Myeloproliferative disorders Flashcards
what are the 2 main subtypes of myeloproliferative disorders
BCR-ABL1 positive and BCR-ABL1 negative
what diseases make up BCR-ABL1 negative
Idiopathic myelofibrosis
polycythaemia rubra vera
essential thrombocythaemia
what diseases make up BCR-ABL1 positive
Chronic Myeloid Leukaemia
what is chronic myeloid leukaemia
proliferation of myeloid cells
mostly granulocytes and their precursors
can be other lineages eg platelets
what is a devastating effect of CML
blast crisis which is reminiscent of acute leukaemia
fatal without stem cell/bone marrow transplantation in chronic phase
what are the stages of chronic myeloid leukaemia
chronic phase
accelerated phase
blast crisis
what are the clinical features of CML
asymptomatic, splenomegaly, hypermetabolic symptoms, gout, problems related to hyperleucocytosis problems, priaprism
blood count changes in CML
normal/decreased Hb
leucocytosis with neutrophilia and myeloid precursors (myelocytes), eosinophilia, basophilia
thrombocytosis
what is the hallmark of CML
philidelphia chromosome
what does the Philadelphia chromosome result in
a new (chimaeric) gene-BCR-ABL1
what does BCR-ABL1 produce
tyrosine kinase which causes abnormal phosphorylation leading to haematological changes in CML
what treatment can you give to BCR-ABL1 CML
imatinib-tyrosine kinase inhibitors
what are the features common to MPD
asymptomatic
increased cellular turnover-gout, fatigue, weight loss, sweats
symptoms/signs due to splenomegaly
marrow failure
thrombosis-arterial or venous including TIA, MI, abdominal vessel thrombosis, claudication, erythromelalgia
what do you need to distinguish PRV from
secondary polycythaemia and pseudopolycythaemia
what is PRV
high haemoglobin/haematocrit accompanied by erythrocytosis (a true increased in red cell mass but can have excessive production of other lineages
what can cause pseudopolycythaemia
dehydration, diuretic therapy, obsesity
clinical features of PRV
clinical features common to MPD
headache, fatigue
itch
investigation of polycythamia
history
examination eg splenomegaly
FBC, film
JAK2 mutation status
what is JAK2
a kinase
JAK2 mutations present in over 95% of what patients
PRV
what does JAK2 do
activates erythropoiesis in the absence of ligand
treatment of PRV
venesect to haematocrit<0.45
aspirin
cytotoxic oral chemotherapy eg hydroxycarbamide
what is ET
uncontrolled production of ABNORMAL platelelts
what does the abnormal platelet function in ET cause
thrombosis
at high levels can also cuase bleeding due to acquired von Willebrand disease
clinical features of ET
same as MPD
bleeding
what do you need to exclude with ET
reactive thrombocytosis
CML
what are the genetics in ET
JAK2 mutations in 50%CALR in those without mutant JAK2
MPL mutation
treatment for ET
aspirin
cytoreductive therapy to control proliferation eg hydroxycarbamide, anagrelide, interferon alpha
what are the causes of myelofibrosis
idiopathic or agnogenic myeloid metaplasia
post-polycythaemia or essential thrombocythaemia
what does idiopathic myelofibrosis look like on blood film
leukoerythroblastic film appearance
what shape are RBC in idiopathic myelofibrosis
tear-drop shaped
what are the potential causes of leucoerythroblastic film
reactive-sepsis
marrow infiltration
myelofibrosis
what is the treatment for MF
supportive care
allogenic stem cell transplantation
splenectomy
JAK2 inhibitors (improve spleen size, Qol, survival)
