Polycythaemia & Myelofibrosis

Question 1

What is polycythaemia?

Answer 1

Rise in RBCs

Question 2

What is a 1ary cause of polycythaemia?

Answer 2

Polycythaemia rubra vera

Question 3

What are some 2ary causes of polycythaemia? (4)

Answer 3

1) COPD

2) Altitude

3) Obstructive sleep apnoea

4) Excessive EPO:
- cerebellar haemangioma
- hypernephroma
- hepatoma
- uterine fibroids

Question 4

What are 2 causes of relative polycythaemia?

Answer 4

1) dehydration

2) stress: Gaisbock syndrome

Question 5

What is polycythaemia vera?

Answer 5

A myeloproliferative disorder caused by clonal proliferation of a marrow stem cell leading to an increase in red cell volume.

This is often accompanied by overproduction of neutrophils and platelets.

Question 6

What is a myeloproliferative disorder?

Answer 6

A group of rare disorders of the bone marrow that cause an increase in the number of blood cells

Question 7

What mutation is present in approx 95% of patients with polycythaemia vera?

Answer 7

JAK2 mutation

Question 8

Peak age of incidence of polycythaemia vera?

Answer 8

60-70 y/o

Question 9

What does the JAK2 gene encode for?

Answer 9

A non-receptor tyrosine kinase involved in EPO.

Mutation results in activation of this pathway –> increased proliferation and survival of hematopoietic progenitor cells, independent of EPO stimulation.

Question 10

What is the hallmark of polycythaemia vera?

Answer 10

Increased production of RBCs

Question 11

Why can patients with polycythaemia vera also present with raised WCC and raised platelets?

Answer 11

As the JAK2 mutation also influences the proliferation of other myeloid progenitor cells.

Question 12

How can PV affect viscosity of blood?

Answer 12

Overproduction of blood cells results in increased blood viscosity.

Question 13

Complications of hyperviscosity seen in PV?

Answer 13

Increased risk of thrombotic events:

1) DVT
2) PE
3) Arterial thrombosis e.g. stroke, MI

Question 14

Complications of the increased blood volume seen in PV?

Answer 14

Venous congestion and engorgement of organs:
- hepatomegaly
- splenomegaly

Question 15

Clinical features of PV?

Answer 15

1) Hyperviscosity

2) Pruritus, typically after a hot bath

3) Splenomegaly

4) Haemorrhage (secondary to abnormal platelet function)

5) Plethoric appearance

6) HTN in a third of patients

Question 16

What is the diagnostic criteria for PV? (2)

Answer 16

1) High haematocrit (>0.52 in men, >0.48 in women) OR raised red cell mass (>25% above predicted)

2) Mutation in JAK2

Diagnosis requires BOTH criteria to be present.

Question 17

Mx of PV?

Answer 17

1) Aspirin

2) Venesection –> 1st line

3) Hydroxyurea

4) Phosphorus-32 therapy

Question 18

Mx of PV with hydroxyurea carries a slightly increased risk of what?

Answer 18

2ary leukaemia

Question 19

3 key complications of PV?

Answer 19

1) Thrombotic events

2) Myelofibrosis (5-15% of patients progress)

3) Acute leukaemia (5-15% of patients progress & risk increased with chemotherapy treatment)

Question 20

What is myelofibrosis?

Answer 20

A rare haem disorder where bone marrow is replaced with collagen and becomes fibrosed.

This results in:
- haematological abnormalities
- profound fatigue
- massive splenomegaly
- extramedullary haematopoiesis

Question 21

Mean survival of myelofibrosis?

Answer 21

6 years

Question 22

Peak age of incidence of myelofibrosis?

Answer 22

60-70y

Question 23

Features of myelofibrosis?

Answer 23

1) Severe fatigue

2) Hepatosplenomegaly

3) B symptoms (20%

4) Signs of anaemia

5) Thromboembolic events (2ary to thrombocytosis)

6) Unexplained bleeding (2ary to thrombocytopenia)

Approx 20% patients may be asymptomatic.

Question 24

Where are the 2 most common sites of extramedullary haematopoiesis in myelofibrosis?

Answer 24

Liver & spleen

Question 25

What may a FBC show in myelofibrosis?

Answer 25

Pancytopenia

Question 26

What may a peripheral blood smear show in myelofibrosis?

Answer 26

Teardrop shaped red cells

Question 27

What will a bone marrow biopsy show in myelofibrosis?

Answer 27

fibrosis and abnormal megakaryocytes

Question 28

What is the most common mutation associated with myelofibrosis?

Answer 28

JAK2

Question 29

Give an example of a JAK2 inhibitor?

Answer 29

Ruxolitinib

Question 30

What is the most common cause of death in myelofibrosis?

Answer 30

Following a transformation to acute myeloid leukaemia.

Question 31

What leukaemia can myelofibrosis transform into?

Answer 31

AML