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Myeloproliferative
disorders
Done by: Dr. Mahmoud Ayesh
The Lecture was taken on
Tuesday 10\11\2009

Overview:
These make up a group of chronic
conditions characterized by clonal
proliferation of one or more
marrow cell linage Myelo- =
related to bone marrow.
It is important to determine if it is
clonal or not because if it isnt
clonal that means it is a reactive
process such as increasing RBC
in hypoxia, increasing WBC in
infections, and increasing platelets
in haemorrhage.
Remember that the most physical
sign in all myeloproliferative
disorders is the splenomegaly.

The patient usually comes with


abdominal distension, because the
spleen compresses the lung, and if
you look to the CBC you will notice
that WBC will be high, HB normal
and platelets normal. But if you
look to the CBC of patient of AML
you will notice high WBC, low
platelet and HB, and in BM there
is >20% blast cells.
So, when we say Myeloproliferative
disorders this means that there is any
elevation in WBC, RBC, and platelets or one of
them at least with splenomegaly.

1. Chronic Myeloid leukaemia CML


Is a Myeloproliferative disorder
characterized
by
increased
proliferation of all haematopoietic
lineages
but
manifesting
predominantly in the granulocytic
cell line, without the loss of their
capacity to differentiate.
Consequently, the peripheral
blood cell profile shows an
increased number of granulocytes
and their immature precursors,
including occasional blast cells.
 On blood film: all stages of maturations
from blast to neutrophil & majority of
cells are myelocytes & neutrophils

These disorders include:


1. Chronic myeloid leukaemia CML in
WBC.
2. polycythemia rudra vera PRV in RBC.
3. if occur in platelets; Essential
(Primary) Thrombocythemia
4. Myelofibrosis

These disorders have possibility to


progression from one to another
e.g. PRV to Myelofibrosis, and may
be terminate to AML.
Page 1 of 9

CML refers to a condition where the cells


look mature but they are not really normal.
We distinguish CLL from it by lymphocytes
which are the majority not the neutrophils.

The disease occurs chiefly


between the ages 30 to 80 with
average 55 years, more common
in males. The aetiology is
unknown.

 So, in CML the patients are Ph


chromosome and BCR ABL positive.

Clinical features:
Wt loss, lassitude, anorexia, night
sweats, Splenomegaly, Anaemia
pallor,
dyspnoea,
tachycardia
Bruising, epistaxis, menorrhagia,
Gout, renal impairment, and 25% of
patients are asymptomatic.
Case presentation:

Wt 3kgs

Normal c200gms

The patient, a 49yr old teacher, saw her


physician because of fatigue for about six
months. Physical exam Showed little
except for pallor, normal temperature, and
massive splenomegaly. Blood tests were
ordered to investigate possible anaemia.
Laboratory results indicated a high white
count consistent with Chronic Myeloid
Leukaemia.

 Remember, in CML the patients in there


CBC have high WBC, normal high or low
RBC and platelets, this is the difference
between CML and AML which has high
WBC with low platelets and HB.

Cytogenetic and molecular


aspects:
Approximately 95% of patients with
CML have
i.
A chromosome abnormality
known as the Philadelphia (Ph)
chromosome.
ii.
Reciprocal translocation
between chromosome 9 and 22
in region called BCR carried
ABL oncogene.

Page 2 of 9

Natural history:
The disease has three phases:
1) A chronic phase, most patients85%
diagnosed in chronic phase, characterized by
splenomegaly and leukocytosis with generally
few symptoms. This phase is easily controlled
by medication. The major goal of treatment
during this phase is to control symptoms and
complications
resulting
from
anemia,
thrombocytopenia,
leukocytosis,
and
splenomegaly. Newer forms of therapy aim at
delaying the onset of the accelerated or blastic
phase, duration3-4 years.

2)

An accelerated phase,

Characterized by
the emergence of a discrete blast cell population
and left-shift compared to chronic phase. But
the blast still less than 20%.

2. Essential Thrombocythemia (ET)


The malignant proliferation of
megakaryocytes Constitutive
production of thrombopoietin by
liver results in a raised level of
circulating platelets those are often
dysfunctional.
Prior to making a diagnosis of ET it
is essential to exclude reactive
causes of increase platelets.

