What are chronic myeloproliferative disorders?
long term condition in which there is malignant proliferation of myeloid cells in the bone marrow
What are the 3 main chronic myeloproliferative disorders?
Polycythaemia Vera
Essential thrombocytosis
Idiopathic Myelofibrosis
can lead to acute leukaemia
What is Polycythaemia Vera?
bone marrow produces too many red cells
+/-neutrophils
+/-platelets
can be primary or secondary i.e. hypoxic, renal disease, drubs, congenital
What is essential thrombocythaemia?
Increased platelets
What is Myelofibrosis?
Variable cytopenias - reduction in the number of blood cells
with a large spleen
What are the signs and symptoms of polycythaemia Vera?
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
How is polycythaemia Vera diagnoised?
Persistent increased Hb/hct >0.5 FBC Ferritn Epo level UE/LFT
What happens if there is a point mutation in the JAK tyrosine kinase?
diagnostic of myeloproliferative disorders
acquired
JH2 domain effected
DNA of that cell replicates & divides all the time
What are the first line tests to detect Thrombocytosis?
FBC and film Ferritin CRP - C-reactive protein CXR ESR - erythrocyte sedimentation rate
What is the CALR mutation?
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
What are the signs and symptoms of myelofibrosis?
Pancytopenia
B symptoms - fevers, night sweats, weight loss (10%)
Massive splenomegaly - takes over making the RBC. Pain, smaller appetite, frequency
What investigations are done when suspecting myelofibrosis?
FBC and film Haematinics - folates, iron, B12 Bone marrow results JAK2 mutation CALR mutation
What is the acronym for causes of splenomegaly?
CHICAGO Cancer Haematological - Myelofibrosis, CML Infection - Schistosomiasis,malaria Congestion - Liver disease / portal Autoimmune- haemolysis Glycogen storage disorders Other - Amyloid, etc
Out of Polycythaemia Vera, Essential thrombocytosis and Idiopathic Myelofibrosis, which is the most serious with the worst prognosis?
Idiopathic Myelofibrosis
What are the characteristics for chronic myeloid leukaemia?
Leucocytosis+++
Leucoerythroblastic blood picture
Anaemia
Splenomegaly
What are the symptoms and signs of chronic myeloid leukaemia?
Abdominal discomfort - Splenomegaly Abdominal pain - Splenic infarction Fatigue - Anaemia, catabolic state Venous occlusion - Retinal vein, DVT, priapism Gout - Hyperuricaemia
What causes Chronic Myeloid Leukaemia?
Philadelphia chromosome
translational of chromosome 9 and 22 = oncogene