Myeloprolifertive Disorders

Question 1

What is the most common gene mutation in myeloproliferative disease?

Answer 1

JAK-2

Question 2

What is polycythaemia?

Answer 2

Increased in red cell count and PCV

Question 3

What is polycythaemia rubra vera?

Answer 3

Over-production of red cells
Increase in Hb and Hct
May have excessive production of other cells

Question 4

What is JAK2?

Answer 4

Tyrosine kinase

Question 5

How does polycythaemia rubra vera present?

Answer 5

Tiredness
Itching
Vertigo
Headache
Visual problems

Question 6

Which group tend to present with polycythaemia rubra vera?

Answer 6

> 60

Question 7

What may be common when a patient with polycythaemia rubra vera is hot?

Answer 7

Itching

Question 8

What are the major complications of PRV?

Answer 8

Haemorrhage

Thrombosis

Question 9

What may be found on examination of polycythaemia rubra vera?

Answer 9

Cyanosis
Splenomegaly
Hepatomegaly

Question 10

What is found on FBC in PRV?

Answer 10

High Hb

Question 11

What does bone marrow aspirate show in PRV?

Answer 11

Hypercellular

Question 12

How is PRV managed?

Answer 12

Venesection to get Hct <0.45
Low dose aspirin
Cytotoxic oral chemotherapy

Question 13

What is essential thrombocythaemia?

Answer 13

Overproduction of abnormal platelets

Question 14

How does essential thrombocythaemia present?

Answer 14

Usually with thrombosis

Erythromelalgia

Question 15

What is erythromelalagia?

Answer 15

severe burning pain, erythema and warmth at the extremities

Question 16

How is essential thrombocythaemia diagnosed?

Answer 16

Persistently high platelet count with no identifiable cause

Question 17

What may cause secondary polycythaemia?

Answer 17

Chronic hypoxia
Smoking
EPO-secreting tumour

Question 18

What may cause pseudopolycythaemia?

Answer 18

Dehydration
Diuretic therapy
obesity

Question 19

What is a psuedopolycythaemia?

Answer 19

When the plasma volume is reduction so the ratio seems high but the number of platelets is normal

Question 20

What does the JAK2 mutation cause in PRV?

Answer 20

loss of auto-inhibitions and activation of erythropoiesis in the absence of a ligand

Question 21

What cytotoxic chemo drug is given to treat PRV?

Answer 21

Hydroxycarbamide

Question 22

Why does essential thrombocythaemia present with bleeding sometimes?

Answer 22

Causes acquired vWF disease

Question 23

In which scenarios may a reactive thrombosis occur?

Answer 23

Blood loss
Inflammation
Malignancy
Iron def

Question 24

Which mutations may be present in essential thrombocythaemia?

Answer 24

JAK2
CALR
MPL

Question 25

What diagnosis should be excluded on suspicion of essential thrombocythaemia?

Answer 25

CML

Question 26

How is ET managed?

Answer 26

Anti-platelets Anagrelide Hydroxycarbamide Interferon alpha

Question 27

What is the action of anagrelide?

Answer 27

Inhibits megakaryocyte differention

Question 28

What is myelofibrosis?

Answer 28

Clonal proliferation of stem cells and abnormal myeloid cells

Question 29

What causes the fibrosis in myelofibrosis?

Answer 29

Hyperplasia of abnormal megakaryocytes which release fibroblast stimulating factors

Question 30

Give an example of a fibroblast stimulation factor

Answer 30

Platelet-derived growth factor

Question 31

"Tear drop" red cells are seen in which conditions?

Answer 31

Idiopathic myelofibrosis

Question 32

How does myelofibrosis present?

Answer 32

Marrow failure - anaemia, bleeding, infection Splenomegaly Extramedullary haemopoeisis

Question 33

Which mutations are seen in myelofibrosis?

Answer 33

JAK2 | CALR

Question 34

How is idiopathic myelofibrosis treated?

Answer 34

Transfusions Abx Allogenic stem cell transplant JAK2 inhibitors

Question 35

Give an example of a JAK2 inhibitor

Answer 35

Ruxolitinib

Question 36

What is the most common cause of raised cell counts?

Answer 36

Reactive

Question 37

What characterises CML?

Answer 37

Uncontrolled growth of myeloid cells

Question 38

Why is there less growth of non-myeloid cells in CML?

Answer 38

Overgrowth of myeloid cells push out the other cells and stop them growing

Question 39

Which gene is abnormal in CML?

Answer 39

BCR-ABL1

Question 40

Which chromosomal mutation is present in CML?

Answer 40

t(9;22) | Philadelphia chromosome

Question 41

Where is the abnormal ABL gene in CML?

Answer 41

Chromosome 9

Question 42

What is the effect of BCR-ABL mutations on DNA repair?

Answer 42

Inhibitory

Question 43

Why may upper abdo pain be present in CML?

Answer 43

Hepatosplenomegaly

Question 44

Why may CML cause poor appetite?

Answer 44

Spleen compresses stomach

Question 45

What does FBC show in CML?

Answer 45

Leucocytosis Increased white cells Normocytic/normochromic anaemia

Question 46

Why is gout more common in CML?

Answer 46

Increased cell turnover causes excess of purines

Question 47

Why does CML cause dyspnoea and fatigue?

Answer 47

Anaemia

Question 48

What causes the neurological defects in CML?

Answer 48

Hyperviscosity of the blood

Question 49

What are the three main stages of CML?

Answer 49

Chronic Accelerated Blast crisis

Question 50

Describe the chronic phase of CML

Answer 50

Asymptomatic | Mild fatigue or fullness

Question 51

Describe the accelerated phase of CML

Answer 51

Sign that disease is progressing and blast crisis is imminent

Question 52

What are the criteria for accelerated CML phase

Answer 52

Platelet counts <100,000 or >1,000,000 Increasing splenomegaly 10-19% myeloblasts >20% basophils

Question 53

Describe the blast crisis phase of CML

Answer 53

Final phase which behaves like an acute leukaemia

Question 54

What are the criteria for blast crisis CML?

Answer 54

>20% myeloblasts or lymphoblasts in blood or marrow Large clusters of blasts in bone marrow Chloroma

Question 55

What is a chloroma?

Answer 55

Extramedullary solid collection of leukaemia cells

Question 56

What does biochemistry show in CML?

Answer 56

Raised lactate dehydrogenase | Raised urate

Question 57

What does blood film show in CML?

Answer 57

Granulocytes at all stages of development

Question 58

How is CML managed?

Answer 58

Tyrosine kinase inhibitors | Bone marrow transplant

Question 59

Give an example of a tyrosine kinase inhibitor?

Answer 59

Imatinib

Question 60

How is response to imatinib treatment monitored?

Answer 60

PCR of BCAR-ABL

Question 61

When would a bone marrow transplant be offered in CML?

Answer 61

No response to medical treatment Young, healthy patient Offers cure