Haem: Myeloproliferative Disorders Pt.1 Flashcards
What controls haemopoisesis?
Growth factors (e.g. EPO)
Receptors (mainly tyrosine kinases)
What are Janus Kinases?
A family of four tyrosine kinase receptors assocaited with haemopoietic cell growth factor receptos
Describe what happens when growth factors bind to Janus Kinase receptors.
- 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
What is a chronic myeloproliferative disorder?
- 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
Outline the usual presentation of myeloproliferative disorders.
- Predisposed to thrombosis
- Splenomegaly
- Haemorrhage
List some chronic myeloproliferative disorders.
- Polycythaemia vera
- Essential thrombocythaemia
- Idiopathic myelofibrosis
- Idiopathic erythrocytosis
- Chronic granulocytic leukaemia
What are the key differences between:
- Myeloproliferative disorder
- Leukaemia
- Myelodysplastic syndrome
- Myeloproliferative disorder = proliferation with full differentiation
- Leukaemia = proliferation with little/no differentiation
- Myelodysplastic syndrome = abnormal proliferation and abnormal differentiation
What is polycythaemia vera?
- 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
Describe the clinical presentation of polycythaemia vera.
- 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
Outline the typical investigation findings in polycythaemia vera.
- High haemoglobin, Hct, MCV, plasma volume and platelets
- NO circulating immature cells
Describe the appearance of a bone marrow biopsy in polycythaemia vera.
- Increased cellularity (mainly erythroid cells)
- Slight reticulin fibrosis and megakaryocyte abnormalities
What investigation finding is considered diagnostic of polycythaemia vera?
Presence of JAK 2 V617F mutation
How is red cell mass and plasma volume measured?
- Isotope dilution
- Red cells are incubated with radioactive chromium
- Plasma is incubated with radioactive iodine
What is pseudopolycythaemia?
Reduced plasma volume in the present of a normal amount of haemoglobin results in an apparently raised Hb
On which exon is the JAK2 V617F mutation found?
Exon 14
Which other JAK mutation is a significant finding and which condition is it associated with?
Exon 12 mutation
It is associated with idiopathic erythrocytosis
What are some causes of JAk 2 V617F negative polycythaemia?
- Pseudopolycythaemia
- True polycythaemia that is secondary to increased EPO (e.g. hypoxia, renal disease, tumours)