3)

Blast phase,

defined as >30% blasts and


promyelocytes in peripheral blood or marrow.
Normal
marrow
erythropoiesis
and
megakaryopoiesis reduced. In this stage the
disease transformed into either AML 70% or
ALL 30.

Typical Blood Count


WBC x 109/L 10.0
[4-11]
Hb g/L 156
[140-180]
MCV fl 85
[80-100]
Platelets x 109/L 1560 [150-450]
Neuts x 109/L 7.0
[2-7.5]
Lymphs x 109/L 2.0
[1.5-4]
Monos x 109/L 0.8
[0.2-0.8]
Eos x 109/L
0.1
[0-0.7]
Basos x 109/L 0.1
[0-0.1]

 The platelets count should be > 600


*109\L at least two months.
Blood film
Many large and abnormal platelets
present:

Management
1. Curative treatment: by allogeneic
2.

bone marrow transplant, but it is still


not completely curable.
Control treatment: by Imatinib
which inhibit BCR-ABL activity but it is
very expensive 3000 JD\month, or by
hydroxyurea and interferon.

Page 3 of 9

Clinical features:
In this disease the platelets become as a
clusters which leads to thrombosis, so
the patient come with erythromelagia
painful big toe, CVA such as TIA or
stroke, or he may come with bleeding.

Management
Aspirin useful to reduce the risk of
thrombosis, also we can use hydroxyurea.

3. Polycythemia Rubra Vera (PRV)


A neoplastic (clonal) stem cell
disorder,
leads
to
excessive
production of all myeloid cell lines,
predominantly red cells.

Clinical features
The increase in whole blood
viscosity causes vascular occlusion
and ischemia, compounded by the
increase in platelets.
Headaches, Itch, Thrombosis, TIA,
stroke, and Splenomegaly are also
finding.

Diagnosis
1) The most important thing is to
distinguish it from secondary
PRV, e.g.


Hypoxia due to chronic lung diseases,


or congenital heart disease VSD
In renal cell carcinoma which leads to
increase erythropoietin synthesis,
Reduction in the plasma volume due
to diuretics therapy, so we should
notice that the plasma volume is
normal while the PCV is high,
And in the smokers

2)

Red cell mass: Raised packed cell




volume (PCV) in Males PCV>51%


and in Females PCV >48%.
3)

O2 saturation must be >92%

4)

Normal or low erythropoietin

5)

Splenomegaly and central cyanosis

6)

Normal plasma volume level

Page 4 of 9

Typical blood count


WBC x 109/L
Hb g/L
HCt
MCV fl
Platelets x 109/L

18.0
200
0.62
75
850

[4-11]
[140-180]
[.42-.51]
[80-100]
[150-450]

Neuts x 109/L
Lymphs x 109/L
Monos x 109/L
Eos x 109/L
Basos x 109/L

14.6
2.0
0.8
0.1
0.5

[2-7.5]
[1.5-4]
[0.2-0.8]
[0-0.7]
[0-0.1]

 Some patients come with HB 140, low MCV


high RBC 7-8 million and the HCt 50,
those patients have PRV masked by iron
deficiency anaemia.
Management
1) Phlebotomy venesection to
decrease viscosity, repeated every
5-7 days till hematocrit become
less than 0.45
2) low-dose aspirin (controversial) 80 mg/day
3) hydroxyurea if necessary
4) do not treat with iron

4. Myelofibrosis (MF)
Is characterized by bone marrow
fibrosis, extramedullay haematopoiesis
blood cell formation outside the bone marrow and
a leukoerythroblastic blood picture.

Typical blood count


 bone marrow failure
WBC x 109/L 2.4
Hb g/L
88
MCV fl
85
Platelets x 109/L
Neuts x 109/L 1.0
Lymphs x 109/L
Monos x 109/L
Eos x 109/L
Basos x 109/L

[4-11]
[140-180]
[80-100]
60[150-450]
[2-7.5]
1.0
[1.5-4]
0.2
[0.2-0.8]
0.1
[0-0.7]
0.1
[0-0.1]

Blood film:
A few nucleated red cells,
myelocytes (leukoerythroblastic).
Tear-drop poikilocytes.

1) What is your diagnosis?


