Myeloproliferative disorders

Question 1

What are the myeloproliferative disorders?

Answer 1

clonal haemopoietic stem cell disorders

Question 2

What is the difference ebtween MPD and acute leukaemia?

Answer 2

maturation is relatively preserved in MPD

Question 3

How are the myeloproliferative disorders broadly categorized?

Answer 3

BCR-ABL1 negative or positive

Question 4

What MPD is BCR-ABL positive?

Answer 4

chronic myeloid leukaemia

Question 5

Which MPDs are BCR-ABL negative?

Answer 5

idiopathic myelofibrosis; essential thrombocythaemia; polycythaemia rubra vera

Question 6

When should MPD be considered as a diagnosis?

Answer 6

when there are high counts without a reactive explanation, esp. a basophilia; thombosis in an unsual place; splenomegaly

Question 7

What is sene in the chronic phase of CML?

Answer 7

excess of mature neutrophils and some precurosors

Question 8

What is seen in the accelerated phase of CML?

Answer 8

proportion of mature cells compared to precurosors is dropping

Question 9

what is seen in the blast crisis phase of CML?

Answer 9

looks like AML- monomorphic

Question 10

What are the clinical features of CML?

Answer 10

splenomegaly; hypermetabolic symptoms; gout; increased viscosity problems- priapism etc.

Question 11

What is seen on blood coutn with CML?

Answer 11

normal/decreased Hb; leucocytosis with neutrophilia and myelocytes; eosinophilia; basophilia; thombocytosis

Question 12

What is the genetic abnormality in CML?

Answer 12

t(9:22)- Philidelphia chromsome

Question 13

What is the result of the philidelphia chromosome?

Answer 13

a new gene: BCR-ABL1

Question 14

What is the product of BCR-ABL1?

Answer 14

tyrosine kinase which causes abnormal phosphorylation (signalling)

Question 15

What is the treatment for CML?

Answer 15

imatinib

Question 16

What is polycythaemia rubra vera?

Answer 16

high Hb/hct accompanied by erythrocytosis (a true increase in red cell mass) but can have excessive production of otehr lineages

Question 17

What are causes of secondary polycythaemia?

Answer 17

chronic hypoxia; smoking; EPO-secreting tumour

Question 18

What are the causes of pseudopolycythaemia?

Answer 18

dehydration; diuretics; obesity

Question 19

What are the clinical features of PRV?

Answer 19

headache; fatigue; aqaugenic pruritis (warm water)

Question 20

What mutation is seen with PRV?

Answer 20

substitution in JAK2 resulting in loss of auto-inhibition

Question 21

What is JAK2?

Answer 21

a kinase

Question 22

What investigations should be done to look for secondary or pseudo causes of PRV?

Answer 22

CXR; O2 sats/ABGs; drug hx)

Question 23

What drug is implicated in pseudopolycythaemia?

Answer 23

testosterone

Question 24

What is the treatment for PRV?

Answer 24

venesect to hct <0.45; aspirin; cytotoxic oral chemo (hydroxycarbamide)

Question 25

What is essential thrombocythaemia?

Answer 25

uncontrolled production of abnormal platelets

Question 26

What are the results of abnormal platelet function?

Answer 26

increased thrombosis risk; hgih levels can also cause bleeding

Question 27

Why do ET patietns have a bleeding risk with lots of platelets?

Answer 27

acquired von Willebrand disease

Question 28

What are the causes of reactive thromobytosis?

Answer 28

blood loss; inflammation; malignancy; iron deficiency

Question 29

What disease should be excluded before ET is diagnosed?

Answer 29

CML- in early stages can just be a thrombocytosis

Question 30

What mutations are implicated in ET?

Answer 30

JAK2; CALR; MPL

Question 31

What is seen characteristicall on marrow with ET?

Answer 31

clusters of megakaryocytes

Question 32

What is the treatment for ET?

Answer 32

aspirin; cytoreductive therpay- hydroxycarbamide; anagrelide; IFN-alpha

Question 33

What are the causes of myelofibrosis?

Answer 33

idiopathic; post-polycythaemia or ET

Question 34

What is seen with idiopathyic myelofibrosis?

Answer 34

marrow failure; bone marrow fibrosis; extramedullary haemopoiesis; leukoerythroblastic film; tear-drop RBCs

Question 35

What is seen on bone marrow aspirate in myelofibrosis?

Answer 35

dry aspirate

Question 36

What mutations may be seen in myelofibrosis | ?

Answer 36

JAK2; CALR

Question 37

What are the causes of a leucoerythroblastic film?

Answer 37

reactive (sepsis); marrow infiltration; myelofibrosis

Question 38

What drugs are used in MF?

Answer 38

JAK2 inhibitors work on all MF patients, even wtihout JAK2 mutation