Haematology - Myeloproliferative disorders Flashcards
what do myeloproliferative disorders arise from?
common myeloid progenitor cell
what controls haempopoiesis?
- growth factors (e.g. EPO)
- receptors
how do these receptors help control haemopoiesis?
- receptors interact with growth factors
- results in activation of kinases
- phosphorylation of intracellular molecules
- tyrosine kinases play important role
what are the kinases involved in myeloproliferative neoplasms?
- BCR-ABL (feature of CML)
- Janus kinases
explain how JAK kinases are involved
- GF bind to receptors
- activation of JAK
- leads to activation of STAT pathway
- JAK2 mainly in myeloid cells
- STAT transcription factor will move to nucleus
- get transcription of genes associated with cell growth and proliferation
- mutation that activates JAK = pathway not relying on cytokines binding to receptor
what are non BCR-ABL negative chronic myeloproliferative disorders characterized by?
- overproduction of mature myeloid cellular elements in blood
- increased fibrosis in bone marrow
- accomanied by various degrees of non-clonal reactive fibrosis in BM
- get spontaneous colony growth WITHOUT added EPO
what are the clinical presentations of these disorders?
- thrombosis (arterial)
- splenomegaly
- haemorrhage
list of chronic myeloproliferative disorders
- polycythaemia vera
- essential thrombocythaemia
- idiopathic myelofibrosis
- idiopathic erythrocytosis
- chronic granulocytic leukaemia
myeloproliferation vs myelodysplastic syndrome
myeloproliferation: proliferation and full differentiation (fully functional)
myelodysplastic syndrome: ineffective proliferation and differentiation
what is polycythaemia vera?
- inc production of RBCs
- independent of mechanisms that normally regulate haemopoesis
- compensatory inc in plasma volume
clinical presentation of of PV
- symptoms of hyperviscosity: headaches, light-headedness, stroke, visual disturbance
- increased histamine release (itch, peptic ulceration)
- variable splenomegaly
- plethora
- erythromelagia (red painful extremities)
- thrombosis
- retinal vein engorgement
- gout (inc red cell turnover)
investigations of PV
- high Hct
- high MCV
- high plasma volume
- high plt
- no circulating immature cells
what is pseudopolycythaemia?
- reduced plasma volume in presence of normal amount of Hb
principles of treatment for PV
- venesection
- cytoreductive therapy for maintenamce
- aim to reduce risks of thrombosis (aspirin, maintain plt levels)
what is idiopathic erythrocytosis?
- isolated erythrocytosis
- low EPO
- less likely to transform into MF or AML
- treated with venesection only
clinical presentation of essential thrombocythaemia
- incidental finding
- thrombosis
- bleeding (mucous membranes, cutaneous)
- minor: headaches, dizziness, visual disturbance
treatment of essential thrombocythaemia
- aspirin
- anagrelode (inhibits platelet formation but can accelerate myelofibrosis)
- HYDROXYCARBAMIDE (antimetabolite)
what is chronic idiopathic myelofibrosis?
- clonal myeloproliferative disease
- proliferation of megakaryocytes and granulocytic cells
- ass/ w/ reactive bone marrow fibrosis and extramedullary haemopoiesis
clinical presentation of chronic idiopathic myelofibrosis
- cytopaenias
- thrombocytosis
- splenomegaly
- hepatomegaly
- hypermetabolic state (weight loss, fatigure, night sweats, hyperuricaemia)
stages of myelofibrosis
pre-fibrotic
fibrotic
pre-fibrotic stage
- blood changes mild
- hypercellular marrow
fibrotic stage
- splenomegaly
- blood changes
- dry tap
- prominent collagen fibrosis
- later osteosclerosis
blood film of chronic idiopathic myelofibrosis
- leucoerythroblastic picture
- tear drop poikilocytes
- giant platelets
- circulating megakaryocytes
treatment of chronic idiopathic myelofibrosis
- transfusions
- hydroxycarbamide
- thalidomide
- bone marrow transplant
bad prognostic signs of chronic idiopathic myelofibrosis
- severe anaemia
- thrombocytopaenia
- massive splenomegaly
