Myeloproliferative Disorders

Question 1

What cells are of the myeloid lineage?

Answer 1

granulocytes (eosinophils, neutrophils, basophils)
red blood cells
platelets

Question 2

How do the myeloproliferative disorders differ from leukaemia?

Answer 2

maturation is preserved - they retain ability to differentiate into red blood cells, platelets and granulocytes

Question 3

What are the disorder subtypes?

Answer 3

BCR-ABL1 positive

BCR-ABL1 negative

Question 4

What are the BCR-ABL1 positive myeloproliferative disorders?

Answer 4

chronic myeloid leukaemia

Question 5

What are the BCR-ABL1 negative myeloproliferative disorders?

Answer 5

polycythaemia rubra vera
essential thrombocythaemia
idiopathic myelofibrosis

Question 6

What happens in chronic myeloid leukaemia?

Answer 6

overproduction of granulocytes

Question 7

What happens in polycythaemia rubra vera?

Answer 7

overproduction of red blood cells

Question 8

What happens in essential thrombocythaemia?

Answer 8

overproduction of platelets

Question 9

When should you consider a myeloproliferative disorder?

Answer 9

no reactive explanation
increased granulocyte count +/-
increased red blood cells/Hb +/-
increased platelet

Question 10

What is polycythaemia?

Answer 10

abnormally increased concentration of Hb in blood

Question 11

What are the 2 classifications of polycythaemia?

Answer 11

absolute - increased RBC mass

relative/pseudo - decreased plasma volume, normal RBC mass e.g. dehydration

Question 12

What are the causes of absolute polycythaemia?

Answer 12

primary: polycythaemia rubra vera (PRV)
secondary: hypoxia, inapprop. erythropoietin secretion e.g. renal carcinoma, hepatocellular carcinoma

Question 13

What mutation is found in >90% of people it PRV?

Answer 13

mutation in JAK2

loss of auto inhibition - activation of erythropoiesis in absence of ligand

Question 14

What should you distinguish PRV from when making your diagnosis?

Answer 14

secondary absolute polycythaemia

relative/psuedopolycythaemia

Question 15

What is increased in PRV?

Answer 15

increased Hb/ haematocrit

can have increased granulocytes and platelets

Question 16

What are the clinical features of PRV?

Answer 16

can be asymptomatic
hyper viscosity (headaches, dizziness, tinnitus, visual disturbance)
thrombosis (erythromelalgia, claudication, MI, TIA)
fatigue, itch, splenomegaly
gout (increased rate due to increased red cell turnover)

Question 17

What is erythromelalgia?

Answer 17

burning sensation in fingers and toes

Question 18

In PRV, what does increased proliferation of red blood cells, granulocytes and platelets cause?

Answer 18

hyper viscosity

thrombosis

Question 19

What are the investigations for PRV??

Answer 19

JAK2 mutation
FBC (increased Hb, increased haemotocrit, increased PCV, also can have increased WCC, platelets)
exam - splenomegaly?
bone marrow - erythroid hyperplasia

Question 20

What is the treatment of PRV?

Answer 20

venesection to keep haematocrit <0.45 (to prevent thrombosis)
cytotoxic chemo e.g. hydroxycarbamide
low dose aspirin

Question 21

What is essential thrombocythaemia?

Answer 21

clonal proliferation of megakaryocytes

uncontrolled production of abnormal platelets

Question 22

What does the high level of abnormal platelets cause in essential thrombocythaemia?

Answer 22

bleeding or arterial/venous thrombosis and microvascular occlusion

Question 23

What are the clinical features of essential thrombocythaemia?

Answer 23

headache, atypical chest pain
thrombosis, erthyromelalgia
splenomegaly
light headed, fatigue, wt loss

Question 24

How is essential thrombocythaemia diagnosed?

Answer 24

rule out other causes of thrombocytosis (increased platelets) e.g. infection, bleeding, malignancy, inflammation, trauma
exclude CML
bone marrow

Question 25

What is the treatment of essential thrombocythaemia?

Answer 25

low dose aspirin

hydroxycarbimide to reduce proliferation (if older, previous thrombosis)

Question 26

What is idiopathic myelofibrosis?

Answer 26

hyperplasia of megakaryocytes - produce platelet-derived growth factor –> marrow fibrosis (leading to marrow failure)
extra medullary haematopoeisis –> hepatosplenomegaly

Question 27

What are the clinical features of idiopathic myelofibrosis?

Answer 27

marrow failure: anaemia, infection, bleeding
splenomegaly
thrombosis, headaches, gout

Question 28

How is idiopathic myelofibrosis diagnosed?

Answer 28

trephine biopsy - fibrosis

blood film: tear drop shaped RBC, leukoerythroblastic cells

Question 29

What is the treatment of idiopathic myelofibrosis?

Answer 29

marrow support (red cell transfusion, platelets, neutrophils)
allogeneic stem cell transplant - can be curative in young, high risk of mortality

Question 30

What is chronic myeloid leukaemia?

Answer 30

uncontrolled proliferation of myeloid cells

Question 31

What are the clinical features of CML?

Answer 31

features common with myeloproliferative disorders e.g. splenomegaly (abdominal discomfort), gout
weight loss, fever, fatigue, sweats
bleeding

Question 32

What is the Philadelphia chromosome?

Answer 32

present in CML
gene product - tyrosine kinase activity
results in new gene: BCR-ABL1

Question 33

How is CML diagnosed?

Answer 33

FBC: increased WCC (eosinophils, basophils, neutrophils), HB decreased or normal, platelets variable
bone marrow: hyper cellular

Question 34

What is the treatment of CML?

Answer 34

BCR ABL tyrosine kinase inhibitors e.g. imatinib