Myelofibrosis

Question 1

Define Myelofibrosis

Answer 1

Disorder of haematopoietic stem cells characterised by abnormal production of RBCs, White cells and platelets in association with marrow fibrosis and extramedullary haematopoiesis

(Bone marrow replaced with connective tissue)

Question 2

Aetiology of Myelofibrosis

Answer 2

Primary myelofibrosis is due to gene mutation in haematopoietic cells which stimulates the JAK-STAT pathway -> cells mature and divide rapidly -> megakaryocytes-> release cytokines -> increase fibroblast GF -> fibrosis -> scarring of bone marrow -> haematopoietic cells migrate to the liver, spleen and lungs

Associations: Radiation, Benzene

Secondary develops from thrombocythemia and polycythaemia vera

Question 3

Symptoms of Myelofibrosis

Answer 3

May be asymptomatic

Constitutional symptoms: weight loss, fever, night sweats
Pulmonary hypertension: SOB, fatigue, presyncope
Joint and bone pain (due to osteosclerosis)
Hearing loss (due to otosclerosis)
Bleeding: petechiae, GI bleeding
Recurrent infections
Pruritis
LUQ pain, indigestion (splenomegaly)

Question 4

Signs of Myelofibrosis

Answer 4

MASSIVE Splenomegaly
Hepatomegaly
Portal hypertension signs: Visible veins, ascites, splenomegaly
Pulmonary hypertension

Question 5

Investigations for Myelofibrosis

Answer 5

Blood film: Tear drop poikilocyte red cells
Bone marrow aspirate or biopsy: Dry Tap (aspiration unsuccessful), biopsy shows fibrotic hypercellular marrow (marrow fibrosis) with dense reticulin fibres on silver staining

FBC: anaemia, leukocytes variable, Potential pancytopenia 
LFTs: abnormal
CD34+ cell count: elevated
Antinuclear antibodies: elevated
Rheumatoid factor titre: elevated
Complement levels: activation
Coomb's: positive