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’
Essential Thrombocythaemia treatment
Anti-platelet agents
- Aspirin
Cytoreductive therapy to control proliferation
- hydroxycarbamide, anagrelide, interferon
alpha
Myelofibrosis presentation (on testing)
Marrow failure (variable degrees)
Bone marrow fibrosis (no alternative cause)
Extramedullary hematopoiesis (liver and spleen)
Leukoerythroblastic film appearances
- IMPORTANT!!
Teardrop-shaped RBCs in peripheral blood
myelofibrosis clinical features
Clinical features common to MPD
Marrow failure
- anaemia, bleeding, infection
Splenomegaly
- LUQ abdominal pain
- Complications including portal
hypertension
Hypercatabolism
myelofibrosis lab diagnosis
typical blood film (tear-drop shaped RBC and leucoerythroblastic)
dry aspirate
fibrosis on trephine biopsy
JAK2, CALR, MPL mutations (majority JAK2 > CALR > MPL. Approx 10% ‘triple negative’)
why dry tap/aspirate in lab diagnosis of myelofibrosis
scar tissue
leucoerythroblastic film is characterised by…
characterized by the presence of immature forms of red and white cells in the peripheral blood
causes of leucoerythroblastic blood film
- reactive (sepsis)
- marrow infiltration
- myelofibrosis
myelofibrosis treatment
Supportive care (blood transfusion, platelets, antibiotics)
Allogeneic stem cell transplantation in a select few (if young and fit, high risk disease)
Splenectomy (CONTROVERSIAL, rarely performed)
JAK2 inhibitors (improve spleen size, constitutional symptoms, ?survival)
in high blood counts, which is more common, myeloproliferative neoplasms or reactive causes
reactive causes
causes of raised platelet count apart from myeloproliferative neoplasms
Infection
Iron deficiency
Malignancy
Blood loss
causes of raised granulocyte count apart from myeloproliferative neoplasms
Infection: eg pyogenic bacteria causing neutrophilia
Physiological eg post-surgery, steroids
causes of raised red cell count apart from myeloproliferative neoplasms
Dehydration (diuretics): pseudopolycythaemia
Secondary polycythaemia (eg hypoxia-induced)