2) What are the clinical
presentations or other
complication can be happen?
3) What you can find on physical
examination of abdomen?
Answers:
1) Primary: Essential thrombocytothemia
Secondary: Chronic Myeloid Leukaemia,
post splenectomy, malignancy,
inflammatory diseases (eg.rhumatoid),
bleeding, anaemia
2) Essential thrombocytothemia because
many large and abnormal platelets are
present in blood film.

Past Mini-OSCE Questions


Case 1:
50 year female patient presented to ER
complaining of painful big toethis is
a CBC for her:
WBC x 109/L
10.0
Hb g/L
156
MCV fl
85
Platelets x 109/L 1560
Neuts x 109/L
7.0
Lymphs x 109/L 2.0
Monos x 109/L 0.8
Eos x 109/L
0.1
Basos x 109/L 0.1

[4-11]
[140-180]
[80-100]
[150-450]
[2-7.5]
[1.5-4]
[0.2-0.8]
[0-0.7]
[0-0.1]

3) Erythromelagia, Peripheral Vascular


Occlusion, Transient Ischemic Attack
(TIA), Stroke, Bleeding (esp. surgical)
4) Splenomegaly

Case2:
63 smoker male patient presented to a
clinic complaining of headache, & this
is a CBC for him:

1) What is your differential


diagnosis?

WBC x 109/L
Hb g/L
HCt
MCV fl
Platelets x 109/L
Neuts x 109/L
Lymphs x 109/L
Monos x 109/L
Eos x 109/L
Basos x 109/L

Then we do this blood film for her


picture above

1) What is your differential


diagnosis?

Page 5 of 9

18.0
200
0.62
75
850
14.6
2.0
0.8
0.1
0.5

[4-11]
[140-180]
[.42-.51]
[80-100]
[150-450]
[2-7.5]
[1.5-4]
[0.2-0.8]
[0-0.7]
[0-0.1]

2) What is your physical examination &


investigations to confirm your
diagnosis?
If you know that the patient has
splenomegaly & normal cardiac &
respiratory system & packed cell volume
(PCV) is 70%, Oxygen saturation is 97%
Erythropoietin is 3 mUnits/ml decreased
Normal plasma volume.

3) What is your diagnosis?


4) What are the clinical features can
be happen?
Answers:
1) Primary: Polycythemia (Rubra) Vera
Secondary: smoking, COPD, diuretics,
cyanotic heart disease, poly cystic kidney
disease, renal cell carcinoma.
2) PCV, oxygen saturation, plasma
volume, erythropoietin level,
ultrasound for spleen ,liver & kidney
3) Polycythemia (Rubra) Vera (PRV),
4) Headaches, Itch particularly after a
hot bath Vascular occlusion
Thrombosis in unusual sites TIA,
stroke Splenomegaly

Case 3:
70 year male patient presented to you
has massive splenomegaly, history of
pallor with malaise..this is a CBC
for him:
WBC x 109/L
Hb g/L
MCV fl
Platelets x 109/L
Neuts x 109/L
Lymphs x 109/L
Monos x 109/L
Eos x 109/L
Basos x 109/L

2.4
88
85
60
1.0
1.0
0.2
0.1
0.1

[4-11]
[140-180]
[80-100]
[150-450]
[2-7.5]
[1.5-4]
[0.2-0.8]
[0-0.7]
[0-0.1]

1) What is your differential


diagnosis?
When you do a blood film it is look
like this:
Picture Above

Page 6 of 9

2) Describe what you see on these


blood films?
3) What is your diagnosis?
4) How body will compensate?
Answers:
1) leukaemia, lymphoma ,TB , radiation ,
chronic infections, glaucomatous
disorders, metastatic cancer,
autoimmune disorders Myelofibrosis
2) Pic 1: tear-drop cell which is
pathognomic.
Pic 2: Leukoerythroblastic blood film
3) Myelofibrosis
4) Subsequent marked increase in extra
medullary haematopoiesis (primarily
in the liver and spleen, which enlarge
significantly).

Case 4:
About chronic myeloid leukaemia
these pictures from web path, because there is no
picture about this in slide.

Remember:
Increased WBCs
Normal or high RBCs
Increased platlets
With basophilia & eosinophilia

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Diagnosed by CBC, splenomegaly, BM


Imp. Remember: Philadelphia chromosome t(9:22) &
BCR-ABL gene

The end
Done by: Hashem Yassin
www.shifa2006.com
On facebook:
2012 J2009
 
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