13. Myeloproliferative diaseases Ph-negative: polycythemia vera, essential thrombocytemia and primary myelofibrosis – pathogenesis, clinical manifestation, diagnosis, evolution, treatment.

Question 1

what are the different types of myeloproliefrative diseases ? and how can we differentiate them from CML

Answer 1

CML - the only philadelphia chromosome positive

myeloproliferative diseases are of the elderly unlike hodgkin and agressive non hodgkin lymphoma

Question 2

why does myelocproliferative disease have attacks of gout ?

Answer 2

rapid cell turnovers - purine metabolism - increase in uric acid

Question 3

what is a feature of PV , ET AND CML ?

Answer 3

they can all covert into each other and go to myelofibrosis

and acute myeloid leukemias

and uric acid = gout attack

Question 4

what are all the different types of polycethmia vera

Answer 4

relative = where the plasma in the blood is low

there is absolute :
primary = mutation = cancer

secondary
compensatory
hypoxia = copd , obstructive sleep apnea , high altitude , cyanotic heart disease
increase EPO

or abnormal
tumor in the kidney secreting EPO = RCC AND HCC

Question 5

what is the complication of polycethmia vera ?

Answer 5

BUDD CHIARI SYNDROME
hepatic vein congestion

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myocardial infraction
ischemic stroke

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malignant transformation = myelofibrosisi and acute myeloid leukemias

Question 6

what is the clinical presentation of polycethmia vera ?

Answer 6

bruising and bleeding = lots of platelets which are not functioning properly

hot shower AQUATIC PRURITIS

erythromelalgia = redness and swelling , burning pain in the extremities
= use aspirin
= use calling and blood elevation

gout

heaptosplenomegaly

hyperviscocity syndrome

tortuous retinal veins
- visual disturbances

• neurological
  headache , vseizures and coma

spontaneous bleeding

thrombosis = use aspirin

Question 7

how do we diagnose polycethmia vera ?

Answer 7

2 major and one 1 minor
or 2 minor and 1 major

major

CBC
hemoglobin more than 18.5g/dl and 16.5 in women

JAK 2 MUTATION GENETIC TESTING

minor
bone marrow hypercellularity
tri lineage growth or red blood cells , white blood cells and platelets = PANMYELOSIS
absence of bone marrow iron because it is all used out

serum EPO is low

endogenous erythroid colony formation

hematocrit more than 48 percent

radiology to rule out EPO neoplasia

arterial blood gas
no hypoxia

Question 8

treatment of polycethmia vera ?

Answer 8

phlebotomy

myelosuppresant - hydroxyurea

apririn = erythromelalgia and thrombosis

anihistamine for aquagenic prurutis

allopurinol and rasburicase = decrease uric acid

Question 9

IN PRIMARY MYELOFIBROSISI , polycethemia vera and essential thrombcytosis what is the genetic problem ?

Answer 9

JAK 2 kinase activation = but in primary myelofibrosisi it is only found in some patients

Question 10

how can we diagnose essential thrombocytosis ?

Answer 10

genetic test for jak 2

CBC

WBC AND hematocrit are NOT markedly elevated

increased thrombocytes more than 450,000 / ul

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peripheral blood smear = lots of platelets but they look morpholically different

many large platlets = megakaryocytic and immature platelets from the bone marrow

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bone marrow biopsy = hypercellularity
megakrocyte hypertrophy and hyperplasia

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exclude all causes of secondary thrombocytosis - infection , inflammation , iron def anemia , trauma

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bleeding time is prolonged
however PT , PTT (partial thromboplastin time) normal because normal coagulation factors
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decreased TPO

Question 11

what is the complication of essential thrombocytopenia ?

Answer 11

increase risk for thrombosis

increased risk of bleeding

= hemorrhagic thrombocytosisi

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HEPRVISCOC ITY SYNDROME AGAIN

Question 12

what is the clinical presentation essential thrombocytosisi ?

Answer 12

brusing
spontaneous bleeding
erythromelagia

NO HEPATOSPLENOMEGALY!!

Question 13

treatment of essential thrombocytosisi ?

Answer 13

aspirin = for erythromyalgia and antiplatelet and thrombosis

hydroxyurea = cytoreductive

= anagrelid = reduce thrombocytes
stop megakaryocytic to mature into thrombocytes

Question 14

what is the clinical presentation of myelofibrosis

Answer 14

there are two phases

prefibrotic hyperceullar phase
=asymtopmatic
hepatosplenomegaly

hyperviscocity syndrome

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and fibrotic phase
=ANEMIA INCREASES AND SYMPTOMS OF FATUGUE , DYSPNEA AND ANGINA PECTORIS STARIN
pallor

leukopnea - infections

Question 15

diagnosis of primary myelofibrosisi ?

Answer 15

leukocytosis and thrombocytosis and red blood cells pan myelosisi

hyperplasia of atypical megakaryocytes = leading to increased moclonal proliferation of fibroblasts

however bizarre looking platelets in peripheral blood smear

immature nucleated red blood cells
pro myelocytes
myeloblasts

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in later pancytopenia

tumor of thespleen

anemia with anisocytosis
(RBC different forms) and poikilocytosis (not round).

CHARECHTERISTIC
leukoerythroblastosis = tear drop erythrocyte = peripheral blood smear

dry tap in bone marrow aspirations

x ray = osteoscloerisis

Question 16

treatment of primary myelofibrosis ?

Answer 16

enlargement of the spleen or spleen tumors remove the spleen

steroid - inhibit fibroblasts

allopurinol for gout

symptomatic anemia - epo

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chemo
low dose thalidomide and predinose (for multiple myeloma aswell)

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definitive therapy is allogenic bone marrow transplant