Chronic myeloproliferative disorders and chronic myeloid leukaemia Flashcards
What are chronic myeloproliferative disorders?
- Malignant clonal stem cell disorders of the bone marrow.
- Polycythaemia Vera
- Essential thrombocytosis
- Idiopathic Myelofibrosis
What percentage of chronic myeloproliferative disorders transform into acute leukaemia?
10%
What is polycythaemia vera?
- Increased red cells, +/-neutrophils, +/-platelets
- Distinguish from secondary polycythaemias and relative polycythaemia
What is essential thrombocythaemia?
- Increased platelets
- Distinguish from reactive thrombocytosis
What is myelofibrosis?
- Variable cytopenias with a large spleen
- Distinguish from other causes of splenomegaly
What is the epidemiology of polycythaemia vera?
All ages, peak at 50-70 years
What are the signs and symptoms of polycythaemia vera?
- Itching (aquagenic- hot baths)
- Plethoric face
- Headache, muzziness,
- General malaise
- Tinnitus
- Peptic ulcer
- Gout
- Gangrene of the toes
- Engorged retinal veins
- Splenomegaly
How is polycythaemia vera diagnosed?
- Persistent increased Hb/hct >0.5
- Is it:
- relative V absolute polycthaemia
- Primary V Secondary polycythaemia
- Detailed History and Examination
- 1st line tests
- FBC
- Ferritn
- Epo level
- UE/LFT
What is the cause if primary polycythaemia?
Polycythaemia vera
What are the causes of secondary polycythaemia?
Central hypoxic process
- Chronic lung disease
- Right-to-left shunts Heart Disease
- Carbon monoxide poisoning
- Smoker
- High Altitude
Renal disease
EPO production Tumours
Drug associated
- Treatment with androgen preparations
- Postrenal transplant erythrocytosis
Congenital
- High oxygen-affinity haemoglobin
- Erythropoeitin receptor-mediated
Idiopathic erythrocytosis
What second line tests should be performed in cases of suspected polycythaemia?
Epo elevated
- CXR
- ABG
- USS abdomen
Epo normal or low
- JAK2 mutation
- Bone marrow examination
- EXON12 mutation
For which cytokine receptors is JAK the signalling pathway?
GM-CSF GCSF EPO TPO SCF interleukins
What are the features of the JAK2 mutation?
- Occurs in the JH2 domain (inactive)
- G-to-T mutation at nucleotide 1849
- Phenylalanine for valine at 617 in protein (V617F)
- Destroys a BsaXI site
- Patients may be heterozygous or homozygous
The presence of a JAK2 V617F mutation
in peripheral blood DNA is diagnostic of what?
A myeloproliferative disorder?
What is the treatment of polycythaemia vera?
- Venesection - aim for a haematocrit of
What is the prognosis for polycythaemia vera?
- Good - 15 year median survival
- Risk developing AML
- Risk developing Myelofibrosis
What is primary essential thrombocytosis (ET)?
A disease in which abnormal cells in the bone marrow cause an increase in platelets.
What is reactive thrombocytosis?
An elevated platelet count (> 450,000/μL) that develops secondary to another disorder.
What are the causes of reactive thrombocytosis?
- Surgery
- Infection
- Inflammation
- Malignancy
- Iron deficiency
- Hyposplenism
- Haemolysis
- Drug induced (steroids, adrenaline, TPO mimetics)
- Rebound post chemo
How would you perform a thrombocytosis investigation?
- Good history / examination IMPORTANT (e.g.recent normal count prior to surgery)
- Persistent Platelets >450 x109/L
1st line investigations
- FBC and film
- Ferritin
- CRP
- CXR
- ESR
What second-line investigations would you perform in suspected thrombocytosis?
- JAK2
- CALR
- ? Bone marrow biopsy
- Extensive search for secondary cause
What is the CALR mutation?
- Calreticulin mutation
- cell signalling protein produced in ER (endoplasmic Reticulin)
- Mutation in EXON 9 of gene
- Found in Myeloid progenitors in ET
- Mechanism of action unknown at present but may activate cell signal pathways
- found in upto 90% of JAK2 negative ET
What percentage of ET patients have a JAK2 mutation?
50%
What percentage of ET patients have a CALR mutation?
45%
