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Course: Health and medicine > Unit 6
Lesson 8: Myeloproliferative disordersWhat is primary myelofibrosis?
Learn what is primary myelofibrosis as well as how to identify its signs and symptoms, diagnose it, and treat it. By Raja Narayan. Visit us (http://www.khanacademy.org/science/healthcare-and-medicine) for health and medicine content or (http://www.khanacademy.org/test-prep/mcat) for MCAT related content. These videos do not provide medical advice and are for informational purposes only. The videos are not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of a qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read or seen in any Khan Academy video. Created by Raja Narayan.
Want to join the conversation?
- He said that there was only one cure but he just listed three. Are the other two something extra people do or are they actual cures?(3 votes)
- The transfusion and splenectomy are temporary solutions while the stem cell transplant is a permanent fix/cure.(2 votes)
- How is this then a myelo'proliferative' disorder?? Is it just because of the JAK-2 mutation?(2 votes)
- It's because at the base level, the disorder originates from cell production in the myeloid tissue. Either there is too much, too little, or the product is bad.(2 votes)
- is there any less intervening testing on bone marrow other than marrow biopsy or aspiration(2 votes)
- I have listened to all of the Myelopriferative Neoplasm section. For MF and PV there is no mention of JAK inhibitors as a treatment option. There is no mention of clinical trials as a treatment option for any of these cancers. Why?(2 votes)
- At1:58, Can bone marrow be made in Liver?(2 votes)
Video transcript
- Primary Myelofibrosis is
a disorder where you have connective tissue and fibroblasts,
that's what fibrosis is, so connective tissue or
fibroblasts being produced in the bone marrow,
that's what myelo means. Now primary myelofibrosis means that this happens on its own, because there are other
types of myelofibrosis associated with the other
myeloproliferative disorders. So that means that primary
myelofibrosis is a disorder wherein the the shaft of
long bones like the femur or other places in your
body you make bone marrow, remember these sites are
important to make cells like this pluripotent,
meaning having the ability or the potency to make
many or plural things, hematopoietic, meaning related
to the blood, stem cell. So this is a pluripotent
hematopoietic stem cell. It has the ability to
make a variety of cells we find in the bloodstream. So here I'm just drawing out
the lymphoid stem cell lineage up here is the myeloid stem cell lineage we're going to talk about in more detail, while the issue in primary
myelofibrosis is that the marrow in the femur
is just replaced with connective tissue, making
it difficult to produce these pluripotent hematopoietic stem cells or the myeloid stem cells and
eventually red blood cells white blood cells or even platelets. You've just got a dry bone marrow. You don't have the blood
cell-producing apparatus you need. So one thing that might come
to mind is that if we're not making these stem
cells in the bone marrow, well where do we make it instead? And the explanation is
that primary myelofibrosis often occurs with what's
called myeloid metaplasia, which you might recall myeloid means related to the bone
marrow and then metaplasia in this instance indicating
that the bone marrow is made elsewhere, and
that elsewhere in fact will be in your liver, will become bigger, that's why I drew it like this, so it can accommodate the extra function of producing hematopoietic stem cells. Your spleen develops
the same sort of role, it'll also grow bigger
like this to accommodate the extra function of producing stem cells for the blood cells we
have in our vasculature. And this can all be traced back, this fibrosis in the bone right here, to a JAK2 kinase mutation. Now this should be a
familiar buzzword to you, because this is the exact
same mutation you have in polycythemia vera and in
essential thrombocythemia. But the main difference is
that the defect will happen very early on, here in the bone marrow, which then compromises the
production of other cells that should come off of
these stem cells later on. And I'll draw them out
right here for completeness, so we can reference them
in our conversation. So the important thing to realize is that the cells that we
are supposed to be producing here from our bone marrow
because they're not being made, cause us to have signs
and symptoms associated with their deficiency, or their absence, and this will produce
certain characteristic signs and symptoms such
as abdominal fullness, which I think we already alluded to, which is associated with
the growth in your spleen, which is turning it into a mega-spleen, or we call this situation splenomegaly, and when this happens
in the liver as well, giving you hepatomegaly, you have in total what's referred to as hepatosplenomegaly. So hepatosplenomegaly. You can also get bone pain, because rapid fibrosis
in the bone marrow will impinge on the nerves there. And then beyond that we
can start to think about what happens when we're lacking the cells we should be making in the bone marrow. For instance when we don't have platelets which should be clotting when we have cuts to our blood vessel, we end up
having unregulated bleeding, which could manifest as
either having nosebleeds, or what are called ecchymosis, ecchymosis which is just
a fancy term for bruises. And these will happen when you bump, let's say you're walking in crowded room and you bump your thigh
into a table or a chair, even a slight knock can
produce a very serious bruise when you're deficient in platelets. Now when you're deficient
in in red blood cells you can start to look paler,
so you'd have some pallor, or, because you don't have
enough red blood cells to get oxygen throughout your body, perhaps you'll have
some dizziness as well. And again, this is due to
having decreased number of red blood cells, and
then the bleeding is due to a decreased number of platelets. And then finally with a decreased number of white blood cells, you
can develop what are called opportunistic infection, because the low white
blood cell count you have makes you relatively immunosuppressed, giving infectious organisms
like bacteria and viruses the opportunity to attack. Now, how do we diagnose this? Well one of the first
things you can do is get a complete blood cell
count and you'll notice that you have a decreased number of red blood cells and platelets. You may also have an increased number or immature white blood cells. Another thing you can
do is look at your blood in a microscope, that's called
a peripheral blood smear, and that'll show red blood
cells with an unusual shape. They'll look like teardrops, as you can see in this image here. Now while we might have some
relatively normal-looking red blood cells like this,
you've got these teardrop-shaped red blood cells that
indicate that these cells are passing through a
fibrotic bone marrow, which causes them to shear
and have this unusual shape. So let's minimize this. And then moving on, sort of
the last two things you can do, is look directly at the bone marrow. You can do a bone marrow aspirate, meaning try and draw up
some of the bone marrow with a big needle, and notice
that you don't get much, we say this is a dry tap,
or the bone marrow is dry. And that indicates that we're
not really producing things in the femur, because
we have fibrosis there. And then at that point some
people might elect to do what's called a bone marrow biopsy, which means instead of
taking a large needle to suck up some of the bone marrow, you go in and take out a chunk
using a big needle as well. And by doing this biopsy
you can see some fibrosis. Okay. Now what can we do to
treat primary myelofibrosis with this myeloid metaplasia? Well, fortunately there's one cure, and that is to replace
the fibrosis that's there with other stem cells. And so you'd have to do what's called a stem cell transplantation. Sometimes while we wait
for the opportunity to do a stem cell transplantation, patients may be given a transfusion of blood cells that they're missing to increase their red blood cell count, or even their platelet count. And finally one of the
other things we can do that I guess I should mention here, because primary myelofibrosis
with myeloid metaplasia is actually the most common
cause of splenomegaly in anyone above age 50 years old. The last thing we can do is
what's called a splenectomy, because if the spleen gets so big that it's impinging on vessels, and causing too much abdominal fullness where the patient is so
uncomfortable and in pain, we'll have to get rid of it. Now primary myelofibrosis is
a pretty uncommon disease, with some very interesting
pathophysiology, and it all goes back to thinking about what are the functions of these cells, and when we don't have
them, what ends up happening to give us certain signs and symptoms, and then what do we need to look for, to really indicate that
this is the issue we have here in our bone marrow? And then what do we do to treat it?