Myeloproliferative disorders Flashcards
What are the myeloproliferative disorders?
clonal haemopoietic stem cell disorders
What is the difference ebtween MPD and acute leukaemia?
maturation is relatively preserved in MPD
How are the myeloproliferative disorders broadly categorized?
BCR-ABL1 negative or positive
What MPD is BCR-ABL positive?
chronic myeloid leukaemia
Which MPDs are BCR-ABL negative?
idiopathic myelofibrosis; essential thrombocythaemia; polycythaemia rubra vera
When should MPD be considered as a diagnosis?
when there are high counts without a reactive explanation, esp. a basophilia; thombosis in an unsual place; splenomegaly
What is sene in the chronic phase of CML?
excess of mature neutrophils and some precurosors
What is seen in the accelerated phase of CML?
proportion of mature cells compared to precurosors is dropping
what is seen in the blast crisis phase of CML?
looks like AML- monomorphic
What are the clinical features of CML?
splenomegaly; hypermetabolic symptoms; gout; increased viscosity problems- priapism etc.
What is seen on blood coutn with CML?
normal/decreased Hb; leucocytosis with neutrophilia and myelocytes; eosinophilia; basophilia; thombocytosis
What is the genetic abnormality in CML?
t(9:22)- Philidelphia chromsome
What is the result of the philidelphia chromosome?
a new gene: BCR-ABL1
What is the product of BCR-ABL1?
tyrosine kinase which causes abnormal phosphorylation (signalling)
What is the treatment for CML?
imatinib
What is polycythaemia rubra vera?
high Hb/hct accompanied by erythrocytosis (a true increase in red cell mass) but can have excessive production of otehr lineages
What are causes of secondary polycythaemia?
chronic hypoxia; smoking; EPO-secreting tumour
What are the causes of pseudopolycythaemia?
dehydration; diuretics; obesity
What are the clinical features of PRV?
headache; fatigue; aqaugenic pruritis (warm water)
What mutation is seen with PRV?
substitution in JAK2 resulting in loss of auto-inhibition
What is JAK2?
a kinase
What investigations should be done to look for secondary or pseudo causes of PRV?
CXR; O2 sats/ABGs; drug hx)
What drug is implicated in pseudopolycythaemia?
testosterone
What is the treatment for PRV?
venesect to hct <0.45; aspirin; cytotoxic oral chemo (hydroxycarbamide)
What is essential thrombocythaemia?
uncontrolled production of abnormal platelets
What are the results of abnormal platelet function?
increased thrombosis risk; hgih levels can also cause bleeding
Why do ET patietns have a bleeding risk with lots of platelets?
acquired von Willebrand disease
What are the causes of reactive thromobytosis?
blood loss; inflammation; malignancy; iron deficiency
What disease should be excluded before ET is diagnosed?
CML- in early stages can just be a thrombocytosis
What mutations are implicated in ET?
JAK2; CALR; MPL
What is seen characteristicall on marrow with ET?
clusters of megakaryocytes
What is the treatment for ET?
aspirin; cytoreductive therpay- hydroxycarbamide; anagrelide; IFN-alpha
What are the causes of myelofibrosis?
idiopathic; post-polycythaemia or ET
What is seen with idiopathyic myelofibrosis?
marrow failure; bone marrow fibrosis; extramedullary haemopoiesis; leukoerythroblastic film; tear-drop RBCs
What is seen on bone marrow aspirate in myelofibrosis?
dry aspirate
What mutations may be seen in myelofibrosis
?
JAK2; CALR
What are the causes of a leucoerythroblastic film?
reactive (sepsis); marrow infiltration; myelofibrosis
What drugs are used in MF?
JAK2 inhibitors work on all MF patients, even wtihout JAK2 mutation
