Myelofibrosis

Question 1

Definition

Answer 1

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

Question 2

Pathogenesis

Answer 2

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

Question 3

Aetiology

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

Epidemiology

Answer 4

• RARE

* Peak onset: 50-70 yrs

Question 5

Presenting symptoms

Answer 5

• ASYMPTOMATIC - diagnosed after routine blood count
• Systemic Symptoms

o COMMON:
• Weight loss
• Anorexia
• Fever
• Night sweats
• Pruritis

o UNCOMMON:
• LUQ pain
• Indigestion (due to massive splenomegaly)
• Bleeding
• Bone pain
• Gout

Question 6

Signs on physical examination

Answer 6

• SPLENOMEGALY

* Hepatomegaly (present in 50-60%)

Question 7

Investigations (bloods)

Answer 7

o FBC
• Initially variable Hb, WCC and platelets
• Later stages –> anaemia, leukopaenia, thrombocytopaenia

o LFTs - abnormal

Question 8

Investigations (blood film)

Answer 8

o Leucoerythroblastic changes (red and white cell precursors in the peripheral
blood)

o ‘Tear drop’ poikilocyte red cells

Question 9

Investigations (biopsy)

Answer 9

Bone Marrow Aspirate or Biopsy

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