Haem: Myeloproliferative Disorders Pt.1 Flashcards

1
Q

What controls haemopoisesis?

A

Growth factors (e.g. EPO)

Receptors (mainly tyrosine kinases)

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2
Q

What are Janus Kinases?

A

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

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3
Q

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

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

Outline the usual presentation of myeloproliferative disorders.

A
  • Predisposed to thrombosis
  • Splenomegaly
  • Haemorrhage
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6
Q

List some chronic myeloproliferative disorders.

A
  • Polycythaemia vera
  • Essential thrombocythaemia
  • Idiopathic myelofibrosis
  • Idiopathic erythrocytosis
  • Chronic granulocytic leukaemia
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7
Q

What are the key differences between:

  1. Myeloproliferative disorder
  2. Leukaemia
  3. Myelodysplastic syndrome
A
  1. Myeloproliferative disorder = proliferation with full differentiation
  2. Leukaemia = proliferation with little/no differentiation
  3. Myelodysplastic syndrome = abnormal proliferation and abnormal differentiation
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8
Q

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

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

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

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

What investigation finding is considered diagnostic of polycythaemia vera?

A

Presence of JAK 2 V617F mutation

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13
Q

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

What is pseudopolycythaemia?

A

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

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15
Q

On which exon is the JAK2 V617F mutation found?

A

Exon 14

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16
Q

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

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

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 <400x109/L (same as ET treatment)
19
Q

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

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