Haematology 4 - Chronic myeloproliferative neoplasms Flashcards
(30 cards)
What is the target of imatinib?
Mutated tyrosine kinase (by BCR-ABL gene)
What is the normal role of janus kinases?
They activate the STAT pathway, which promotes cell growth and replication (mainly myeloid)
How does JAK2 mutation cause uncontrollable replication?
No longer need growth factor to activate
In polycythaemia vera, what else will be abnormal on the FBC other than red cell count?
Pronounced thrombocytophilia and slight granulocytophilia
NO circulating immature cells
Recall some symptoms of polycythaemia vera
Due to hyperviscosity:
- Headaches
- visual disturbances
- dyspnoea
Due to increased histamine release:
- peptic ulcer (iron deficient polycythaemia = normal Hb but ↑ RBC and MCV)
- aquagenic pruritis
Recall four clinical findings in polycythaemia vera
Plethora
Erythromelalgia (red, painful extremities)
Gout
Retinal vein engorgement
What is the expected level of erythropoietin in polycythaemia vera?
low - suppression from feedback loop
What mutation is present in all patients with polycythaemia vera?
JAK2
What would bone marrow trephine biopsy show in polycythaemia vera ?
↑ cellularity (mainly affecting erythroid cells) – i.e. no fat spaces
Slight moderate reticulin fibrosis and megakaryocyte abnormalities
How should pseudopolychthaemia and polycythaemia vera be differentiated?
Isotype dilution method
↓ plasma volume, normal hb → apparent ↑ Hb
true → ↑ RBC mass with a roughly proportional increase in plasma volume
Recall 3 causes of increased EPO
Hypoxia
Uterine myoma
Renal cancer
Recall 3 causes of pseudopolycythaemia
Alcohol
Obesity
Diuretics
Recall 3 ways in which polycythaemia vera can be treated
- Venesection
- Cytoreductive therapy
- Aspirin to reduce thrombosis risk
What is idiopathic erythrocytosis?
An isolated erythrocytosis with low EPO, where JAK2 V617 mutation is absent (although JAK mutation in exon 12 may be present)
How should idiopathic erythrocytosis be treated?
Venesection only
What is the prognosis of idiopathic erythrocytosis and polycythaemia vera?
Idiopathic Erythrocytosis
NO adverse prognosis if Hct is maintained
Less likely → MF/AML
Polycythaemia Vera:
thrombosis, leukaemia (increased with hydroxyurea), myelofibrosis
How is essential thrombocytothaemia defined?
Chronic myeloproliferative neoplasm with a sustained thrombocytosis > 600 x 10^9/L
Which age group is most at risk of essential thrombocytothaemia?
Bimodal:
Small peak at 30y (M=F)
Larger peak at 55y (F>M)
What are the 2 most likely presentations for patients with essential thrombocytothaemia?
Thrombosis (arterial or venous)
CVA, gangrene, TIA
DVT, PE
Bleeding: mucous membrane and cutaneous
paradoxically
Minor: headaches, dizziness, visual disturbances
Splenomegaly is usually modest
Is there a JAK2 mutation in essential thrombocytothaemia?
Yes in 50%
What is the best treatment for essential thrombocytothaemia?
Hydroxycarbamide
antimetabolite - suppresses other cells as well
Possible mildly leukaemogenic
also aspirin, anagrelide (specific inhibition of Plt formation) and alpha-interferon
Which condition is “tear drop poikilocytosis” pathognemonic of?
Myelofibrosis
Which cells are hyperproliferating in myelofibrosis?
Mostly megakaryocytes and granulocytes
Define chronic idiopathic Myelofibrosis
clonal myeloproliferative disease - proliferation mainly of megakaryocytes and granulocytic cells
reactive BM fibrosis and extramedullary haemopoiesis
Age: > 60 years; May occur secondary to other haematological disease (e.g. PV or ET)
