Myeloproliferative disorders

Question 1

What are the myeloproliferative disorders?

Answer 1

Clonal haematopoeietic stem cell disorders

Polycythaemia Vera
Essential Thrombocythaemia
Myelofibrosis
(CLL)

there is a lot of cross-over between the MPDs

Question 2

What is the mutation common to the MPDs and what does it do?

Answer 2

JAK2 mutation (in varying %)
- codes for autophosphorylation of tyrosine kinase (constantly switched on)

if mutation present in RBCs -> PCV
platelets -> ET
reticulin -> myelofibrosis

Question 3

What are the features of PCV?

Answer 3

increase in red cell mass
- increase Hb and HCT
splenomegaly

Question 4

What is the % of PCV that are JAK2 +?

Answer 4

90%

Question 5

What is the management of PCV?

Answer 5

venesection

increased thrombotic risk -> aspirin

Question 6

What are the complications of MPDs?

Answer 6

thrombotic risk
progression on to myelofibrosis
progression on to AML

Question 7

What is the most common MPD?

Answer 7

ET

Question 8

what are the features of ET?

Answer 8

blood film: thrombocytosis

• plts > 450
  marrow: increased numbers of megakaryocytic

Question 9

What are the diagnostic criteria for ET?

Answer 9

plts > 450
BM characteristic
NOT
- iron deficient 
- other MPD
JAK2+ or absence of reactive thrombocytosis if JAK2 neg

Question 10

What is the treatment for ET?

Answer 10

Aspirin (thrombotic risk)
Hydroxyurea
- suppresses bone marrow

Question 11

What are the features of myelofibrosis?

Answer 11

increase in fibrous material in bone marrow occupying space
- leukoerythroblastic picture on blood film
- immature red and white cells
splenomegaly
often thrombocytosis (cross-over with ET)

Question 12

What is the differential diagnosis for a leukoerythroblastic blood film?

Answer 12

Myelofibrosis
bone marrow infiltration
- infection e.g. TB
- malignancy e.g. breast

Must do a BM biopsy if this is seen

Question 13

What is the treatment for myelofibrosis?

Answer 13

• observation
• aspirin
• hydroxyurea if thrombocytosis
• allogeneic SCT if progressive MF (splenomegaly, marrow failure) or early leukaemia change

Question 14

What are Calreticulin mutations seen in?

Answer 14

40% ET
40% MF
- significant cross-over between these two MPDs

Question 15

What JAK2 inhibitors are available and what are their effects?

Answer 15

Ruxolitinib

improve constitutional symptoms significantly but no biological response
- no change to bone marrow or blood counts

also have same effect in JAK2 negative MPDs

Question 16

What mutations are present in MF?

Answer 16

50% JAK2+

40% Calreticulin +

Question 17

What can happen to the spleen in ET or PCV?

Answer 17

auto-infarction

also occurs in sickle cell