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Path- Haem Qs laz > Myeloproliferative Disorders > Flashcards

Myeloproliferative Disorders Flashcards

1
Q

What controls haemopoiesis?

A

Growth factors (e.g. EPO)

Receptors (mainly tyrosine kinases)

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2
Q
  1. What are Janus Kinases?
A

A family of four tyrosine kinase receptors associated with haemopoietic cell growth factor receptors

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3
Q
  1. Describe what happens when growth factors bind to Janus Kinase receptors.
A

Binding of the growth factors leads to activation of JAK, which activates the STAT pathway

STAT is a transcription factor that moves to the nucleus and promotes the transcription of genes associated with cell growth and proliferation

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4
Q
  1. What is a chronic myeloproliferative disorder?
A

A group of clonal disorders of haemopoietic stem cells characterised by the overproduction of one or more mature myeloid cellular elements in the blood

There is a trend towards increased fibrosis in the bone marrow

Some cases will develop into acute leukaemia

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5
Q
  1. Outline the usual presentation of myeloproliferative disorders.
A

Preponderance to thrombosis

Splenomegaly

Haemorrhage

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6
Q
  1. List some chronic myeloproliferative disorders.
A

Polycythaemia vera

Essential thrombocythaemia

Idiopathic myelofibrosis

Idiopathic erythrocytosis

Chronic granulocytic leukaemia

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7
Q
  1. What are the key differences between:
    a. Myeloproliferative disorder
    b. Leukaemia
    c. Myelodysplastic syndrome
A

a. Proliferation with full differentiation
b. Proliferation with little/no differentiation
c. Abnormal proliferation and abnormal differentiation

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8
Q
  1. What is polycythaemia vera?
A

A myeloproliferative disorder characterised by increased production of red cells (independent of normal control mechanisms) with a compensatory increase in plasma volume

Often accompanied by a degree of increased platelets and granulocytic cells

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9
Q
  1. Describe the clinical presentation of polycythaemia vera.
A

Incidental finding

Symptoms of hyperviscosity (headaches, visual disturbances, fatigue, dyspnoea)

Increased histamine release (Aquagenic pruritus, peptic ulceration)

Splenomegaly

Plethora

Erythromelalgia (red painful extremities)

Thrombosis

Retinal vein engorgement

Gout

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10
Q
  1. Outline the typical investigation findings in polycythaemia vera.
A

High haemoglobin, Hct, MCV, plasma volume and platelets

NO circulating immature cells

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11
Q
  1. Describe the appearance of a bone marrow biopsy in polycythaemia vera.
A

Increased cellularity (mainly erythroid cells)

Slight reticulin fibrosis and megakaryocyte abnormalities

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12
Q
  1. What investigation finding is considered diagnostic of polycythaemia vera?
A

Presence of JAK 2 V617F mutation

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13
Q
  1. How is red cell mass and plasma volume measured?
A

Isotope dilution

Red cells are incubated with radioactive chromium

Plasma is incubated with radioactive iodine

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14
Q
  1. What is pseudopolycythaemia?
A

Reduced plasma volume in the presence of a normal amount of haemoglobin results in an apparently raised Hb

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15
Q
  1. On which exon is the JAK2 V617F mutation found?
A

Exon 14

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16
Q
  1. Which other JAK mutation is a significant finding and which condition is it associated with?
A

Exon 12 mutation

It is associated with idiopathic erythrocytosis

17
Q
  1. What are some causes of JAK 2 V617F negative polycythaemia?
A

Pseudopolycythaemia

True polycythaemia that is secondary to increased EPO (e.g. hypoxia, renal disease, tumours)

18
Q
  1. Outline the principles of treatment of polycythaemia vera.
A

Reduce viscosity and keep Hct < 45%

· Venesection

· Cytoreductive therapy

Aim to reduce risk of thrombosis

· Aspirin

· Keep platelets < 400 x 109/L (same as ET treatment)

19
Q
  1. What is idiopathic erythrocytosis?
A

Isolated erythrocytosis with low EPO

Treated with venesection only

NO JAK 2 V617F mutation, but some cases will have an exon 12 mutation

20
Q
  1. Outline the prognosis of idiopathic erythrocytosis and polycythaemia vera.
A

Idiopathic erythrocytosis – no adverse prognosis if Hct is maintained

Polycythaemia vera – most survive 10 years, causes of death include thrombosis, leukaemia and myelofibrosis

21
Q
  1. What is essential thrombocythaemia?
A

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

22
Q
  1. Describe the typical clinical presentation of essential thrombocythaemia.
A

Incidental finding

Thrombosis (e.g. CVA, DVT, gangrene)

Bleeding

Headaches, dizziness and visual disturbances

23
Q
  1. What proportion of essential thrombocythaemia patients have JAK 2 mutations?
A

50%

24
Q
  1. Outline the treatment options for essential thrombocythaemia.
A

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)

25
Q
  1. What factor is important in determining risk level in patients with essential thrombocythaemia?
A

Age (old age = higher risk)

Also platelet count and whether symptomatic or not

26
Q
  1. Describe the prognosis of essential thrombocythaemia.
A

Normal life span

Leukaemic transformation in about 5% of patients after 10 years

Myelofibrosis is uncommon

27
Q
  1. Define chronic idiopathic myelofibrosis.
A

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

28
Q
  1. Describe the typical clinical presentation of myelofibrosis.
A

Incidental finding

Cytopaenias

Thrombocytosis

Splenomegaly (can be MASSIVE)

Hepatomegaly

FLAWS

Gout

29
Q
  1. Describe the two stages of myelofibrosis.
A

Pre-fibrotic = blood changes are mild with hypercellular marrow

Fibrotic = splenomegaly, blood changes, dry tap, prominent fibrosis and later osteosclerosis

30
Q
  1. Describe the appearance of myelofibrosis on a blood film.
A

Leukoerythroblastic picture

Tear drop poikilocytes

31
Q
  1. What are some features of the bone marrow in myelofibrosis?
A

Dry tap

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

32
Q
  1. Outline the treatment options for myelofibrosis.
A

Symptomatic treatment (e.g. transfusions for anaemia)

Splenectomy

Cytoreductive therapy (hydroxycarbamide and thalidomide)

Bone marrow transplant (in younger patients)

33
Q
  1. Describe the prognosis of myelofibrosis.
A

Median 3-5 year survival

34
Q
  1. Describe the structure of janus kinases.
A

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

35
Q
  1. What effect does the JAK 2 V617F mutation have on janus kinases?
A

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

36
Q
  1. Which other mutations of JAK have been associated with myeloproliferative diseases?
A

Exon 12 mutation of the JAK2 gene

Mutations in thrombopoietin receptors

NOTE: many patients have NO known mutations

37
Q
  1. Describe the use of bone marrow examination in:
    a. Polycythaemia vera
    b. Essential thrombocythaemia
    c. Myelofibrosis
A

a. Not needed in PV with JAK 2 mutations
b. May be helpful if JAK 2 negative
c. Always needed

Path- Haem Qs laz (4 decks)

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