Myelofibrosis

Question 1

Define Myelofibrosis?

Answer 1

Disorder of haematopoietic stem cells characterised by progressive bone marrow fibrosis in associated with extramedullary haematopoiesis and splenomegaly

Question 2

What is the pathogenesis of Myelofibrosis?

Answer 2

Abnormal megakaryocytes release cytokines that stimulate fibroblast proliferation and collagen deposition in bone marrow
This results in extramedullary haematopoiesis in the spleen and liver

Question 3

What is the aetiology of Myelofibrosis?

Answer 3

Primary stem cell defect is UNKNOWN
It results in increased numbers of abnormal megakaryocytes with stromal proliferation secondary to growth factors released by megakaryocytes
30% of patients have a previous history of polycythaemia rubra vera or essential thrombocythaemia (overproduction of platelets by the bone marrow)

Question 4

What is the epidemiology of Myelofibrosis?

Answer 4

RARE

Peak onset: 50-70 yrs

Question 5

What is the most common presentation of Myelofibrosis?

Answer 5

ASYMPTOMATIC - diagnosed after routine blood counts

Question 6

What are some of the common systemic symptoms of Myelofibrosis?

Answer 6

Weight Loss 
Anorexia 
Fever 
Night Sweats 
Pruritis

Question 7

What are some of the Uncommon Systemic symptoms of Myelofibrosis?

Answer 7

LUQ pain 
Indigestion (due to massive splenomegaly)
Bleeding 
Bone pain 
Gout

Question 8

What are the signs of Myelofibrosis on physical examination?

Answer 8

Splenomegaly

Hepatomegaly (present in 50-60%)

Question 9

What investigations would you do for Myelofibrosis?

Answer 9

Bloods
Blood Film
Bone marrow aspirate or Biopsy

Question 10

What bloods would you do for Myelofibrosis?

Answer 10

FBC

LFTs - abnormal

Question 11

What would you look for specifically on a FBC for Myelofibrosis?

Answer 11

Initially variable Hb, WCC and platelets

Later stages leads to anaemia, leukopaenia, thrombocytopaenia

Question 12

What do you look for on a Blood Film for Myelofibrosis?

Answer 12

Leucoerythroblastic changes (red and white cell precursors in the peripheral blood)
'Tear Drop' poikilocyte red cells

Question 13

What do we see on a Bone Marrow Aspirate or Biopsy for Myelofibrosis?

Answer 13

Aspiration usually unsuccessful - ‘dry tap’ (due to fibrosis)
Trephine biopsy shows fibrotic hypercellular marrow, with dense reticulin fibres on silver staining