Haematology 4: Myeloproliferative Disorders Flashcards
What are the main differences between myeloproliferative and myelodysplastic disorders ?
Myelodysplastic syndromes have ineffective differentiation whereas in myeloproliferative disorders the cells are normal and fully differentiated.
Give 4 examples of chronic myeloproliferative disorders ?
Polycythaemia rubra Vera Essential thropmbocythaemia Idiopathic myelofibrosis Idiopathic erythrocytosis chronic granulocytic leukaemia
List 4 signs/symptoms of Polycythaemia rubra Vera ?
Aquagenic pruritus- itch after having a warm bath
Gout
Engorged retinal veins
Erythromelalgia- Red painful extremities
What levels would you expect in someone with Polycythaemia rubra Vera ?:
Hb :Low/High
Hct :Low/High
MCV: Low/High
EPO: Low/High
Hb: High
Hct: High
MCV: High
EPO: low (suppressed because of negative feedback)
How is Polycythaemia rubra Vera diagnosed ?
Bone marrow biopsy- Increased cellularity, low EPO, Reticulin fibrosis
JAK2 V617F mutation is diagnostic
What is pseudo polycythaemia ?
Reduced plasma volume in presence of a normal Hb conc.
What causes Polycythaemia where EPO is raised ?
Hypoxia- High altitude
Renal disease
tumours
What are the signs of Essential Thrombocythaemia ?
High platelet count
CVA
DVT/PE
Splenomegaly
What are the signs of Chronic idiopathic myelofibrosis ?
FLAWS
anaemia
Thrombocytosis
Hepatosplenomegaly (massive, sites for extra medullary haematopoeisis)
What is the characteristic finding of bone marrow aspiration in Chronic idiopathic myelofibrosis
Dry tap
Because of the fibrosis nothing comes out
what two things are important in the control of haemopoiesis
growth factors (EPO) receptors eg tyrosine kinase
which kinases are important in myeloproliferative neoplasms
BCR-ABL kinases (feature of CML) Janus KInases (JAK2)
describe the JAK signalling pathway
growth factors binding to receptors leads to activation of JAK
leads to activation of STAT pathway
JAK2 implicated in myeloid cells
STAT TF moves to the nucleus and causes transcription of genes associated with cell g+p
mutation that activates JAK constitutively means that activation of this pw not dependent on growth factor cytokines
describe BCR-ABL negative myeloproliferative disorders
overproduction of one or more mature myeloid cellular elements of the blood
increased fibrosis in the BM
some cases progress to acute leukaemia
spontaneous colonies with or without EPT/TPO
clinical presentations of myeloproliferative disorders
thrombosis (arterial)
splenomegaly
haemorrhage
difference between myeloproliferation, myelodysplasia and leukaemia
myeloproliferation = proliferation + full differentiation myelodysplasia = ineffective proliferation and differentiation leukaemia = proloferation and no/little differentiation
what is polycythaemia vera
increased production of RBC (high Hb and HCT)
independent of mechanisms that regulate haemopoiesis (EPO)
compensatory increase in plasma volume
accompanied by increase in platelets or granulocytic cells or both
mean age 60
clinical presentation of polycythaemia vera
incidental on blood screen hyperviscocity symptoms - headaches, visual dist, fatigue, dyspnoea increased histamine release - aquagenic pruritus, peptic ulceration (can cause iron def) variable splenomegaly plethora erythromelalgia thrombosis retinal vein encorgement gout
investigations for polythemia vera
high Hb high HCT high MCV high plasma volume high platelets no circulating immature cells low EPO JAK 2V16F mutation BM biopsy - increased cellularity, reticulin fibrosis and megakaryocyte abnormalities
diagnostic test for PV
JAK2 V617F mutation
positive = PV (exon 14) or eryhtrocytosis (exon 12)
negaive = pseudopolycthaemia or true polycythaemia secondary to EPO/familial
how is polycythaemia vera treated
reduce viscosity and keep HCT<45%
venesection
cytoreductive therapy
aspirin
features of idiopathic erythrocytosis
isolated erythrocytosis low EPO treated with venesection only absence of JAK2 V617F mutation some cases have a mutation in exon 12 of JAK2 no adverse prognosis if Hct maintained
what is essential thrombocythaemia
involves megakaryocyte lineage
incidental finding in 50%
thrombosis - CVA, gangrene, TIA, DVT, OE
bleeding - mucous membranes and cutaneous
minor - headaches, dizziness, visual dist
splenomagely is modest
diagnosis of essential thrombocythaemia
platelets consistently > 600x10 9 megakaryocyte abnormalities JAK 2 V617F mutation (in 50%) splenomegaly mild normal/slightly increased BM cellularity
treatment for essential thrombocytaemia
aspirin
anagrelide
HYDROXYCARBAMIDE (main tx) - antimetabolite
alpha interferon
what is chronic idiopathic myelofibrosis
clonal myeloproliferative disease with proliferation of megakaryocytes and granulocytes, associated with reactive BM fibrosis and extramedullary haemopoiesis
age >60
presentation of chronic idiopathic myelofibrosis
incidental cytopaenias thrombocytosis splenomegaly (may be massive) hepatomegaly hypermetabolic state - wt loss, fatigue, night sweats, hyperuricemia
what are the stages of myelofibrosis
pre-fibrotic - mild blood changes, hypercellular marrrow
fibrotic - splenomegaly, blood changes, dry tap
haematological findings of CIM
leucoerythroblastic picture
tear drop poikilocytes
giant platelets
circulating megakaryocytes
liver + spleen - extramedullary haemopoiesis
BM - dry tap, trephine biopsy (increased reticulin or collagen fibrosis)
treatment for CIM
anaemia - transfusions platelet transfusion cytoreductive therapy - HYDROXYCARBAMIDE (may worsen the anaemia) THALIDOMIDE BM transplant
