Chronic myeloproliferative disorders Flashcards
what are myeloproliferative disorders?
Clonal proliferation of haemopoeitic stem cells with increased production of one or more types of HSC
In contrast to acute - cell maturation is preserved
= proliferation of granulocytes/RBCs/Platelets
How are myeloproliferative disorders classified?
BCR-ABL1 positive - CML
BCR-ABL1 negative:
- polycythaemia rubra vera (RBCs)
- Essential thrombocytosis (platelets)
- idiopathic myelofibrosis
When should a MPD be considered?
high granulocyte count \+/- high RBC count \+/- high platelet count \+/- eosinophilia / basophilia \+ no reactive explanation
What features are common to myeloproliferative disorders? 5
Asymptomatic
Increased cellular turnover (gout, fatigue, weight loss, sweats)
Symptoms/signs due to splenomegaly
Marrow failure (fibrosis or leukaemic transformation:lower with PRV and ET)
Thrombosis (arterial or venous including TIA, MI, abdominal vessel thrombosis, claudication, erythromelalgia)
What is polycythaemia rubra vera? what is this important to distinguish from?
High haemoglobin/haematocrit accompanied by erythrocytosis (a true increase in red cell mass) but can have excessive production of other lineages
Important to distinguish from:
- secondary polycythaemia (chronic hypoxia,smoking, erythropoietin-secreting tumour etc)
- pseudopolycythaemia (eg dehydration,diuretic therapy, obesity)
What are the clinical features found in polycythaemia rubra vera?
Clinical features common to MPD
Headache, fatigue (remember blood viscosity raised NOT plasma viscosity)
Itch (aquagenic puritis)
What type of mutational analysis is part of the initial screening for polycythaemia rubra vera? what does this mutation cause?
JAK2: a kinase
JAK2 mutations present in over 95% of these patients
Mutation (substitution) results in loss of auto-inhibition
Activation of erythropoiesis in the absence of ligand
What is included in the investigation of polycythaemia rubra vera?
Investigation for secondary/pseudo causes (CXR, O2 saturation/arterial blood gases, drug history)
JAK2 analysis
Infrequent tests: erythropoietin levels, bone marrow biopsy
What is the treatment of polycythaemia rubra vera?
venesection to HCT<0.45 and aspirin
-if can’t tolerate give cytotoxic oral chemo (hydroxycarbamide but causes megaloblastic anaemia)
What is essential thrombocytosis? what is important to exclude?
Uncontrolled production of abnormal platelets
Platelet function abnormal
thrombosis
at high levels can also cause bleeding due to acquired von Willebrand disease
Exclude reactive thrombocytosis:
- blood loss
- inflammation
- malignancy
- iron deficiency
- CML
What are the clinical features of essential thrombocytosis?
Clinical features common to MPD (particularly vasoocclusive complications)
Bleeding (unpredictable risk especially at surgery)
What genetic mutations are found in essential thrombocytosis?
JAK2 mutations (in 50%)
CALR (Calreticulin) in those without mutant JAK2
MPL mutation
what is the treatment for essential thrombocytosis?
Anti-platelet agents
Aspirin
Cytoreductive therapy to control proliferation
hydroxycarbamide, anagrelide, interferon alpha
Myelofibrosis:
how can this arise?
Idiopathic(or agnogenic myeloid metaplasia)
Post-polycythaemia or essential thrombocythaemia
What happens in myelofibrosis?
abnormal fibrous deposition in the bone marrow = low blood count
