Myeloproliferative Neoplasms Flashcards
what are myeloproliferative neoplasms
Clonal haemopoietic stem cell disorders with an increased production of one or more types of haemopoietic cells
chronic myeloid leukaemia has mostly overproduction of _______
granulocytes
polycythaemia - overproduction of ______
RBCs
when to consider an MPN
High Granulocyte count
and/or
High Red cell count / haemoglobin
and/or
High Platelet count
and/or
Eosinophilia/basophilia
Splenomegaly
Thrombosis in an unusual place
AND NO REACTIVE EXPLANATION
which chronic condition leads to chronic hypoxia and Secondary erythrocytosis
COPD
chronic myeloid leukaemia phases
- chronic phase (3-5 years?)
- accelerated phase (transition to maturation defect)
- blast crisis
CML clinical features
Asymptomatic
Splenomegaly
Hypermetabolic symptoms
Gout
Misc: Problems related to hyperleucocytosis problems, Priapism
CML laboratory features - blood count changes
normal/↓Hb
leucocytosis with neutrophilia and myeloid precursors (myelocytes), eosinophilia, basophilia
thrombocytosis
___________ chromosome is the hallmark of CML
philadelphia
CML - Philadelphia chromosome results in a new gene: ________
BCR-ABL-1
CML treatment
Fatal without stem cell/bone marrow transplant in the chronic phase
double treatment with a type of targeted cancer drug called a tyrosine kinase inhibitor (TKI) - e.g. imatinib
features common to myeloproliferative neoplasms
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 vera (PV)?
High haemoglobin/haematocrit accompanied by erythrocytosis (a true increase in red cell mass) but can have excessive production of other lineages (white cells, platelets)
what is it important to distinguish polycythaemia vera from?
secondary polycythaemia (chronic hypoxia, smoking, erythropoietin-secreting tumour etc)
pseudopolycythaemia (eg dehydration, diuretic therapy, obesity)
what causes haematocrit to be raised in pseudopolycythaemia?
decrease in plasma volume
e.g. dehydration, diuretic therapy, obesity
polycythaemia vera clinical features
Clinical features common to MPN
Headache, fatigue (remember blood viscosity raised NOT plasma viscosity)
Itch (aquagenic puritis)
investigation of polycythaemia (clinical and lab)
History (eg history suggestive of a secondary polycythaemia?)
Examination (eg splenomegaly?)
FBC, film
JAK2 mutation status (IMPORTANT)
–
Investigation for secondary/pseudo causes (CXR, O2 saturation/arterial blood gases, drug history)
JAK2 analysis
what percentage of patients with polycythaemia vera have JAK2 mutation
95%
Polycythaemia vera treatment
- Vensect to haematocrit <0.45
- Aspirin
- Cytotoxic oral chemotherapy (eg Hydroxycarbamide)
what is Essential Thrombocythaemia (ET)
Uncontrolled production of abnormal platelets
Essential Thrombocythaemia.
platelet function abnormal - what can this cause?
- thrombosis
- at high levels can also cause bleeding due to acquired von Willebrand disease
Essential Thrombocythaemia clinical features
Clinical features common to MPN (particularly vasoocclusive complications)
Bleeding (unpredictable risk especially at surgery)
if suspecting essential thrombocythaemia, what is it important to exclude?
reactive thrombocytosis (Blood loss, inflammation, malignancy, iron deficiency)
also exclude CML
Essential Thrombocythaemia genetics and percentages of patients positive for these mutations
JAK2 mutations in approx. 50 - 60%
CALR (Calreticulin) in approx. 25%
MPL mutation in approx. 5%
10-20% of patients will be ‘Triple Negative’
