Haematology 4: Myeloproliferative Disorders

Question 1

What are the main differences between myeloproliferative and myelodysplastic disorders ?

Answer 1

Myelodysplastic syndromes have ineffective differentiation whereas in myeloproliferative disorders the cells are normal and fully differentiated.

Question 2

Give 4 examples of chronic myeloproliferative disorders ?

Answer 2

Polycythaemia rubra Vera 
Essential thropmbocythaemia 
Idiopathic myelofibrosis
Idiopathic erythrocytosis
chronic granulocytic leukaemia

Question 3

List 4 signs/symptoms of Polycythaemia rubra Vera ?

Answer 3

Aquagenic pruritus- itch after having a warm bath
Gout
Engorged retinal veins
Erythromelalgia- Red painful extremities

Question 4

What levels would you expect in someone with Polycythaemia rubra Vera ?:

Hb :Low/High
Hct :Low/High
MCV: Low/High
EPO: Low/High

Answer 4

Hb: High
Hct: High
MCV: High
EPO: low (suppressed because of negative feedback)

Question 5

How is Polycythaemia rubra Vera diagnosed ?

Answer 5

Bone marrow biopsy- Increased cellularity, low EPO, Reticulin fibrosis

JAK2 V617F mutation is diagnostic

Question 6

What is pseudo polycythaemia ?

Answer 6

Reduced plasma volume in presence of a normal Hb conc.

Question 7

What causes Polycythaemia where EPO is raised ?

Answer 7

Hypoxia- High altitude
Renal disease
tumours

Question 8

What are the signs of Essential Thrombocythaemia ?

Answer 8

High platelet count
CVA
DVT/PE
Splenomegaly

Question 9

What are the signs of Chronic idiopathic myelofibrosis ?

Answer 9

FLAWS
anaemia
Thrombocytosis
Hepatosplenomegaly (massive, sites for extra medullary haematopoeisis)

Question 10

What is the characteristic finding of bone marrow aspiration in Chronic idiopathic myelofibrosis

Answer 10

Dry tap

Because of the fibrosis nothing comes out

Question 11

what two things are important in the control of haemopoiesis

Answer 11

growth factors (EPO)
receptors eg tyrosine kinase

Question 12

which kinases are important in myeloproliferative neoplasms

Answer 12

BCR-ABL kinases (feature of CML)
Janus KInases (JAK2)

Question 13

describe the JAK signalling pathway

Answer 13

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

Question 14

describe BCR-ABL negative myeloproliferative disorders

Answer 14

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

Question 15

clinical presentations of myeloproliferative disorders

Answer 15

thrombosis (arterial)
splenomegaly
haemorrhage

Question 16

difference between myeloproliferation, myelodysplasia and leukaemia

Answer 16

myeloproliferation = proliferation + full differentiation 
myelodysplasia = ineffective proliferation and differentiation 
leukaemia = proloferation and no/little differentiation

Question 17

what is polycythaemia vera

Answer 17

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

Question 18

clinical presentation of polycythaemia vera

Answer 18

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

Question 19

investigations for polythemia vera

Answer 19

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

Question 20

diagnostic test for PV

Answer 20

JAK2 V617F mutation
positive = PV (exon 14) or eryhtrocytosis (exon 12)
negaive = pseudopolycthaemia or true polycythaemia secondary to EPO/familial

Question 21

how is polycythaemia vera treated

Answer 21

reduce viscosity and keep HCT<45%
venesection
cytoreductive therapy
aspirin

Question 22

features of idiopathic erythrocytosis

Answer 22

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

Question 23

what is essential thrombocythaemia

Answer 23

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

Question 24

diagnosis of essential thrombocythaemia

Answer 24

platelets consistently > 600x10 9
megakaryocyte abnormalities
JAK 2 V617F mutation (in 50%)
splenomegaly mild
normal/slightly increased BM cellularity

Question 25

treatment for essential thrombocytaemia

Answer 25

aspirin
anagrelide
HYDROXYCARBAMIDE (main tx) - antimetabolite
alpha interferon

Question 26

what is chronic idiopathic myelofibrosis

Answer 26

clonal myeloproliferative disease with proliferation of megakaryocytes and granulocytes, associated with reactive BM fibrosis and extramedullary haemopoiesis
age >60

Question 27

presentation of chronic idiopathic myelofibrosis

Answer 27

incidental 
cytopaenias
thrombocytosis
splenomegaly (may be massive)
hepatomegaly 
hypermetabolic state - wt loss, fatigue, night sweats, hyperuricemia

Question 28

what are the stages of myelofibrosis

Answer 28

pre-fibrotic - mild blood changes, hypercellular marrrow

fibrotic - splenomegaly, blood changes, dry tap

Question 29

haematological findings of CIM

Answer 29

leucoerythroblastic picture
tear drop poikilocytes
giant platelets
circulating megakaryocytes

liver + spleen - extramedullary haemopoiesis

BM - dry tap, trephine biopsy (increased reticulin or collagen fibrosis)

Question 30

treatment for CIM

Answer 30

anaemia - transfusions
platelet transfusion
cytoreductive therapy - HYDROXYCARBAMIDE (may worsen the anaemia)
THALIDOMIDE 
BM transplant