Haem: Myeloproliferative Disorders Pt.2

Question 1

What is essential thrombocythaemia?

Answer 1

Myeloproliferative disorder mainly involving the megakaryocyte lineage (platelet count > 600 x 10⁹/L)

Question 2

Describe the typical clinical presentation of essential thrombocythaemia.

Answer 2

• Incidental finding
• Thrombosis (e.g. CVA, DVT, gangrene)
• Bleeding
• Headaches, dizziness and visual disturbances

Question 3

What proportion of essential thrombocythaemia patients have JAK 2 mutations?

Answer 3

50%

Question 4

Outline the treatment options for essential thrombocythaemia.

Answer 4

• Aspirin
• Anagrelide (specific inhibitor of platelet formation - may accelerate myelofibrosis)
• Hydroxycarbamide (MAIN TREATMENT - may be leukaemogenic)
• Alpha-interferon (may be used in patients < 40 years)

Question 5

What factor is important in determining risk level in patients with essential thrombocythaemia?

Answer 5

Age (old age = higher risk)

Also platelet count and whether symptomatic or not

Question 6

Describe the prognosis of essential thrombocythaemia.

Answer 6

• Normal life span
• Leukaemic transformation in about 5% of patients after 10 years
• Myelofibrosis is uncommon

Question 7

Define chronic idiopathic myelofibrosis.

Answer 7

A clonal myeloproliferative disease with proliferation mainly of megakaryocytes and granulocytic cells, associated with reactive bone marrow fibrosis and extramedullary haemopoesis

Question 8

Describe the typical clinical presentation of myelofibrosis.

Answer 8

• Incidental finding
• Cytopaenias
• Thrombocytosis
• Splenomegaly (can be MASSIVE)
• Hepatomegaly
• FLAWS
• Gout

Question 9

Describe the two stages of myelofibrosis.

Answer 9

• Pre-fibrotic = blood changes are mild with hypercellular marrow
• Fibrotic = splenomegaly, blood changes, dry tap, prominent fibrosis and later osteosclerosis

Question 10

Describe the appearance of myelofibrosis on a blood film.

Answer 10

• Leukoerythroblastic picture
• Tear drop poikilocytes

Question 11

What are some features of the bone marrow in myelofibrosis?

Answer 11

• Dry tap
• Trephine biopsy will show increased reticulin or collagen fibrosis, prominent megakaryocyte hyperplasia and new bone formation

Question 12

Outline the treamtent options for myelofibrosis.

Answer 12

• Symptomatic treatment (e.g. transfusions for anaemia)
• Splenectomy
• Cytoreductive therapy (hydroxycarbamide and thalidomide)
• Bone marrow transplant (in younger patients)

Question 13

Describe the prognosis of myelofibrosis.

Answer 13

Median 3-5 year survival

Question 14

Describe the structure of janus kinases.

Answer 14

They have a kinase domain and a catalytically inactive pseudokinase domain with regulatory function

Question 15

What effect does the JAK 2 V617F mutation have on janus kinases?

Answer 15

It inactivates the pseudokinase domain thereby removing inhibition of activation so it becomes constitutively activated.

Question 16

Which mutations, other than JAK 2 V617F, have been associated with myeloproliferative diseases?

Answer 16

• Exon 12 mutation of the JAK2 gene
• Mutations in thrombopoietin receptors

NOTE: many patients have NO known mutations

Question 17

Describe the use of bone marrow examination in:

1. Polycythaemia vera
2. Essential thrombocythaemia
3. Myelofibrosis

Answer 17

1. Polycythaemia vera - not needed in PV with JAK 2 mutations
2. Essential thrombocythaemia - may be helpful if JAK 2 negative
3. Myelofibrosis - always needed