Haematology 3s - myeloproliferative diseases Flashcards
Normal haumatopoeisis is regulated by…?What do they interact with?
Growth factors e.g. EPO
These interact with receptors –> tyrosine kinase activation
An important enzyme in haemopoiesis
JAK
Which cells is JAK2 mainly implicated in?
Myeloid cells
Mutation in JAK…
Constitutive activation of the STAT pathway independent of cytokines binding to the receptor
Which mutation is diagnostic of PRV?
JAK2 V617F
What will some MPDs progress to?
Acute leukaemia
Name 3 myeloproliferative neoplasia which are BCR-ABL negative?
Polycythaemia rubra vera
Essential thrombocytosis
Myelofibrosis
How does blood from MPN patients behave on agar culture?
Cells will grow in absence of EPO or TPO
2 main features of MPNs?
Common presentations?
BM fibrosis
Increased proliferation of MATURE cells
2 mutations seen in MPNs?
JAK2 and Exon 12
Clinical features of PRV
Sx of hyperviscocity Increased histamine release --> aquagenic pruritis and peptic ulceration Variable splenomegaly Erythromelalgia Thrombosis (Arterial) Retinal vein engorgement Gout
Epidemiology for PRV - age? sex?
M>F
>60
Haem Ix in PRV?
High Hb High HCT High MCV High plts NO circulating immature cells High plasma volume Low EPO
Specific investigations for PRV
BM trephine biopsy (increased cellularity, no fat spaces, reticulin fibrosis and megakaryocyte abnormality)
JAK2 V617F MUTATION = DIAGNOSTIC
Blood volume: measured by isotope dilution
Dx if pt has raised HCt with an JAK2 Exon 12 mutation?
Idiopathic erythrocytosis
If negative for JAK2 muataion and have polycythaemia
Could be pseudopolycythaemia, true polycythaemia i.e. secondary to EPO secretion
Current diagnostic criteria for PRV
Raised red cell production and increased platelets
JAK2 V617F mutation
Treatment of PRV
hCT <45% and plt <400x10^9
Venesection
hydroxycarbamide + aspirin
Features of idiopathic erythrocytosis
isolated erythrocytosis Less likely to transform in to MF or AML ABSENCE OF JAK2 V617F MUTATION Exon 12 mutation OF JAK2 Low EPO Treated with venesection only
Prognosis of PRV vs idiopathic erythrocytosis
PRV most survive 10 years (death by thrombosis, leukaemia, myelofibrosis)
Erythrocytosis: no adverse prognosis if Hct is maintained
What is the disorder?
- 2 age peaks at 30 and 55 yo
- BM dominated by megakaryocytes
- Blood film = large platelets
- Plt count >600*10^9
Essential thrombocythaemia
What % of pts with ET have JAK2 mutation
50% (some also have TPO mutation)
Treatment of ET
- Aspirin (prevent thrombosis)
- Hydroxycarbamide (can worsen anaemia)
- Anagrelide, reduces platelet formation (can transform to MF)
- alpha-IFN useful in <40yos.
Investigation results in ET
Platelets >600*10^9
Blood film: large platelets, megakaryocyte fragments
BM: megakaryocytes + clustering
V617F mutation in 50%
