In this lecture, we’ll discuss
bleeding disorders in children.
So we can think of bleeding disorders
based on how we know clots form.
First, there is tissue damage
and then both platelets and the coagulation
cascade occurs that help form that clot.
In children, there can be problems
with both the coagulation cascade
and platelet activation.
We’ll discuss platelet activation first.
So here’s an inherit cartoon
where you can see how
platelets activate together
and collide together
and there are 2 major
problems that can happen
with platelets that can lead
to platelet dysfunction.
One is problems with Von
and the other was intrinsic
problems within that platelet.
Let’s start with Von
So Von Willebrand disease is a genetic
defect in Von Willebrand factor.
It is the most common inherited
bleeding disorder in children.
We have to remember that Von Willebrand’s
factor does two different things.
First, it does bind the platelets,
but then also it acts as a
carrier protein for factor VIII.
So these patients may have
problems with factor VIII as well.
So there are many different types
of Von Willebrand’s disease
and I’d like to go through a few of them.
Some of them are important to understand
and some are so rare that we
can just discuss them briefly.
So type 1 is very common.
It’s the most common type
of Von Willebrand disease.
It’s autosomal dominant and it affects
about three-quarters of patients.
The severity of the disease can
vary a lot from mild to severe.
Type 2A is also autosomal dominant and
is present in about 15% of patients.
Usually they have moderate
degree of severity of illness.
The same thing can be said of type 2B,
again, autosomal dominant,
about 5% of patients
and again moderate
degree of illness.
And then there are the rare types.
There is the platelet-type
which is extremely rare,
but is a gain of
and these patients actually have
rather than a bleeding disorder.
Type 2M is fairly rare
and these patients have a normal
level of Von Willebrand’s factor
but it doesn’t work correctly.
Type 2N is autosomal recessive.
These patients have a low factor 8 level
and often, these patients are mistaken
for a patient with hemophilia.
And there's type 3 which
is extremely rare,
but these patients
are very sick,
they have a completely unmeasurable
amount of Von Willebrand’s factor
and resultingly a low
factor VIII as well.
So how do these patients present?
Well, they will present
absolutely with easy bruising,
bleeding, bleeding from the nose and
mouth and excessive menorrhagia.
So the easy bruising is
These bruises are usually large and
they’re often in unusual locations.
Sometimes, you might think that this child
might have been a victim of child abuse,
but in fact they have Von
They will often bleed excessively from
minor lacerations with prolonged bleeding
and they may get excessive
scarring of those lacerations.
Nose and mouth bleeding is common
and these patients usually
have frequent nose bleeds.
Often times, these nose bleeds are hard
to control and require afferent spray
and ice and all kinds of intervention
that most kids don’t require.
They also will bleed
excessively with tooth loss
or simply when they’re
brushing their teeth.
In terms of menorrhagia,
we usually pick this up in young girls
who are having their first period
and they will have dramatically
increased bleeding with their menses.
And the menses will
last longer than usual.
So if we wish to diagnose Von
Willebrand’s disease in a child
who is presenting with
we get a PT/PTT and in most
of these cases, it’s normal.
This is because their factor
VIII is working enough
that they have a normal
However, if we further investigate,
we will find that the platelet
function assay is prolonged.
The PFA or platelet function
assay has largely replaced
the bleeding time which
is also prolonged,
but we’re not using that
as often because it’s
harder to standardize on
For definitive testing, you can detect
levels of Von Willebrand’s factor antigen
and we can do something called
Ristocetin cofactor activity.
Ristocetin was an antibiotic
that they took off the market
because it caused
and the reason it did that is because
it bound to Von Willebrand’s factor.
So we can use this antibiotic
to determine how much
Von Willebrand’s factor is
present in patient’s serum.
The factor VIII level is obtained but
will be different in different patients
depending on the subtype of
disease as we discussed earlier.
So how do we treat Von Willebrand’s?
Well, we usually start
with a DDAVP challenge.
DDAVP increases Von Willebrand
factor and presence of factor VIII.
It’s not effective for
all subtypes of disease,
for example, type 3, it will
have not much effect at all,
but it is good for
types 1 and 2.
DDAVP is usually used
as a nasal spray.
Also, we have to watch for hyponatremia.
Remember, DDAVP causes insertion
of aquaporin channels
and causes reclaiming of free fluid, so
these patients may develop a low sodium.
Von Willebrand’s factor viii is usually
reserved for patients with very severe disease
and for a severe bleeding event,
we will usually give factor VIII as well
as recombinant Von Willebrand’s factor.
And we may use topical thrombin to mucous
membranes to help them stop the bleeding.
There are some other unusual
platelet aggregation problems
where the platelets have an inherit
problems sticking together.
The patient will have a
normal number of platelets,
they just won’t be
These patients tend to present
with severe bleeding disorders.
The normal number of
platelet is there.
They will have a normal Von Willebrand’s
factor and a normal PTT and PT.
So, it can be a challenge
to make this diagnosis
and a platelet function
assay is the way to do it.
When you think about this, remember
this is probably the most important
kind to remember for a test.