myeloproliferative disorders

Question 1

define: myeloproliferative disorders

Answer 1

disorder of the common myeloid progenitor

growth factors specific for each lineage, tyrosine kinase plays a important role in abnormal haematopoiesis

Question 2

Kinases in myeloproliferative neoplasms

Answer 2

BCR-ABL (in cml) need imatinib

Janus kinases - a family of trk associated growh factors.

growth factors interact with receptor, comformational change, phosphorylation ofJAK2 leads to activation of STAT pathway –> proliferation overproduction of mature cells

Question 3

features of BCR-abl -ve chronic MPN

Answer 3

overproduction of one or more mature myeloid ceullular elements

increase of fibtrosis in BM

can progress to acute leukaemia like picture (10+ years)

spontaneous colony growth without EPO/TPO

commonly thrombosis (arterial)

splenomegaly

Polycythaemia vera, essential thrombocythaemia, idiopathic myleofibrosis

Question 4

difference between leukaemia , myelodysplasticS, myeloproliferative

Answer 4

leukaemia porliferation without differentiation

mds ineffective proliferation and differentiation

mpn proliferation and full differentiation

Question 5

what is PV

Answer 5

increase in production of red blood cells

independent of normal erythropoeitin

true increase in plasma volume ( compensatory)

increase platlets + granulocytic cells

Question 6

presentation of PV

Answer 6

hyperviscosity

headaches light headed stroke

visual disturbance

fatigue dyspnoea

increase histamine release

aquagenic pruritus (itch after bath)

peptic ulceration (with chronic bleeding iron deficient)

variable splenomeagaly high haematocrit + splenomegaly

plethora (red)

erythromelalgia: red painful extremities
gout: increase red cell turn over

Question 7

engorged veins in retina

gout

erythromelalgia

Answer 7

polycythaemia vera

Question 8

PV investigations

Answer 8

increase haemoglobin + haematocrit

platlet may be increased

white cells increase/normal

no immature cells

increase blood volume (isotype dilution)

Bone marrow: increased cellularity

low serum erythropoitetin

JAK 2 V617F mutation present (diagnostic)

Question 9

bone marrow trephine

Answer 9

all marrow occupied by cells, mostly mature cells in PV

Question 10

what is pseudopolycythaemia?

Answer 10

high haematocrit decrease in plasma so no real increase in RBC mass

normal (38-50M 35-45F)

Question 11

raised haematocrit next investigation?

Answer 11

Look for jak2 v617 +ve –> polycythaemia vera (exon 14)

exon12 mutation only red cells (no platelets or white cells)–> erythrocytosis

Jak2 negative –> true polycythaemia secondary to increase EPO hypoxia/renal disease tumours , familial

or pseudopolycythaemia

Question 12

PV diagnostic criteria

Answer 12

old criteria : RCM>25% of mean

increase Hb

current criteria: increase red cell production + mutation jak2 v617

Question 13

PV treatment

Answer 13

reduce viscosity HCT<45% venesection, cytoreductive therapy (reduce haematopoiesis

reduce risk of thrombosis aspirin keep platlets low below 400x10^9

Question 14

idiopathic erythrocytosis features

Answer 14

isolated erythrocytosis

low EPO

less likely to transform to AML or get myelofibrosis

absense of jak2 617 but can get exon 12 mutation of jak2 gene

venesection

better prognosis

Question 15

define: essential thrombocytopenia

Answer 15

MPN involving megakaryocytic lineage

platlet acocunt above 600x10^9/L

sustained thrombocytosis

peaks 55 and 30

females mostly 2nd peak

jak2 v617 in 50%

Question 16

Essential thrombocytopenia presentation

Answer 16

thrombosis CVA gangrene tia, dvt, pe

bleeding mucous membrane (parodoxical)

headahces dizziness

modest splenomegaly

Question 17

ET bone marrow

Answer 17

more fat spaces than PV but clustering of megakarytocytes

Question 18

ET treatment and who to treat

Answer 18

aspirin (thrombosis)

anagrelide ( decrease platlet , 2nd line , accelerate myelofibrosis)

low risk age<40 platlet <1500 asymptomatic

high risk >60 age platelet >1000

thrombotic symptoms

normal life span

Question 19

proliferation of megakaryocytes (fibrosis) in marrow and granulocytic cells

anaemia and thrombocytosis

disease of older patients and extramedullary haematopoesis

jak2 50%

Answer 19

chronic idiopathic myelofibrosis (primary)

can get massive splenomegaly (buddchiari syndrome abdopain ascites liver enlargement occulsion of hepatic vein) ,hepatomegaly and hypermetabolic state (weight loss, fatigue, night sweats, hyperuricaemia

Question 20

myelofbirosis prefibrotic stage

Answer 20

may be confused with ET mild blood changes, hypercellular marrow

Question 21

myelofibrosis fibrotic stage

Answer 21

splenomegaly blood changes

dry tap bone marrow prominenet fibrosis

osteosclerosis

blood : leukoerythroblastic picture nucleated red cells and promyelocytes

tear drop poikilocytes

giant platelets

circulating megakaryocytes

extramedulary haematopoiesis (spleen liver)

Question 22

chronic idiopathic myelofibrosis treatment :

Answer 22

anaemia

platelets often ineffective

splenectomy

cytoreductive hydroxycarbamide but can increase anaemia

thalidomide can improve

bone marrow transplant in young patients