Haematology - Myeloproliferative Disorders Flashcards
What are myeloproliferative disorders?
A group of conditions characterise by clonal proliferation of one or more haemopoeitic components
- e.g. increased production of mature cells
What myeloproliferative disorders are philadelphia chromosome positive?
Chronic myeloid leukaemia
What myeloproliferative disorders are philadelphia chromosome negative?
- Polycythaemia Vera
- Myelofibrosis
- Essential thrombocytosis
What mutation is associated with Ph -ve myeloproliferative disorders, and what is this associated with?
- JAK2 mutation
- Especially polycythaemia Vera (>95%)
A/w:
- Variable increases in reactive polyclonal BM fibrosis
- Terminal acute leukaemia transformation
What is polycythaemia?
A raised red cell mass, Hb, RCC + packed cell volume
What are some primary causes of polycythaemia?
- Polycythaemia vera
- Familial polycythaemia
What are some secondary causes of polycythaemia?
- Disease states (e.g. renal cancer)
- High altitudes
- Chronic hypoxia (e.g. COPD)
What is relative (pseudo) polycythaemia?
When the red cell mass is normal but the plasma volume is reduced
What are some causes of a relative (pseudo) polycythaemia?
- Dehydration
- Burns
- Vomiting
- Diarrhoea
- Cigarette smoking
What is polycythaemia rubra vera?
- A myeloproliferative disorder where erythroid precursors dominate the BM
- Incidence increases with age
What are the point mutations in polycythaemia rubra vera?
- JAK2 (V617F) - 95%
What are the clinical features of polycythaemia rubra vera?
- Hyperviscosity/hypervolaemia/hypermetabolism
- Blurred vision, headache
- Plethoric (red nose), gout, thrombosis + stroke, retinal vein engorgement, erythromelagia
- Splenomegaly
- Histamine release = aquagenic pruritis + peptic ulcers
What are some investigative findings for a patient with polycythaemia rubra vera?
- Raised Hb, Hct + ?Plts, WCC
- Low serum EPO
What is the treatment for polycythaemia rubra vera?
- Venesection
- Hydroxycarbamide (maintenance), aspirin
What complications is polycythaemia rubra vera at risk of?
Transformation into myelofibrosis/AML
What is myelofibrosis?
A myeloproliferative disorder where this is fibrosis of the BM or replacement with collagenous tissue
What is a primary cause of myelofibrosis?
Idiopathic
What are some secondary causes of myelofibrosis?
- polycythaemia rubra vera
- Essential thrombocytosis
- Leukaemia
What are some clinical features of myelofibrosis?
- Usually elderly
- Pancytopenia-related Sx
- Extramedullary haematopoeisis (hepatomegaly + MASSIVE SPLENOMEGALY)
- ?Present with Budd-Chiari Syndrome
What are some investigative findings of myelofibrosis?
Blood film:
- TEAR DROP POIKILOCYTE (Dacrocyte)
- Leukoerythroblasts (primitive cells)
Bone Marrow:
- Fibrosis
- DRY TAP
- Pancytopenia
Molecular Tests:
- JAK2 mutation (60%)
- MPL mutation
- CALR mutation
What is the treatment for myelofibrosis?
- Support with blood products
- ?splenectomy
- SCT = Only curative option
- JAK inhibitor = ruloxitinib, hydroxycarbamide, thalidomide, steroids
What is myelofibrosis at risk of transforming into?
AML
What is essential thrombocythaemia?
A myeloproliferative disorder where megakaryocytes dominate the BM
What mutations is essential thrombocythaemia associated with?
- JAK2 (50%)
- MPL mutation
- CALR
What are some clinical features of essential thrombocythaemia?
- Incidental finding in >50%
- Venous + arterial thrombosis (stroke + MI), gangrene, haemorrhage
- Erythromelalgia (burning + redness in hands + feet)
- Splenomegaly
- dizziness
- Headahce
- Visual disturbances
What investigative findings are seen in essential thrombocythaemia?
- Plt count >600 X 10^9 (consistent + no other cause)
Blood Film:
- Large plts
- Megakaryocyte fragments
Bone Marrow:
- Increased megakaryocytes (not reactive)
What is the treatment for essential thrombocythaemia?
- Aspirin (reduce stroke risk)
- ANAGRELIDE - reduce transformation of plts from megakaryocytes
- Hydroxycarbamide
