Chronic Myeloproliferative Neoplasms

Question 1

A 60-year-old male presents with splenomegaly, headaches and dizziness. He has a background history of hypertension and congestive cardiac failure and is a smoker.

Give any three (3) potential causes of the raised haemoglobin (1½)

Answer 1

Diuretics, dehydration, smoking, Chronic lung disease, PV

Question 2

State the mainstay of treatment if the patient were diagnosed with polycythaemia vera (PV) (1)

Answer 2

Venesection

Question 3

Name the molecular abnormality that you would expect in PV and explain how this abnormality causes the disease (2)

Answer 3

JAK2 mutation. JAK2 is a tyrosine kinase that is involved in differentiation and proliferation of blood cells. If it is mutated this results in unregulated activation and transcription of genes that are responsible for proliferation of cells hence a myeloproliferative neoplasm (1½)

Question 4

A 65-year-old man presents with neurological symptoms of a stroke. His FBC shows: White cell count 15x10^9/l (normal range 13-17), Hb 21g/dl (13-17), Haematocrit 0.68 l/l (0.4-0.5), Platelet count 600x10^12/l (137-373)

Classify and give examples, of the causes of polycythaemia (½x6 = 3)

Answer 4

Primary:
Inherited - Familial
Acquired - Polycythemia Vera/ MPN

Secondary
Relative – dehydration
True – cardiorespiratory, renovascular, tumours producing EPO, abnormal Hb

Question 5

Name the common mutation that is implicated in the pathogenesis of the neoplastic form of polycythemia (1)

Answer 5

JAK2 mutation

Question 6

List two (2) important clinical complications of this disorder (½x2 = 1)

Answer 6

Thrombosis, Haemorrhage

Question 7

State the mainstay of therapy for the neoplastic form of polycythemia (1)

Answer 7

Venesection

Question 8

State two (2) complications of Polycythaemia Vera (½x2=1)

Answer 8

Thrombosis, Haemorrhage, Eventually fibrosis, Bone marrow failure