Myeloproliferative disorders

Question 1

What are the types of myeloproliferative disorders

Answer 1

Primary myelofibrosis
Polycythaemia vera
Essential thrombocythaemia

Question 2

What is the proliferating cell line in primary myelofibrosis?

Answer 2

Haematopoietic stem cells

Question 3

What is the proliferating cell line in polycythaemia vera?

Answer 3

Erythroid cells

Question 4

What is the proliferative cell line in essential thrombocythaemia?

Answer 4

Megakaryote cells

Question 5

These conditions are associated with mutations in which genes?

Answer 5

JAK
MPL
CALR

Question 6

What can patients with myeloproliferative disorders present with?

Answer 6

Can be asymptomatic or systemic symptoms:
Fatigue
Weight loss
Night sweats 
Fever

Question 7

Why do myeloproliferative disorders occur?

Answer 7

Due to uncontrolled proliferation of a single type of stem cell - they are considered a type of bone cancer

Question 8

What is a type of treatment for myeloproliferative disorders?

Answer 8

JAK2 inhibitors e.g. ruxolitinib

Question 9

What is myelofibrosis?

Answer 9

Where proliferation of the cell line leads to bone marrow fibrosis
Can happen in primary myelofibrosis, polycythaemia vera or essential thrombocythaemia

Question 10

What happens in myelofibrosis (pathophysiology)?

Answer 10

The bone marrow is replaced scar tissue in response to cytokines released from proliferating cells e.g. of a cytokine = fibroblast growth factor

Question 11

What is extramedullary haematopoiesis?

Answer 11

Bone marrow is replaced with scar tissue so the haematopoiesis happens outside of the bone marrow e.g. in the liver or the spleen leading to hepatomegaly and splenomegaly

Question 12

What can the hepatomegaly and splenomegaly lead to?

Answer 12

Portal hypertension

Question 13

If the haematopoiesis happens around the spine, what could this lead to?

Answer 13

Spinal cord compression

Question 14

What are the signs and symptoms of underlying complications?

Answer 14

Anaemia - except in PV
Splenomegaly - causing abdominal pain
Portal hypertension - ascites, varices, abdo distension
Thrombocytopenia - bleeding and petechiae
Thrombosis is common in polycythaemia and thrombocythaemia
Raised RBCs - red face and thrombosis
Low white cells - infections

Question 15

What are the full blood count findings

Answer 15

Polycythaemia vera: raised Hb >185g/l in men and >165g/l in women
Essential thrombocythaemia - raised platelet count >600x10^9/L
Myelofibrosis - due to primary MF or secondary to PV or ET
- Anaemia
- Leucocytosis or leucopenia
- Thrombocytosis or thrombocythaemia

Question 16

What does a blood film in myelofibrosis show?

Answer 16

Teardrop RBCs
Varying size of RBCs - anisocytosis
Immature red and white cells - blasts

Question 17

What is involved in diagnosis?

Answer 17

Bone marrow biopsy - bone marrow aspiration would be “dry” due to the fibrosis
Gene testing for JAK, MPL and CALR

Question 18

Management of primary myelofibrosis?

Answer 18

Mild disease: monitored and not actively treated
Allogeneic stem cell transplantation - usually curative but carries risk
Chemotherapy - can help to control disease & improve symptoms but isnt curative
Supportive management of the anaemia, splenomegaly and portal hypertension

Question 19

Management of polycythaemia vera

Answer 19

1st line = Venesection - used to keep Hb in normal range
Aspirin - reduces risk of clots
Chemotherapy to control disease

Question 20

Management of essential thrombocythaemia

Answer 20

Aspirin - reduce risk of thrombus formation

Chemotherapy to control the disease