Myeloproliferative Disease

Question 1

What is meant by a myeloproliferative disease?

Answer 1

• “myelo” = type of cell lineage

- “proliferative” = grow/multiply rapidly

Question 2

How are myeloproliferative diseases different from acute leukaemias which also have a proliferation of blast cells?

Answer 2

Acute leukaemia = blast cells can’t mature

MPD = increased no. of blasts which can mature

Question 3

How are myeloproliferative diseases classified?

Answer 3

• Either BCR-ABL1 negative or positive

Negative:

• Myelofibrosis
• Polycythaemia Vera (PV) (increased RBCs)
• Essential Thrombocythaemia (increased platelets)

Positive:
- Chronic Myeloid Leukaemia (increased granulocytes)

Question 4

What blood count results would make you consider a myeloproliferative disorder?

Answer 4

increased granulocyte count
increased RBCs/Hb
increased platelets
Eosinophilia/Basophilia
Splenomegaly
Thrombosis in unusual place

Question 5

Chronic Myeloid Leukaemia can cause an increase in platelets and RBCs as well as granulocytes. TRUE/FALSE?

Answer 5

TRUE

Question 6

What are the clinical features of CML?

Answer 6

• can be asymptomatic
• splenomegaly
• hypermetabolic syndrome (early satiety and weight loss)
• Gout (due to increased DNA breakdown)

Question 7

What lab findings are common in CML?

Answer 7

• Normal or low Hb
• neutrophilia
• Increased myeloid precursors
• eosinophilia/basophilia
• increased platelets

Question 8

How can you differentiate chronic myeloid leukaemia from reactive change?

Answer 8

• reactive changes e.g. infection

- causes all WBCs to increase not just granulocytes

Question 9

What genetic abnormality is present in Chronic Myeloid Leukaemia?

Answer 9

Translocation between chromosome 9:22

“Philadelphia Chromosome”

Question 10

What does Polycythaemia Vera cause?

Answer 10

• increase in RBC production

=> increase in Hb, Hct and red cell mass

Question 11

What can cause SECONDARY polycythaemia?

Answer 11

• chronic hypoxia
• smoking
• erythropoietin secreting tumour (or EPO doping)

Question 12

What can cause PSEUDO polycythaemia?

Answer 12

plasma volume diminished so Hb and red cells look higher than they are

• dehydration
• diuretics
• obesity

Question 13

What symptoms other than those common to Myeloproliferative disorders are present in PV?

Answer 13

• headache
• fatigue
• increased blood viscosity
• itch

Question 14

What is usually identified on abdominal examination in patients with PV?

Answer 14

Splenomegaly

Question 15

What mutation is present in 90% of patients with PV?

Answer 15

JAK2 mutation

Question 16

What investigations are used to look for causes of SECONDARY and PSEUDO polycythaemia?

Answer 16

• CXR
• O2 sats
• arterial blood gas
• Drug Hx (check for diuretics/dehydration)

Question 17

How is PV treated?

Answer 17

• venesection to correct haematocrit <0.45
• aspirin (to lower platelets)
• cytotoxic oral chemo (e.g. hydroxycarbamide)

Question 18

What is essential thrombocythaemia?

Answer 18

• uncontrolled proliferation of platelets
• abnormal platelet function
• risk of thrombosis
• acquired von willebrands disease can occur and cause bleeding in late stage

Question 19

What are the main clinical features of Essential Thrombocythaemia?

Answer 19

• vasoocclusive

- bleeding if patient acquires von willebrand disease

Question 20

How can essential thrombocythaemia be diagnosed on blood film?

Answer 20

Isolated rise in platelets

Question 21

What reactive causes may cause a rise in platelets similar to essential thombocythaemia?

Answer 21

blood loss (e.g. due to surgery)
inflammation
malignancy
iron deficiency

other blood results would be abnormal in these cases though

Question 22

What genetic mutations are often present in essential thrombocythaemia?

Answer 22

JAK2
CALR
MPL
(but some patient’s will be triple negative)

Question 23

HOw is essential thrombocythaemia treated?

Answer 23

• antiplatelets => aspirin
• cytoreductive therapy (controls proliferation)
• e.g. hydroxycarbamide, interferon alpha

Question 24

When can myelofibrosis occur?

Answer 24

• idiopathic

- post-polycythaemia

Question 25

What features occur in idiopathic myelofibrosis?

Answer 25

marrow fails and becomes dry/ fibrosed

=> extramedullary haematopoiesis takes over

Question 26

What symptoms do patients with myelofibrosis experience?

Answer 26

• anaemia
• bleeding
• infection (as cant make granulocytes to fight it)
• splenomegaly (due to extramedullary haematopoiesis)

Question 27

What can be seen on a blood film in Myelofibrosis?

Answer 27

• tear drop shaped RBCs (Poikilocytes)

- leucoerythroblastic change (nucleated red cells and other early myeloid cells in film)

Question 28

Why is a trephine biopsy required in myelofibrosis?

Answer 28

• bone marrow aspiration will be dry due to fibrosis

Question 29

What cells are not found on a bone marrow biopsy if a patient has myelofibrosis?

Answer 29

• fat cells

- these are usually common in marrow biopsy

Question 30

How is myelofibrosis treated?

Answer 30

supportive treatments - transfusion, platelets, antibiotics

allogenic stem cell transplant

splenectomy

JAK2 inhibitors

Question 31

What reactive causes can increase granulocyte count?

Answer 31

Infection

physiological (i.e. post surgery/steroids)

Question 32

What reactive causes can increase the platelet count?

Answer 32

• infection
• iron deficiency
• malignancy
• blood loss

Question 33

What reactive causes can increase the RBC count?

Answer 33

• dehydration (pseudo due to low plasma)

- hypoxia (secondary)