Chronic myeloproliferative disorders and chronic myeloid leukaemia

Question 1

What are chronic myeloproliferative disorders?

Answer 1

long term condition in which there is malignant proliferation of myeloid cells in the bone marrow

Question 2

What are the 3 main chronic myeloproliferative disorders?

Answer 2

Polycythaemia Vera
Essential thrombocytosis
Idiopathic Myelofibrosis
can lead to acute leukaemia

Question 3

What is Polycythaemia Vera?

Answer 3

bone marrow produces too many red cells
+/-neutrophils
+/-platelets
can be primary or secondary i.e. hypoxic, renal disease, drubs, congenital

Question 4

What is essential thrombocythaemia?

Answer 4

Increased platelets

Question 5

What is Myelofibrosis?

Answer 5

Variable cytopenias - reduction in the number of blood cells
with a large spleen

Question 6

What are the signs and symptoms of polycythaemia Vera?

Answer 6

Insidious
Itching (aquagenic- hot baths)
Plethoric face - red face
Headache, muzziness, 
General malaise
Tinnitus
Peptic ulcer
Gout - uric acid comes from the breakdown of RBC
Gangrene of the toes
Plethora - excessive blood
Engorged retinal veins
Splenomegaly

Question 7

How is polycythaemia Vera diagnoised?

Answer 7

Persistent increased Hb/hct >0.5
FBC
Ferritn
Epo level
UE/LFT

Question 8

What happens if there is a point mutation in the JAK tyrosine kinase?

Answer 8

diagnostic of myeloproliferative disorders
acquired
JH2 domain effected
DNA of that cell replicates & divides all the time

Question 9

What are the first line tests to detect Thrombocytosis?

Answer 9

FBC and film
Ferritin
CRP - C-reactive protein 
CXR
ESR - erythrocyte sedimentation rate

Question 10

What is the CALR mutation?

Answer 10

Calreticulin mutation
cell signalling protein produced in endoplasmic Reticulin
Mutation in EXON 9 of gene
Found in Myeloid progenitors
Mechanism of action unknown at present but may activate cell signal pathways

Question 11

What are the signs and symptoms of myelofibrosis?

Answer 11

Pancytopenia
B symptoms - fevers, night sweats, weight loss (10%)
Massive splenomegaly - takes over making the RBC. Pain, smaller appetite, frequency

Question 12

What investigations are done when suspecting myelofibrosis?

Answer 12

FBC and film
Haematinics - folates, iron, B12
Bone marrow results
JAK2 mutation
CALR mutation

Question 13

What is the acronym for causes of splenomegaly?

Answer 13

CHICAGO
Cancer
Haematological - Myelofibrosis, CML
Infection - Schistosomiasis,malaria
Congestion - Liver disease / portal
Autoimmune-  haemolysis
Glycogen storage disorders
Other - Amyloid, etc

Question 14

Out of Polycythaemia Vera, Essential thrombocytosis and Idiopathic Myelofibrosis, which is the most serious with the worst prognosis?

Answer 14

Idiopathic Myelofibrosis

Question 15

What are the characteristics for chronic myeloid leukaemia?

Answer 15

Leucocytosis+++
Leucoerythroblastic blood picture
Anaemia
Splenomegaly

Question 16

What are the symptoms and signs of chronic myeloid leukaemia?

Answer 16

Abdominal discomfort - Splenomegaly
Abdominal pain - Splenic infarction
Fatigue - Anaemia, catabolic state
Venous occlusion - Retinal vein, DVT, priapism
Gout - Hyperuricaemia

Question 17

What causes Chronic Myeloid Leukaemia?

Answer 17

Philadelphia chromosome

translational of chromosome 9 and 22 = oncogene