myeloproliferative disorders

Question 1

what is a myeloproliferative disease

Answer 1

monoclonal proliferation of myeloid precursors

Question 2

how do myeoproliferative disorders differ from acute leukaemia

Answer 2

MPD still have ability to mature - lots of abnormal mature cells
acute leukaemia - proliferation of precursors that don’t mature - lots of blasts in peripheral blood

Question 3

what are the 4 MPDs

Answer 3

polycythaemia rubra vera (red cells)
essential thrombocythaemia (platelets)
idiopathic myelofibrosis
chronic myeloid leukaemia (white cells)

Question 4

what MPD is BCR-ABL1 positive and why

Answer 4

CML - Philadelphia chromosome produces BCR-ABL1 protein

Question 5

what is Philadelphia chromosome

Answer 5

9:22 translocation

Question 6

what is BCR-ABL1

Answer 6

tyrosine kinase

Question 7

course of CML

Answer 7

chronic phase - few if any symptoms
accelerated phase - increasingly worse
blast transformation - acute leukaemia and death (acquired maturation defect)

Question 8

presentation of CML

Answer 8

B symptoms - weight loss, night sweats, fever
fatigue
gout
bleeding
abdo pain

Question 9

what are symptoms common to the MPDs

Answer 9

increased cell turnover - gout, fatigue, weight loss, sweats
splenomegaly - abdo pain, early satiety
marrow failure - fibrosis, other lineages affected
hyperviscosity - thrombosis

Question 10

blood count in CML

Answer 10

increased WBC (neutrophils, eosinophils, basophils)
low Hb (bone marrow failure)
platelets variable 
high urate and B12

Question 11

if high WCC, why is patient immunosuppressed

Answer 11

these white cells are abnormal

Question 12

bone marrow aspirate in CML

Answer 12

hypercellular

Question 13

what treatment can be given for CML

Answer 13

tyrosine kinase inhibitors (imatinib) if Philadelphia chromosome is present
fatal without bone marrow transplant in chronic stage

Question 14

what are secondary causes of polycythaemia

Answer 14

chronic hypoxia (COPD, smoking, EPO tumour)
dehydration, diuretics, obesity

Question 15

what constitutes polycythaemia rubra vera (true polycythaemia)

Answer 15

high Hb/haematocrit with erythrocytosis (increase in red cell mass)

Question 16

presentation of PRV

Answer 16

headache
aquagenic itch
plethoric appearance

Question 17

what investigations should be done in suspected PRV

Answer 17

rule out secondary causes - screen for COPD, smoking, diuretics
FBC - high Hb, high haematocrit, may have increased WBC/platelets
bone marrow aspirate - hypercellular with erythroid hyperplasia
low serum EPO
normal PaO2
increased red cell mass on Cr15 labelling

Question 18

what genetic mutation is often present in PRV and what does it cause

Answer 18

JAK2 - cells don’t require EPO

Question 19

treatment of PCV

Answer 19

vensect to haematocrit <0.45 (young patients)
aspirin
cytotoxic oral chemotherapy (old patients) -hydroxycarbamine

Question 20

what is essential thrombocythaemia

Answer 20

proliferation of megakaryocytes leading to increased abnormal function
platelets >1000

Question 21

presentation of ET

Answer 21

vasoocclusive symptoms - thrombosis 
bleeding - platelets are not functioning (surgery)
headache 
chest pain
light headed

Question 22

what are causes of reactive thrombocytosis

Answer 22

blood loss
inflammation 
malignancy
iron deficiency
RULE THESE OUT

Question 23

what genetic mutations might be present in ET

Answer 23

Jak2
CALR
MPL

Question 24

bone marrow aspirate in ET

Answer 24

clusters of megakaryocytes

Question 25

treatment for ET

Answer 25

aspirin

if >60 give hydroxycarbamide

Question 26

what is myelofibrosis

Answer 26

hyperplasia of megakaryocytes which produce platelet
derived growth factor
leads to marrow fibrosis and myeloid metaplasia

Question 27

when is it common to get myelofibrosis

Answer 27

post-PRV or ET

can be idiopathic

Question 28

presentation of myelofibrosis

Answer 28

marrow failure and fibrosis (anaemia, low platelets, low WBC)
extramedullary haematopoiesis (hepatosplenomegaly - early satiety, LUQ pain, portal hypertension)

Question 29

diagnosis of MPD

Answer 29

blood film - tear-drop shaped RBC and leucoerythroblastic
fibrosis on bone marrow biopsy
JAK2 or CALR mutation

Question 30

why do red cells appear tear-dropp shaped in myelofibrosis

Answer 30

trying to squeeze out of fibrosed marrow - deforms them

Question 31

MF treatment

Answer 31

blood transfusions 
platelets
antibiotics 
bone marrow transplant in young people
splenectomy?
JAK2 inhibitors