Chronic Myeloproliferative Disoders Flashcards
myeloproliferative disorders tend to produce cells that are mature/immature
MATURE
a disease of too many cells
a hypercellular marrow will not contain mature cells T or F
F, can have mature cells eg in MPD
pathophysiology of MPD
too many mature myeloid cells
BCR-ABL1 positive disorder…
CML
name the BCR-ABL1 negative MPDs
idiopathic myelofibrosis
essential thrombocythaemia
polycythaemia rubra vera
which leukaemia is associated with the philiadelphia chromosome
CML
describe the blood count in MPD
high cell counts eg granulocytes, red cells, platelets
1st thing to do if you get an abnormal blood count
repeat
non-cancer causes of high Hb
chronic hypoxia eg in COPD/sleep apnoea
upper age limit of normal for a stem cell transplant
60-65
name the 3 phases of CML
chronic phase
accelerated phase
blast crisis (appears like acute leukaemia)
clinical features of CML
asymptomatic splenomegaly hypermetabolic problems gout small vessel problems
why can you get gout in CML
high cell turnover causes inc breakdown deposits which cause gout
describe the blood count in CML
high WCC esp baso/eosinophils
normal-low Hb
what can be the earliest sign on a blood count of CML?
high platelets (thrombocytosis)
name the chromosomal translocation in philadelphia chromosome mutation in CML
t(9:22)
name the gene formed by the philadelphia chromosome
BCR-ABL1
name the gene product in CML and what it does
tyrosine kinase
abnormal phosphorylation
how many mutations are there in CML?
just 1 which is why its great for targeted therapy
MPD tends to be symptomatic T or F
F, asymptomatic
erythromyalgia is a cutaneous sign of what?
thrombocytosis
symptoms of inc cell turnover
gout
fatigue
weight loss
sweats
symptoms of MPD
asymptomatic mostly gout, fatigue, w loss, sweats splenomegaly marrow failure symptoms thrombosis eg MI/erythromyalgia
define PRV
high Hb/haematocrit accompanied by erythrocytosis
difference between PRV and secondary polycythaemia
in secondary polycythaemia it is usually caused by chronic hypoxia, smoking, EPO secreting tumour
difference between PRV and pseudopolycythaemia
in pseudopolycythaemia you are dehydrated, on diuretics or are obese
what is the problem in pseudopolycythaemia
reduced plasma vol means haematocrit is raised when red cell count is normal
clinical features of PRV
ITCH esp in water
MPD-like symptoms eg w loss, sweats, splenomegaly, marrow failure
headache
fatigue
pathophysiology of PRV
mutation in JAK2 gene causing loss of autoinhibition (activates erythropoeisis)
Ix PRV
FBC
film
mutational analysis for JAK2 mutation
CXR, ABG, O2 sats for secondary causes
what kind of substance is JAK2
a kinase
how sensitive is JAK2 to PRV
v specific (95%)
Tx PRV
venesect to get haematocrit to <0.45
aspirin
cytotoxic oral chemo via hydroxycarbamide
lifestyle changes for thrombotic risk
how does the morphology of platelets differ from normal in ET?
much bigger than usual
define essential thrombocythaemia
uncontrolled production of abnormal platelets
symptoms of ET
thrombosis
bleeding (can bind VWF and remove it from plasma)
MPD like symptoms
Ix ET
exclude reactive thrombocytosis and CML
mutation analysis
bone marrow biopsy only if mutational analyses are negative
causes of reactive thrombocytosis
blood loss
inflammation
malignancy
iron deficiency
appearance of ET on blood film
clustering of megakaryocytes
big megakaryocytes
what mutations can be present in ET
JAK2
calreticulin (CALR)
MPL
Tx ET
antiplatelet eg aspirin
cytoreductive therapy eg hydroxycarbamide
causes of myelofibrosis
idiopathic
progressed from PRV or ET
teardrop shaped RBCs in peripheral blood…
idiopathic myelofibrosis
describe the blood film of idiopathic myelofibrosis
leukoerythroblastic (this is important!)
clinical features of MF
marrow failure
splenomegaly
hypercatabolism
MPD like features
what happens in myelofibrosis
marrow failure and fibrosis
haematopoeisis is in liver and spleen as marrow is too damaged
Ix MF
blood film
trephine marrow biopsy
mutational analysis
causes of a leukoerythroblastic film
reactive eg sepsis/burns
marrow infiltration eg malignancy spread to bone marrow
myelofibrosis
what has to be present for a blood film to be leukoerythroblastic
nucleated red cells (erythroblasts)
myelocytes
Tx MF
supportive eg transfusion, antibiotics
allogeneic stem cell transplant if fit
JAK2 inhibitors
which BCR-ABL1 MPD has the worst prognosis?
MF
reactive causes of high granulocytes
infection
physiological eg surgery or steroids
reactive causes of high platelets
infetion
iron deficiency
malignancy
blood loss
reactive causes of high red cells
dehydration eg diuretics/low intake
hypoxia induced eg COPD/sleep apnoea
what do reactive lymphocytes look like on blood film
blue cytoplasm
big nucleus
