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Chronic myeloproliferative disorders
-This handout is only lecture based ,on the general and most important principles
to approach a patient with myeloproliferative disorder .
-Myeloproliferative disorders : hyperproliferation of neoplastic myeloid
progenitors that retain the capacity for terminal differentiation , as a
result ,there is an increase in one or more formed element in the peripheral
blood, the neoplastic progenitors tend to seed secondary hematopoietic
organs (the spleen,liver and lymph nodes) resulting in splenomegaly .
The multipotentialhematopoietic stem cells in the bone marrow gives rise to
2 progenitors :
1 – Lymphoid
2-Myeloid(‫(نقي العظم‬, which gives rise to 3 cell lines :
-RBCs : primary increase Polycythemiarubravera
-Platlets: primary increase  Essential thrompocythemia
-WBCs(include :monocytes and macrophages, neutrophils, basophils,
eosinophils): primary increase  Chronic myelogenous leukemia
*Features ofmyeloprolifrativedisorders ?
1-All patients with myeloprolifrative disorders have
SPLENOMEGALLY(spleen becomes palpable when it enlarges 3 times normal,
all of them have spleenomegally,but not all have plapable spleen)
2-Termination to Acute Leukemia(more than 20% of the bone marrow cells
are BLASTS)
3-Always check the differential count of WBCs ,basophils and eosinophil
increase means myeloprolifrativedirorders.
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3-Execlude secondary causes (always remember to execlude secondary
causes for the increment)
EssentialThrombocythemia(ET)
-CBC :High platlets count , increased basophils and/or esinophils
-Clinical presentation :
Hyperviscosity:manifestedby:a)Thrombosis : Arterial> CVA ,Venous >DVT ,
portal vein thrombosis b)dizziness c)Infarction ,Tenatus? (most ES patients
in Jordan present with),Erythromelalgia :painful big toe specially in hot
weather
-Hyperviscosity syndrome can be due to increased RBCs count (polycythemia)
, increased WBCs count (CML), increased platelets count (ET)
,Paraproteinemia
-Exclude secondary causes :Increased platelets count(thrombocytosis) :
splenectomy , bleeding , reactive (inflammatory , infection , cancer,
lymphoma , iron deficiency anemia )
-Check for Splenomegaly
-Make a Blood film (Megacariocites and numerous different size platelets )
-Take a bone marrow biopsy and check for thecytogenetics
-Management : Aspirin , and medications to lower plateletscount>Hydoxiurea
, and we sometimes use Thrombopheresis(an attempt to take thrombocyte
and restore other blood component to subject)
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Polycythemia Rubra Vera:
-CBC : increased hematocrit, other cell lines can be increased , remember to
check for esinophila/basophilia which confirm myeloprolifrative disorder
-Exclude secondary causes of Increased Hematocrit(secondary
polycythemia, note that cyanosis is a hallmark of secondary polycythemia) :
reactive (infection , inflammatory) , smoking , hypoxia(COPD,cyanotic
congenital heart disease) Always check O2 saturation,PO2, low in secondary
polycythemia and normal in polycythemia rubravera) , Androgens intake,
Renal cell carcinoma (increase erythropoietin ,while in primary polycythemia
erythropoietin will be decreased by negative feedback) ,Relative
polycythemia : reduced plasma volume , dehydration as in diuretics(check if
the patient is on diuretics)
-Remember that polycythemia can be masked by iron deficiency anemia, so
always check for Hematocrit not Hemoglobin
-When do we say this person has polycythemia ?
Check Hematocrit : Males Hct : > 51 % , Females : > 48%
-Check for splenomegaly
-Cytogenetics : JAK2 mutations is positive in polycythemia vera
Clinical presentation:headache ,hyperviscosity syndrome-thrombosis , itching
and it can terminate to AML
-Management :Venesection phlebotomy (remember that we don’t do
phlebotomy for patients with secondary polycythemia due to hypoxia
“physiological polycythemia”) , target Hct : Males < 45 % , Females : < 42 %
(to avoid thrombosis)
Chronic myeloid Leukaemia (CML)
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-CBC :autonomous growth of cell lines(can present with increased count of all
cell lines) , increased WBCs count (low lymphocytes count (5-10%) ,and high
neutrophils) ,remember to check for eosinophila/basophilia which
confirmmyeloproliferative disorder
***Normal Eosinophils count : (1-3 %) , Basophils : (0-0.75 %)
-Exclude secondary causes for leukocytosis : reactive leukomoid reaction
(infection,chronicinflammation,stress,certain nepplasms) ,WBCs infections
usually don’t exceed 50,000 ,in CML it’s above 100,000 with
eosinophilia/basophilia
-Check for splenomegaly
-Clinical presentation :hyperviscosity syndrome(thrombosis, headache) , low
grade fever , weight loss , fatigue , abdominal discomfort and early satiety
from massive splenomegaly , bone pain from infiltration with WBCs)
-Remember that all myeloprolifrative disorders are associated with
splenomegaly ,CML and Myelofibrosis cause massive palpable splenomegaly ,
while polycythemia vera and essential thrompocythemia cause mild to
moderate splenomegaly (checked by ultrasound)
-Blood film : manual differential :
Stages of maturation :
Blasts promyelocytsmyelocytsmetamyelocytesband neutrophils (all
are present in the blood film+eosinophils/basophils) = CML
-Bone marrow biopsy: < 5 % blasts (chronic phase) , most patients present in
the chronic phase, can transform for AML (accelerated phase)with bone
marrow blasts >20%
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-Cytogenetics : positive Philadelphia chromosome t(9,22) (bcr-abl gene
transformation ) (when there is overlap of increased hematocrit /platelets
count and WBCs we make cytogenetics for Philadelphia chromosome to
confirm CML)
-Remember that in AML :low Hematocrit and platelets because there will be
bone marrow infiltration with the blasts so it will stop producing other cell
lines.
-Management :Imatinib (protein kinase inhibitor)
Myelofibrosis
-CBC: early phase increase in cell lines , late phase decrease in Hb and
platelets
-Check for splenomegaly ( massive in myelofibrosis)
-Blood film :leukoerythroplastic blood film (bone marrow stress manifested
by nucleated RBCs and early blasts) ,characteristic tear drop RBCs
-Bone marrow biopsy :Replacement of bone marrow by fibrosis.
-Dry aspirate when aspiring the bone marrow the aspirate will be dry
Management : bad prognosis , untreatable , anti-JAK2 mutation has been
implicated recently, splenectomy (Extramedullaryhematopiosis might also
result in hepatomegaly)
**Special Greetings to the AWESOME B10 :D , GoodLuck everyone 
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