Myeloproliferative Disorders

Question 1

What are myeloproliferative disorders?

Answer 1

A group of disorders characterised by proliferation of one or more haematopoietic components.

Question 2

How can you classify myeloproliferative disorders?

Answer 2

Philadelphia chromosome +ve
- Chronic myeloid leukaemia

Philadelphia chromosome -ve

• Polycythaemia vera
• Myelofibrosis
• Essential thrombocytosis

Question 3

What gene mutations are associated with myeloproliferative disorders?

Answer 3

JAK2 mutations

Question 4

Why is polycythaemia? Describe the causes

Answer 4

It is a raised red cell mass, haemoglobin, red cell count and packed cell volume

Causes are either primary or secondary to a raised EPO

Primary:

• Familial polycythaemia (JAK2 negative)
• Polycythaemia vera (JAK2 positive)

Secondary to high EPO:

• Renal cancer
• High altitude
• Hypoxia

Question 5

What is relative polycythaemia?

Answer 5

Also called pseudo polycythaemia, where there is no increase in the red cell mass, but a decrease in the plasma volume.

This can be caused by dehydration, burns, vomiting, diarrhoea or cigarette smoking

Question 6

What is polycythaemia vera? What is the associated epidemiology? Describe the clinical features and investigations involved. How is it treated?

Answer 6

Also called polycythaemia rubra vera.

A myeloproliferative disorder where erythroid precursors predominate the BM. It is associated with a specific JAK2 mutation, V617F.

It occurs at 203:100,00 with M>F and the mean age at 60 years.

Clinically, it causes Hyperviscosity, blurred vision, plethora, thrombosis, erythromelalgia, splenomegaly, aquagenic pruritus.

Investigations involve Hb (raised), HCT (raised), platelets, WCC and EPO (low)

It is treated acutely with venesection, and more long-term with hydroxycarbamide.

Question 7

What is myelofibrosis? Describe the clinical features and investigations involved. How is it treated?

Answer 7

A myeloproliferative disorder where chronic myeloproliferation causes fibrosis of the BM and replacement with collagenous tissue. It can be primary or secondary.

Clinically, it is usually in elderly patients, with pancytopaenic symptoms and a raised metabolic state.

Investigations include a blood film (tear drop poikilocytes and leukoerythroblasts) and BM tap (dry tap, fibrosis)

It is treated with blood product support, hydroxycarbamide and thalidomide (limited use)

Question 8

What is essential thrombocytosis? What is the associated epidemiology? Describe the clinical features and investigations involved. How is it treated?

Answer 8

A myeloproliferative disorder where megakaryocytes predominate the BM. Up to a half of cases are associated with a JAK2 mutation.

It has a bimodal peak at 55 and 30, with male and female incidence being equal except in younger populations where females are more at risk.

The clinical features include venous and arterial thrombosis, erythromelalgia, splenomegaly and dizziness. It is an incidental finding in 50% of the cases.

Investigations involve a platelet count (>600), a blood film (large platelets, megakaryocyte fragments) and increased BM megakaryocytes.

It is treated on the basis of risk, with higher risk patients being treated only. Higher risk patients are those above 60, symptomatic, with a platelet count of >1000, or with other thrombotic risk factors. It is treated with aspirin, hydroxycarbamide and anagrelide (reduced platelet formation).