Condition- Myelofibrosis

Question 1

A mutation in which gene can lead to primary myelofibrosis?

Answer 1

JAK2 mutation

Question 2

State a cause of secondary myelofibrosis

Answer 2

radiation

Question 3

Explain the pahtological process which leads to the development of Myelofibrosis

Answer 3

1. Stem cell defect => megakaryocyte hyperplasia
2. Megakaryocytes release cytokines
3. Cytokines activate fibroblast proliferation
4. Fibriblasts deposit collagen in BM
5. Fibroblasts crowd out haematopoeitic stem cells => extra-medullary haematopoiesis

= Myelosclerosis

Question 4

State a cytokine that might be released by megakaryoctes which leads to fibroblast proliferation

Answer 4

Platelet Derived Growth Factor (PDGF)

Question 5

Describe the presenting symptoms of someone with Myelofibrosis

Answer 5

• Systemic symptoms (hypermetabolic symptoms)
  
  • FLAWS
  • Pruritus
• Symptoms of Extra-medullary haematopoiesis (splenomegaly)
  
  • Early satiety
  • Abdo discomfort (LUQ)
• Symptoms of osteosclerosis
  
  • Bone/ Joint pain
  • Hearing loss
• Symptoms of Anaemia, neutropenia
• Symptoms of thrombocytosis => DVT, PE

Question 6

List some of the signs of Myelofibrosis

Answer 6

Splenomegaly

Pallor

Question 7

What would you see in a FBC of someone with Myelofibrosis

Answer 7

• Low RBC
• Low WCC
• High Platelets
• High LDH + uric acid (increased metabolism)

Question 8

State a hallmark feature of Myelofibrosis on Blood film

Answer 8

Tear drop Poikilocytosis

Question 9

What would you see on bone marrow aspiration of someone with myelofibrosis? Which investigation would do after this?

Answer 9

BM aspiration => ‘Dry Tap’ unobtainable aspirate due to schlerosis

Would follow up with bone marrow biopsy

Question 10

Which test is diagnostic for Myelofibrosis? and what would you see?

Answer 10

Bone Marrow Biopsy

Fibrotic Hypercellular marrow