Myeloproliferative Neoplasms Flashcards
myeloproliferative neoplasms (MPN) used to be called what?
myeloproliferative disorders
what does myeloproliferative mean?
proliferation of bone marrow/bone marrow lineages
myeloproliferative neoplasms are clonal haematopoietic stem cell disorders, what does this mean?
increased production of one or more types of haematopoietic cells
maturation is relatively preserved (in contract to acute leukaemia)
sub-types of myeloproliferative neoplasms?
BCR-ABL1 negative
BCR-ABL1 positive
types of BCR-ABL1 negative myeloproliferative neoplasms?
primary myelofibrosis polycthaemia vera (overproduction of RBCs) essential thrombocytopenia (overproduction of platelets)
types of BCR-ABL1 positive myeloproliferative disorders
chronic myeloid leukaemia (overproduction of granulocytes, Philadelphia chromosome)
when should a myeloproliferative neoplasm be considered as a diagnosis?
high granulocyte count \+/- high RBCs/Hb \+/- high platelets \+/- eosinophilia/basophila splenomegaly thrombosis in unusual place (must have no reactive explanation)
what happens in CML?
proliferation of myeloid lineage cells (granulocytes and their precursors, other lineages including platelets)
previously, had a chronic phase with intact maturation of cells for 3-5 years followed by “blast crisis” reminiscent of acute leukaemia with maturation defect
CML is fatal in the chronic phase without what?
stem cell/bone marrow transplant
3 phases of CML?
chronic phase
accelerated phase
blast crisis
clinical features of CML?
asymptomatic splenomegaly hypermetabolic symptoms gout miscellaneous (problems related to hyperleukocytosis problems, priapism)
lab features of CML?
blood count changes
- normal/reduced Hb, leucocytosis with neutrophilia and myeloid precursors, eosinophilia, basophilia, thrombocytosis
what is the hallmark of CML?
Philadelphia chromosome
genetics of CML?
Philadelphia chromosome results in a new chimaeric gene (BCR-ABL1)
the gene produces a tyrosine kinase which causes abnormal phosphorylation (signalling) leading to haematological changes in CML
types of BCR-ABL1 negative myeloproliferative neoplasms
polycthaemia vera (PV) essential thrombocytopenia (ET) primary myelofibrosis (PMF) others
features common to myeloproliferative neoplasms?
asymptomatic increased cell turnover (gout, fatigue, weight loss, sweats) signs of splenomegaly marrow failure thrombosis (arterial and venous)
what is PV?
polycthaemia vera
high Hb/haematocrit accompanied by erythrocytosis (true increase in RBC mass) but can have excessive production of other lineages
how can PV be distinguished from secondary polycthaemia?
secondary associated with chronic hypoxia, smoking and erythropoietin secreting tumour etc
how can PV be distinguished from pseudopolycthaemia?
pseudopolycthaemia associated with dehydration, diuretic therapy, obesity etc
true vs pseudo polycthaemia?
true = actual increase in number of RBCs pseudo = same amount of RBCs but RBCs are dissolved in less plasma so looks like relatively more RBCs
clinical features of PV?
same features common to all MPNs
headache
fatigue (result of increased BLOOD viscosity not plasma)
itch (aguagenic pruritis)
how is polycthaemia investigated?
history
examination (splenomegaly etc)
FBC
blood film
JAK2 mutation status (IMPORTANT)
investigate for secondary/pseudo causes (CXR, SpO2, ABGs)
other tests (erythropoietin, bone marrow biopsy done rarely)
what is JAK2 mutation?
JAK2 = a kinase
JAK2 mutation results in loss of auto-inhibition and activation of erythropoiesis present
present in 95% of PV cases, therefore part of screening for PV
how is PV managed?
venesect until haematocrit <0.45
aspirin
cytotoxic oral chemotherapy (hydroxycarbamide)
what is ET?
essential thrombocytopenia
uncontrolled production of abnormal platelets resulting in thrombosis and bleeding at high levels due to von Willebrand disease
clinical features of ET?
features common to all MPNs (particularly vaso-occlusive complications)
bleeding
how is ET diagnosed?
exclude reactive thrombocytosis (IMPORTANT)
exclude CML
check for genetic mutations (JAK2, CALR, MPL, some can be triple negative)
characteristic bone marrow appearance
how is ET managed?
anti-platelets (aspirin)
cytoreductive therapy to control proliferation (hydroxycarbamide, anagrelide, interferon alpha)
what can cause myelofibrosis?
idiopathic
post-polycthaemia
essential thrombocytopenia
features of idiopathic myelofibrosis?
marrow failure
bone marrow fibrosis with no alternative cause
extramedullary haematopoiesis (in liver and spleen)
blood film appearance of idiopathic myelofibrosis (important)
leucoerythroblastic film appearance
teardrop-shaped RBCs in peripheral blood
clinical features of myelofibrosis?
marrow failure (anaemia, bleeding, infection)
spelomegaly (LUQ pain, complications including portal hypertension)
hypercatabolism
also the clinical features common to all MPNs
lab diagnosis of myelofibrosis?
typical blood film (teardrop RBCs - “poikilocytes” and leucoerythroblastic)
dry aspirate
fibrosis on trephine biopsy (bone section)
JAK2, CALR, MPL mutations
causes of leucoerythroblastic film?
sepsis (reactive bone marrow)
marrow infiltration
myelofibrosis
what is leucoerythroblastic film?
presence of immature RBCs and WBCs
how is myelofibrosis managed?
supportive care (blood transfusions, antibiotics)
allogenic stem cell transplant in some
splenectomy (controversial)
JAK2 inhibitors
most common cause of high cell counts?
most commonly reactive
reactive causes of high granulocytes?
infection
physiological (post surgery, steroids etc)
reactive causes of high platelets?
infection
iron deficiency
malignancy
blood loss
reactive causes of high RBCs?
dehydration (diuretics) i.e - pseudopolycthaemia
secondary polycthaemia
