myeloproliferative disorders Flashcards
what is a myeloproliferative disease
monoclonal proliferation of myeloid precursors
how do myeoproliferative disorders differ from acute leukaemia
MPD still have ability to mature - lots of abnormal mature cells
acute leukaemia - proliferation of precursors that don’t mature - lots of blasts in peripheral blood
what are the 4 MPDs
polycythaemia rubra vera (red cells)
essential thrombocythaemia (platelets)
idiopathic myelofibrosis
chronic myeloid leukaemia (white cells)
what MPD is BCR-ABL1 positive and why
CML - Philadelphia chromosome produces BCR-ABL1 protein
what is Philadelphia chromosome
9:22 translocation
what is BCR-ABL1
tyrosine kinase
course of CML
chronic phase - few if any symptoms
accelerated phase - increasingly worse
blast transformation - acute leukaemia and death (acquired maturation defect)
presentation of CML
B symptoms - weight loss, night sweats, fever fatigue gout bleeding abdo pain
what are symptoms common to the MPDs
increased cell turnover - gout, fatigue, weight loss, sweats
splenomegaly - abdo pain, early satiety
marrow failure - fibrosis, other lineages affected
hyperviscosity - thrombosis
blood count in CML
increased WBC (neutrophils, eosinophils, basophils) low Hb (bone marrow failure) platelets variable high urate and B12
if high WCC, why is patient immunosuppressed
these white cells are abnormal
bone marrow aspirate in CML
hypercellular
what treatment can be given for CML
tyrosine kinase inhibitors (imatinib) if Philadelphia chromosome is present
fatal without bone marrow transplant in chronic stage
what are secondary causes of polycythaemia
chronic hypoxia (COPD, smoking, EPO tumour) dehydration, diuretics, obesity
what constitutes polycythaemia rubra vera (true polycythaemia)
high Hb/haematocrit with erythrocytosis (increase in red cell mass)
presentation of PRV
headache
aquagenic itch
plethoric appearance
what investigations should be done in suspected PRV
rule out secondary causes - screen for COPD, smoking, diuretics
FBC - high Hb, high haematocrit, may have increased WBC/platelets
bone marrow aspirate - hypercellular with erythroid hyperplasia
low serum EPO
normal PaO2
increased red cell mass on Cr15 labelling
what genetic mutation is often present in PRV and what does it cause
JAK2 - cells don’t require EPO
treatment of PCV
vensect to haematocrit <0.45 (young patients)
aspirin
cytotoxic oral chemotherapy (old patients) -hydroxycarbamine
what is essential thrombocythaemia
proliferation of megakaryocytes leading to increased abnormal function
platelets >1000
presentation of ET
vasoocclusive symptoms - thrombosis bleeding - platelets are not functioning (surgery) headache chest pain light headed
what are causes of reactive thrombocytosis
blood loss inflammation malignancy iron deficiency RULE THESE OUT
what genetic mutations might be present in ET
Jak2
CALR
MPL
bone marrow aspirate in ET
clusters of megakaryocytes
treatment for ET
aspirin
if >60 give hydroxycarbamide
what is myelofibrosis
hyperplasia of megakaryocytes which produce platelet
derived growth factor
leads to marrow fibrosis and myeloid metaplasia
when is it common to get myelofibrosis
post-PRV or ET
can be idiopathic
presentation of myelofibrosis
marrow failure and fibrosis (anaemia, low platelets, low WBC) extramedullary haematopoiesis (hepatosplenomegaly - early satiety, LUQ pain, portal hypertension)
diagnosis of MPD
blood film - tear-drop shaped RBC and leucoerythroblastic
fibrosis on bone marrow biopsy
JAK2 or CALR mutation
why do red cells appear tear-dropp shaped in myelofibrosis
trying to squeeze out of fibrosed marrow - deforms them
MF treatment
blood transfusions platelets antibiotics bone marrow transplant in young people splenectomy? JAK2 inhibitors
