Haematology - Myeloproliferative Disorders

Question 1

What are myeloproliferative disorders?

Answer 1

A group of conditions characterise by clonal proliferation of one or more haemopoeitic components
- e.g. increased production of mature cells

Question 2

What myeloproliferative disorders are philadelphia chromosome positive?

Answer 2

Chronic myeloid leukaemia

Question 3

What myeloproliferative disorders are philadelphia chromosome negative?

Answer 3

• Polycythaemia Vera
• Myelofibrosis
• Essential thrombocytosis

Question 4

What mutation is associated with Ph -ve myeloproliferative disorders, and what is this associated with?

Answer 4

• JAK2 mutation
• Especially polycythaemia Vera (>95%)

A/w:
- Variable increases in reactive polyclonal BM fibrosis
- Terminal acute leukaemia transformation

Question 5

What is polycythaemia?

Answer 5

A raised red cell mass, Hb, RCC + packed cell volume

Question 6

What are some primary causes of polycythaemia?

Answer 6

• Polycythaemia vera
• Familial polycythaemia

Question 7

What are some secondary causes of polycythaemia?

Answer 7

• Disease states (e.g. renal cancer)
• High altitudes
• Chronic hypoxia (e.g. COPD)

Question 8

What is relative (pseudo) polycythaemia?

Answer 8

When the red cell mass is normal but the plasma volume is reduced

Question 9

What are some causes of a relative (pseudo) polycythaemia?

Answer 9

• Dehydration
• Burns
• Vomiting
• Diarrhoea
• Cigarette smoking

Question 10

What is polycythaemia rubra vera?

Answer 10

• A myeloproliferative disorder where erythroid precursors dominate the BM
• Incidence increases with age

Question 11

What are the point mutations in polycythaemia rubra vera?

Answer 11

• JAK2 (V617F) - 95%

Question 12

What are the clinical features of polycythaemia rubra vera?

Answer 12

• Hyperviscosity/hypervolaemia/hypermetabolism
• Blurred vision, headache
• Plethoric (red nose), gout, thrombosis + stroke, retinal vein engorgement, erythromelagia
• Splenomegaly
• Histamine release = aquagenic pruritis + peptic ulcers

Question 13

What are some investigative findings for a patient with polycythaemia rubra vera?

Answer 13

• Raised Hb, Hct + ?Plts, WCC
• Low serum EPO

Question 14

What is the treatment for polycythaemia rubra vera?

Answer 14

• Venesection
• Hydroxycarbamide (maintenance), aspirin

Question 15

What complications is polycythaemia rubra vera at risk of?

Answer 15

Transformation into myelofibrosis/AML

Question 16

What is myelofibrosis?

Answer 16

A myeloproliferative disorder where this is fibrosis of the BM or replacement with collagenous tissue

Question 17

What is a primary cause of myelofibrosis?

Answer 17

Idiopathic

Question 18

What are some secondary causes of myelofibrosis?

Answer 18

• polycythaemia rubra vera
• Essential thrombocytosis
• Leukaemia

Question 19

What are some clinical features of myelofibrosis?

Answer 19

• Usually elderly
• Pancytopenia-related Sx
• Extramedullary haematopoeisis (hepatomegaly + MASSIVE SPLENOMEGALY)
• ?Present with Budd-Chiari Syndrome

Question 20

What are some investigative findings of myelofibrosis?

Answer 20

Blood film:
- TEAR DROP POIKILOCYTE (Dacrocyte)
- Leukoerythroblasts (primitive cells)

Bone Marrow:
- Fibrosis
- DRY TAP
- Pancytopenia

Molecular Tests:
- JAK2 mutation (60%)
- MPL mutation
- CALR mutation

Question 21

What is the treatment for myelofibrosis?

Answer 21

• Support with blood products
• ?splenectomy
• SCT = Only curative option
• JAK inhibitor = ruloxitinib, hydroxycarbamide, thalidomide, steroids

Question 22

What is myelofibrosis at risk of transforming into?

Answer 22

AML

Question 23

What is essential thrombocythaemia?

Answer 23

A myeloproliferative disorder where megakaryocytes dominate the BM

Question 24

What mutations is essential thrombocythaemia associated with?

Answer 24

• JAK2 (50%)
• MPL mutation
• CALR

Question 25

What are some clinical features of essential thrombocythaemia?

Answer 25

• Incidental finding in >50%
• Venous + arterial thrombosis (stroke + MI), gangrene, haemorrhage
• Erythromelalgia (burning + redness in hands + feet)
• Splenomegaly
• dizziness
• Headahce
• Visual disturbances

Question 26

What investigative findings are seen in essential thrombocythaemia?

Answer 26

• Plt count >600 X 10^9 (consistent + no other cause)

Blood Film:
- Large plts
- Megakaryocyte fragments

Bone Marrow:
- Increased megakaryocytes (not reactive)

Question 27

What is the treatment for essential thrombocythaemia?

Answer 27

• Aspirin (reduce stroke risk)
• ANAGRELIDE - reduce transformation of plts from megakaryocytes
• Hydroxycarbamide