding, we must consider transfusion.
For a patient with a lowish hemoglobin
but who’s no longer actively bleeding
and their heart rate is okay,
we generally don’t transfuse.
So that’s my summary of
bleeding problems in children.
Thanks for your attention.