40 Myeloproliferative disorders + CML Flashcards
Name the three myeloproliferative disorders.
Polycthaemia vera.
Essential thrombocytosis.
Idiopathic fibrosis.
What is the blood abnormality in polycythaemia vera?
Increased RBCs ± increased neutrophils and platelets.
What are the clinical features of polycythaemia vera? (8).
Insidious. Itching. Plethoric face. Headache and general malaise. Tinnititus. Peptic ulcer. Gout. Engorged retinal veins. Splenomegaly.
Which tests are used to distinguish between the different types of polycythaemia? (4).
FBC.
Ferritin.
Epo (erythropoietin) level.
U&Es/LFTs.
How is 1o polycythaemia differentiated from 2o?
1o: RBC production with low EPO.
2o: EPO raised.
Name five causes of secondary polycythaemia:
Any central hypoxic process. Renal disease. EPO producing tumour. Drug associated (androgens, post renal transplant). Congenital.
Which tests should be done in polycythaemia vera? (3).
JAK2 mutation.
Bone marrow examination.
EXON12 mutation.
What is the JAK2 mutation?
Nucleotide?
Amino acid?
Mechanism?
In JH2 domain (inactive).
G-T mutation at nucleotide 1849.
V617F (phenylalanine for valine ar 617).
Destroys BsaXI site.
What does the JAK2 mutation do? (2)
Promotes cell division.
EPO no longer needed to turn on EPO receptors.
What is the JAK2 mutation diagnostic of?
A myeloproliferative disorder.
What is the treatment for polycythaemia vera?
Risks?
Survival?
Venesection, aspirin.
Progression to AML and myelofibrosis.
15 years.
What is thrombocytosis?
Increased platelets.
What are the causes of thrombocytosis?
1o: essential.
2o: reactive (surgery, infection, malignancy, low iron, hyposplenism, haemolysis, drug).
What are the 1st and 2nd line investigations for thrombocytosis?
1: Blood film, ferritin,CRP, CXR, ESR.
2: JAK and CALR mutations.
What is the CALR mutation?
What does it do?
Who is it found in?
Calreticulin mutation in exon 9 of gene.
Activates cell signalling pathways.
+ve in 90% of JAK2 -ve essential thrmobocytosis.
