Myeloproliferative disorders Flashcards
What cell do myeloproliferative disorders arise from?
Common myeloid progenitor cell
How is haematopoesis controlled?
Through interaction between GF and GF receptors
This interaction activates TKs
Which kinases play an important role in Ph- MPD?
JANUS KINASES (JAK)
How do GF control haematopoesis?
GF binds to GF receptor
This activates JAK
JAK causes STAT pathway activation
This leads to cell growth and differentiation
What occurs in myeloproliferation in terms of differentiation and proliferation?
Differentiation and Proliferation occur
What occurs in leukaemia in terms of differentiation and proliferation?
Proliferation
Little/no differentiation
What occurs in myelodysplastic syndrome in terms of differentiation and proliferation?
INEFFECTIVE proliferation and differentiation
Which mutation triggers polycythaemia vera?
JAK2 V617F
What occurs in polycythaemia vera?
Increased production of RBC (high Hb, Htc)
Independent of mechanisms that regulate EPO
There is also a compensatory increase in plasma volume
What are symptoms of polycythaemia vera?
Hyperviscosity:
- headache, dizziness, stroke
- visual disturbance
- fatigue, dyspnoea
Increased histamine release
- aquagenic pruritus
- peptic ulceration
Splenomegaly Plethora Eruthromelalgia Thrombosis Retinal vein engorgement gout (due to increased RBC turnover, causing increased uric acid production)
How do you investigate polycythaemia vera?
FBC
Bone marrow biopsy(increased cellularity)
Low EPO (suppression via neg feedback loop)
JAK2 V617F mutation (DIAGNOSTIC)
Isotope dilution
What should you consider if a patient with polycythaemia clinical picture is JAK2 negative?
Consider pseudopolycythaemia
Consider secondary polycythaemia
What is treatment for polycythaemia vera?
Reduce viscosity (Hct <45%)
- Venesection
- Cytoreductive therapy
Reduce thrombotic risk
- Aspirin
- Platelets <400
What is idiopathic erythrocytosis?
Isolated erythrocytosis (with low EPO)
NO JAK2 V617F mutation
Occasionally JAK2 Exon 12 mutation
Whats the prognosis of idiopathic erythrocytosis?
Normal life
What are causes of death in PV?
Thrombosis
Leukaemia
Myelofibrosis
What is essential thrombocythaemia?
Sustained thrombocytosis >600
Involves PLATELETS ONLY
What is the clinical presentation of essential thrombocythaemia?
INCIDENTAL FINDING
Thrombosis (CVA, gangrene, TIA, DVT/PE)
Bleeding
Headache,dizziness, visual disturbance
What are diagnostic criteria for essential thrombocythaemia?
Platelet count above 600
Mekacaryocyte clustering
No evidence of reactive thrombocytopenia ptosis (infection)
JAK2 V617 mutation
In what ratio of essential thrombocythaemia is JAK2 V617F mutation present?
50% of patients
What is the treatment for ET?
Aspirin (prevents thrombosis)
Anagrelide
Hydroxycarbamide
Alpha-interferon
What is chronic myelofibrosis?
Chronic myeloproliferative disease with proliferation of megakaryocytic and granulocytic cells
Causes reactive bone marrow fibrosis and extramedullary haematopoesis
Clinical presentation of myelofibrosis
anaemia, thrombocytopenia
splenomeg/hepatomeg
Hypermetabolic state
Stages of myelofibrosis
Pre-fibrotic: hypercellular marrow, mild blood changes
Fibrotic: DRY TAP, splenomegaly, collagen fibrosis, osteosclerosis
What are blood film findings for myelofibrosis?
Leukoerythroblastic picture (nucleated red cells)
Tear drop poikilocytes
Giant platelets
Circulating megakaryocytic
How is the bone marrow investigated in myelofibrosis=
Dry tap
Trephine biopsy
How is myelofibrosis treated? Based on presentation
Anaemia > transfusion
Platelet transfusion
Splenecomy
Cryoreductive therapy: hydroxycarbamide, thalidomide
