Myeloproliferative Neoplasms (MPN) Flashcards
what is MPN?
disorder of clonal HSCs with increased production of one or more types of haemopoietic cells
maturation is relatively preserved
classification of MPN
- BCR-ABL1 negative
2. BCR-ABL1 positive
what is encompassed in BCR-ABL1 negative?
polycythaemia vera
essential thrombocythaemia
primary myelofibrosis
what is encompassed in BCR-ABL positive?
CML
what is CML?
chronic myeloid leukaemia= increased granulocytes due to philadelphia chromosome)
define chronic myeloid leukaemia?
proliferation of myeloid cells (granulocytes, monocytes, platelets and RBCs)
phases in CML
chronic phase
blast crisis
presentation of CML
splenomegaly
hypermetabolic symptoms= gout
hyperleukocytosis and priapism
diagnosis of CML
FBC
hypercellular bone marrow
philadelphia chromosome
what does the FBC in CML show?
leucocytosis with neutrophilia and myeloid precursors, eosinophilia, basophilia
what is the philadelphia chromosome?
chromosome 9 and chromosome 22 trade parts
what does the philadelphia chromosome cause in CML?
chromosome 22 now contains BCR-ABL1 gene which causes phosphorylation
how to distinguish reactive changes
only neutrophil count raised
plasma viscosity
CRP
management of CML
tyrosine kinase inhibitors e.g. imatinib
blast crisis is fatal so may need transplant
features common to BCR-ABL1 negative
>65 often asymptomatic increased cellular turnover splenomegaly marrow failure thrombosis
increased cell turnover
gout
fatigue
weight loss
sweats
what is polycythaemia vera (PV)?
erythrocytosis causing high Hb and Hct
what does PV need to be distinguished from?
- secondary polycythaemia
- pseudo-polycythaemia
causes of secondary polycythaemia
chronic hypoxia (COPD)
smoking
EPO-secreting tumour
causes of pseudo-polycythaemia
dehydration
diuretics
obesity (reduced plasma, normal red cell mass)
presentation of PV
features common to MPN
headache, fatigue, blood viscosity raised
itch (aquagenic pruritis- itchy after a hot bath)
diagnosis of PV
splenomegaly
JAK2 mutation
investigations for other causes
what is the JAK2 mutation?
mutated kinase with loss of auto-inhibition causing activation of erythropoiesis
investigations for other causes of polycythaemia
CXR
O2 saturation
DH
EPO levels
management of PV
mainly to stop thrombus formation:
- venesect to Hct <0.45
- aspirin
- cytotoxic oral chemotherapy e.g. hydroxycarbamide
what is essential thrombocythaemia?
uncontrolled production of abnormal platelets
what does essential thrombocythaemia cause?
thrombosis
acquired VWD
why does ET cause acquired VWD?
platelets absorb VWF
presentation of ET
vaso-occlusive complications e.g. black toe
bleeding
diagnosis of ET
FBC
genetics= JAK2, CALR, MPL, some are triple negative
management of ET
antiplatelets e.g. aspirin
cytoreductive therapy to control proliferation e.g. hydroxycarbamide, anagrelide, IFN-alpha
what is myelofibrosis?
bone marrow fibrosis and extramedullary haematopoiesis
presentation of MF
marrow failure (anaemia, infection, bleeding)
splenomegaly (LUQ pain, portal hypertension)
hypercatabolic
diagnosis of MF
blood film
dry aspirate or fibrosis on trephine biopsy
JAK2, CALR, MPL or triple negative
what does the blood film show in MF?
leucoerythroblastic + teardrop RBCs
other causes of leucoerythroblastic blood film
sepsis
marrow infiltration
management of MF
blood transfusion, platelet transfusions, antibiotics
allogenic stem cell transplant in some
splenectomy
JAK2 inhibitors
why are more measures taken in MF?
more aggressive
