Myeloproliferative disorders

Question 1

what does marrow have

Answer 1

granulocytes
red cells
platelets

Question 2

what kind of disorders are myeloproliferative disorders

Answer 2

clonal haemopoietic stem cell disorders with an increased poduction of one or more cell types of haemopoietic cells

Question 3

difference between myeloproliferative disorders and acute leuk

Answer 3

maturation is relatively preserved

Question 4

classification of MPD

Answer 4

BCR-ABL1 pos:
chronic myeloid leuk - over production of granulocytes. philadelphia chromosome

BCR-ABL1 neg:
idiopathic myelofibrosis - scarring of th bone marrow and fibrosis
polycythaemia ruba vera -pver poroduction of red cells
essential thrombocytopenia - over production of platelets

Question 5

when is MPD considered

Answer 5

high granulocyte +/- high red cell count/Hb +/- high platelet count +/- eosinophilia/basophilia

splenomegaly
thrombosis in an unusual place

no reactive explanation for any of these

Question 6

what is chronic myeloid leuk

Answer 6

prolif of myeloid cells - grnaluocytes and their precursors and other lineages (platelets)

Question 7

why is CML fatal

Answer 7

fatal without stem cell/bone marrow transplantation in the chronic phase

Question 8

phases of CML

Answer 8

chronic phase with intact maturation for 3-5 years
accelerated phase
blast crisis - reminiscent of acute leuk with maturation defect

Question 9

CML clinical features

Answer 9

asymp
splenomegaly - get full quick
hyper metabolic symptoms - gout, bone pain, sweats
misc: problems related to hyperleucocytosis problems, priapism

Question 10

lab features of CML

Answer 10

normal/decreased Hb
leucocytosis with neutrophilic and myeloid precursors (myelocytes), eosinophilia, basophilia
thrombocytosis

Question 11

marrow of CML

Answer 11

increase in neutrophils, myelocytes, eosinophils, basophils and basophil precursors

Question 12

hallmark of CML

Answer 12

philadelphia chromosome
reciprocal translocation between 9 and 22
Leads to a new mixture of genes called BCRABL

Question 13

genetics of CML

Answer 13

BCR-ABL1 produces tyrosine kinase which causes abnormal phosphorylation which leads to haematological changes in CML

Question 14

genetics of CML and treatment

Answer 14

durable disease responses with tyrosine kinase inhibitor - imatinib

Question 15

features of neg MPD

Answer 15

asymp
gout, fatigue, weight loss
splenomegaly
marrow failure - fibrosis or leukaemia transfusion
thrombosis

Question 16

what can marrow failure lead to

Answer 16

acute leuk state

Question 17

PRV is what

Answer 17

high hb and haematocrit
erythrocytosis
dominant effect is on red cells but can have an increased platelet count

Question 18

secondary polycythaemia

Answer 18

chronic hypoxia
smoking
erythropoietin secreting tumour

Question 19

pseudopolycyhtaemia

Answer 19

dehydration
diuretic therapy
obesity

Question 20

true polycythaemia

false polycythaemia

Answer 20

red cell has increased

plasma has shrunk giving the impression that the Hb is high but it actually isn’t

Question 21

PRV clinical features

Answer 21

common to MPD
headache, fatigue (remember blood viscosity has increased not plasma viscosity)
itch (aquagenic pruritus) - after a shower

Question 22

investigation of polycythaemia

Answer 22

history
exam - people with secondary poly won’t have splenomegaly
FBC, film
JAK2 mutation status

Question 23

JAK2 is what

Answer 23

kinase
present in over 95%of PRV px
mutation results in loss of auto inhibition
activation of erythro all the time

part of initial screening

Question 24

treatment of PVR

Answer 24

venesct to haemocrit to <0.45
aspirin - reduce thrombotic risk
cytotoxic oral chemo - hydroxycarbamide

Question 25

essential thrombocytopenia

Answer 25

uncontrolled production of abnormal platelets

thrombosis
at high levels can cause bleeding due to acquired von willebran disease

Question 26

clinical features of ET

Answer 26

similar to MPD esp vasooclusive complications

bleeding

Question 27

ET dx

Answer 27

exclude reactive thrombocytosis - blood loss, inflam, malig, iron defic

exclude CML

genetics :
JAK2 (in 50%)
CALR in those without mutant JAK2
MPL mutation

bone marrow

Question 28

ET treatment

Answer 28

anti platelet - aspirin

cytoreductive therapy to control prolif - hydroxycarbamide, anagrelide, interferon alpha (last line)

Question 29

myelofibrosis

Answer 29

idiopathic
secondary:
post polycthaemia or ET which progresses to marrow failure

Question 30

IM features

Answer 30

marrow failure 
bone marrow fibrosis 
extra medullary haematopoiesis (liver and spleen)
leukocerythoblastic film appearance 
teardrop shaped RBCs in peripheral blood

Question 31

IM clinical features

Answer 31

marrow failure - anaemia, bleeding, infection
splenomegaly - LUQ pain, complication such as portal htn

hyper catabolism - anorexia, weight loss

features of MPD

Question 32

IM lab dx

Answer 32

typical blood film - tear drop RBC and leucoerythroblastic

dry aspirate

fibrosis on trephine biopsy

JAK2 or CALR mutation

Question 33

causes of leucoerythroblastic

Answer 33

reactive - sepsis
marrow infiltration - cancer
myelofibrosis

Question 34

IM rx

Answer 34

supportive care - blood transfusion, platelets, ABs

allogeneic stem cell trabsplantion in a few px <50s

splenectomy - controversial

JAK2 inhibitors - improve spleen size, quality of life and possibly survival

Question 35

high white cell count

Answer 35

infection
post surgery
steroids

Question 36

high platelets

Answer 36

infection 
iron defic
malig
blood loss
splenectomy

Question 37

high red cells

Answer 37

dehydration - diuretics
pseudoplycythaemia
secondary polycythaemia - hypoxia induced etc