Myeloproliferative Neoplasms (MPN)

Question 1

what is MPN?

Answer 1

disorder of clonal HSCs with increased production of one or more types of haemopoietic cells
maturation is relatively preserved

Question 2

classification of MPN

Answer 2

1. BCR-ABL1 negative

2. BCR-ABL1 positive

Question 3

what is encompassed in BCR-ABL1 negative?

Answer 3

polycythaemia vera
essential thrombocythaemia
primary myelofibrosis

Question 4

what is encompassed in BCR-ABL positive?

Answer 4

CML

Question 5

what is CML?

Answer 5

chronic myeloid leukaemia= increased granulocytes due to philadelphia chromosome)

Question 6

define chronic myeloid leukaemia?

Answer 6

proliferation of myeloid cells (granulocytes, monocytes, platelets and RBCs)

Question 7

phases in CML

Answer 7

chronic phase

blast crisis

Question 8

presentation of CML

Answer 8

splenomegaly
hypermetabolic symptoms= gout
hyperleukocytosis and priapism

Question 9

diagnosis of CML

Answer 9

FBC
hypercellular bone marrow
philadelphia chromosome

Question 10

what does the FBC in CML show?

Answer 10

leucocytosis with neutrophilia and myeloid precursors, eosinophilia, basophilia

Question 11

what is the philadelphia chromosome?

Answer 11

chromosome 9 and chromosome 22 trade parts

Question 12

what does the philadelphia chromosome cause in CML?

Answer 12

chromosome 22 now contains BCR-ABL1 gene which causes phosphorylation

Question 13

how to distinguish reactive changes

Answer 13

only neutrophil count raised
plasma viscosity
CRP

Question 14

management of CML

Answer 14

tyrosine kinase inhibitors e.g. imatinib

blast crisis is fatal so may need transplant

Question 15

features common to BCR-ABL1 negative

Answer 15

>65
often asymptomatic
increased cellular turnover
splenomegaly
marrow failure
thrombosis

Question 16

increased cell turnover

Answer 16

gout
fatigue
weight loss
sweats

Question 17

what is polycythaemia vera (PV)?

Answer 17

erythrocytosis causing high Hb and Hct

Question 18

what does PV need to be distinguished from?

Answer 18

• secondary polycythaemia

- pseudo-polycythaemia

Question 19

causes of secondary polycythaemia

Answer 19

chronic hypoxia (COPD)
smoking
EPO-secreting tumour

Question 20

causes of pseudo-polycythaemia

Answer 20

dehydration
diuretics
obesity (reduced plasma, normal red cell mass)

Question 21

presentation of PV

Answer 21

features common to MPN
headache, fatigue, blood viscosity raised
itch (aquagenic pruritis- itchy after a hot bath)

Question 22

diagnosis of PV

Answer 22

splenomegaly
JAK2 mutation
investigations for other causes

Question 23

what is the JAK2 mutation?

Answer 23

mutated kinase with loss of auto-inhibition causing activation of erythropoiesis

Question 24

investigations for other causes of polycythaemia

Answer 24

CXR
O2 saturation
DH
EPO levels

Question 25

management of PV

Answer 25

mainly to stop thrombus formation: - venesect to Hct <0.45 - aspirin - cytotoxic oral chemotherapy e.g. hydroxycarbamide

Question 26

what is essential thrombocythaemia?

Answer 26

uncontrolled production of abnormal platelets

Question 27

what does essential thrombocythaemia cause?

Answer 27

thrombosis | acquired VWD

Question 28

why does ET cause acquired VWD?

Answer 28

platelets absorb VWF

Question 29

presentation of ET

Answer 29

vaso-occlusive complications e.g. black toe | bleeding

Question 30

diagnosis of ET

Answer 30

FBC | genetics= JAK2, CALR, MPL, some are triple negative

Question 31

management of ET

Answer 31

antiplatelets e.g. aspirin | cytoreductive therapy to control proliferation e.g. hydroxycarbamide, anagrelide, IFN-alpha

Question 32

what is myelofibrosis?

Answer 32

bone marrow fibrosis and extramedullary haematopoiesis

Question 33

presentation of MF

Answer 33

marrow failure (anaemia, infection, bleeding) splenomegaly (LUQ pain, portal hypertension) hypercatabolic

Question 34

diagnosis of MF

Answer 34

blood film dry aspirate or fibrosis on trephine biopsy JAK2, CALR, MPL or triple negative

Question 35

what does the blood film show in MF?

Answer 35

leucoerythroblastic + teardrop RBCs

Question 36

other causes of leucoerythroblastic blood film

Answer 36

sepsis | marrow infiltration

Question 37

management of MF

Answer 37

blood transfusion, platelet transfusions, antibiotics allogenic stem cell transplant in some splenectomy JAK2 inhibitors

Question 38

why are more measures taken in MF?

Answer 38

more aggressive