Myeloproliferative Disorders

Question 1

what are myeloproliferative disorders?

Answer 1

group of haematopoietic stem cell conditions occurring due to uncontrolled proliferation of a single type of stem cell

Question 2

what do all types of myeloproliferative disorder have in common?

Answer 2

all have mutations which continuously activate JAK2

Question 3

what is JAK2?

Answer 3

enzyme which stimulates production of RBCs, WBCs and platelets
usually only activated when additional blood cell production needed such as during inflammation, hypoxia or certain blood malignancies

Question 4

are myeloproliferative disorders considered cancer?

Answer 4

yes

type of bone marrow cancer

Question 5

what genetic mutations can be associated with myeloproliferative disorders?

Answer 5

JAK2
MPL
CALR

Question 6

possible complication of myeloproliferative disorders?

Answer 6

have potential to progress and transform into acute myeloid leukaemia (AML)

Question 7

types of myeloproliferative disorders?

Answer 7

primary myelofibrosis
polycythaemia vera
essential thrombocythaemia

Question 8

what is myelofibrosis?

Answer 8

least common and most aggressive myeloproliferative disorder

where proliferation of the cell line leads to fibrosis of the bone marrow (bone marrow replaced by scar tissue)

Question 9

what can cause myelofibrosis?

Answer 9

can occur on its own (primary myelofibrosis)

can be result of progression from polycythaemia vera or essential thrombocythaemia

Question 10

what happens in myelofibrosis?

Answer 10

proliferation of cell line
proliferating cells release cytokines such as fibroblast growth factor causing fibrosis of bone marrow
fibrosis affects production of blood cells and can lead to anaemia, low WBCs etc

Question 11

possible complications of myelofibrosis?

Answer 11

when bone marrow is replaced by scar tissue, blood cell production starts to happen in other places such as liver and spleen (extra-medullary haematopoiesis) leading to hepatosplenomegaly
this can cause portal hypertension or spinal cord compression if it occurs around the spinal cord

Question 12

possible symptoms of myelofibrosis?

Answer 12

can have hepatomegaly or splenomegaly or both
can have portal hypertension
variable changes in RBC, WBC and platelet count
can have symptoms of spinal cord compression

Question 13

FBC features of myelofibrosis?

Answer 13

anaemia
can have high or low WBCs (leukocytosis or leukopaenia)
can have high or low platelets (thrombocytosis or thrombocytopenia)

Question 14

blood film features of myelofibrosis?

Answer 14

teardrop shaped RBCs
varying sizes of RBCs (poikilocytosis)
immature RBCs and WBCs (blast cells)

Question 15

possible complications of myelofibrosis?

Answer 15

can progress to AML

Question 16

how is myelofibrosis managed?

Answer 16

can just be monitored if mild disease
allogenic stem cell transplant (can cure but carries risks)
chemo (can control disease and help symptoms but not curative)
supportive management of anaemia, splenomegaly, portal hypertension etc

Question 17

what is polycythaemia vera?

Answer 17

result of proliferation of erythroid cell line (excessive production of normal RBCs)

Question 18

which is the most common myeloproliferative disorder?

Answer 18

polycythaemia vera

Question 19

3 key signs of polycythaemia vera on examination?

Answer 19

conjunctival plethora (very red as lots of RBCs unlike anaemia where theyd be pale)
ruddy complexion
splenomegaly (as spleen filters RBCs)

Question 20

blood features of polycythaemia vera?

Answer 20

increased RBC production

raised Hb

Question 21

complications of polycythaemia vera?

Answer 21

arterial or venous thrombosis due to hyperviscosity as a result of increased RBCs
TIAs
migraine
aquagenic pruritis
bleeding or pseudohyperkalaemia (due to extreme thrombocytosis)
splenomegaly
can transform into myelofibrosis which can cause bone marrow failure and acute leukaemia

Question 22

how is polycythaemia vera managed?

Answer 22

venesection = first line
aspirin can reduce risk of blood clots
chemo can help control proliferation

Question 23

what is essential thrombocythaemia?

Answer 23

proliferation of the megakaryocyte line (platelets)

Question 24

blood features of essential thrombocythaemia?

Answer 24

increased platelets (thrombocytosis) alone - usually have platelet count >600

Question 25

diagnosis of essential thrombocythaemia?

Answer 25

diagnosis of exclusion
thrombocytosis is common in all myeloproliferative disorders but if thats the only abnormality then its probs essential thrombocythaemia

Question 26

complications of essential thrombocythaemia?

Answer 26

TIA
migraine
burning pains in hands and feet
bleeding or pseudohyperkalaemia
can have thrombosis or splenomegaly but rare
some patients can progress to myelofibrosis - bone marrow failure or AML

Question 27

lifespan in essential thrombocythaemia?

Answer 27

normal

Question 28

how is essential thrombocythaemia managed?

Answer 28

aspirin can reduce clot risk

chemo can control disease

Question 29

test of choice for diagnosing myeloproliferative disorders?

Answer 29

bone marrow biopsy
(cant really do bone marrow aspiration as bone marrow is “dry” due to fibrosis)
can also do genetic testing for JAK2, MPL and CALR genes