Myeloproliferative neoplasms MPN Flashcards
what are myeloproliferative neoplasms
clonal haemopoeitic stem cell disorder resulting in increased production of 1 or more type of haemopoeitic cells
how can myeloproliferative neoplasms MPN be classified
BCR-ABL1 positive
BCR-ABL1 negative
what kind of MPN is BCR-ABL1 positive
Chronic myeloid leukaemia CML
what kinds of MPN are BCR-ABL1 negative
polycythaemia vera PV
essential thrombocythaemia ET
myelofibrosis
what lab and clinical features suggest a MPN
high granulocyte count +- high red cell count +- high platelet count +- eosinophilia/basophilia splenomegaly thrombosis in an unusual place WITH NO REACTIVE EXPLANATION
what is chronic myeloid leukaemia
proliferation of abnormal granulocytes and their precursors (sometimes other cell lineages too)
how can CML progress
chronic phase –> accelerated phase –> blast crisis
list clinical features of CML
asymptomatic splenomegaly gout hypermetabolic priapism hyperleukocytosis
list laboratory features of CML
blood count:
normal/low Hb
leukocytosis with neutrophilia, myelocytes, eosinophilia, basophilia
thrombocytosis
what genetic abnormality is a hallmark of CML
philadelphia chromosome
what is the philadelphia chromosome
mutated chromosome 22
usually a translocation t(9;22)
what is the pathology as a result of the philadelphia chromosome in CML
results in new chimaeric gene: BCR-ABL1
the product of this is a tyrosine kinase which causes abnormal phosphorylation resulting in the features seen in CML
what treatment is used in CML
tyrosine kinase inhibitors
what are common clinical features of BCR-ABL1 negative MPN
asymptomatic increased cell turnover: gout, weight loss, fatigue, sweats splenomegaly marrow failure THROMBOSIS : arterial and venous erythromelalgia
what is polycythaemia vera PV
high Hb/Hct with erythrocytosis (making it a true increase in red cell mass) but can have increased production in other cell lineages
what are differential diagnoses for polycythaemia
Secondary polycythaemia (hypoxia induced): high altitude, COPD, OSA, smoking, EPO tumour Pseudopolycythaemia: dehydration, diuretics, alcohol, obesity
clinical features of PV
same as MPN plus
headache, blurred vision, fatigue
thrombosis
aquagenic pruritis
what is aquagenic pruritis and in which condition is it seen
itchy skin after a shower
seen in PV
investigations for PV
History and examination Rule out differentials FBC Blood film Genetics: JAK2 mutation
what is the implication of a JAK2 mutation in BCR-ABL1 negative MPN
JAK2 is a kinase
mutation causes loss of auto-inhibition resulting in increased erythropoeisis in the absence of a ligand
treatment of PV
venesection: Hct<0.45
aspirin
cytotoxic chemotherapy - hydroxycarbamide
what is essential thrombocythaemia ET
uncontrolled production of abnormal platelets
what are consequences of ET
thrombosis
bleeding (due to acquired vWD)
clinical features of ET
same as MPN
vaso-occlusive complications
bleeding
what must you rule out before diagnosing ET
reactive thrombocytosis
causes of reactive thrombocytosis
blood loss
infection/inflammation
malignancy (LEGO+C)
iron deficiency
iron deficiency can cause a thrombocytosis, true or false
true
investigations for ET
rule out CML
genetic testing: JAK2, CALR, MPL
bone marrow
treatment of ET
antiplatelets
cytotoxic redutive agents - hydroxycarbamide, IFNa
what are the subtypes of myelofibrosis
idiopathic
post polycythaemia/ET
features of myelofibrosis
marrow failure
bone marrow fibrosis
extramedullary haemoatopoeisis
what are the clinical features of myelofibrosis
same as MPN panyctopaenia - anaemia: SOB, fatigue, pallor - thrombocytopaenia: bleeding, petechiae - neutropaenia: infection, fever splenomegaly hypercatabolic
investigations and findings for myelofibrosis
FBC blood film dry aspirate fibrosis on trephine biopsy genetics: JAK2 > CALR > MPL > triple negative
treatment of myelofibrosis
supportive: transfusions, antibiotics
allogenic stem cell transplant
splenectomy
JAK2 inhibitors
what are the characteristic blood film features of myelofibrosis
leukoerythroblastic
tear drop shaped poikilocyte RBC
what are causes of leukoerythroblastic blood films
reactive eg sepsis
marrow infiltration
myelofibrosis
MPN is the most common cause of raised blood cell counts, true or false
FALSE
reactive causes of high blood counts are more common
