Myeloproliferative Disorders Flashcards
What cells are of the myeloid lineage?
granulocytes (eosinophils, neutrophils, basophils)
red blood cells
platelets
How do the myeloproliferative disorders differ from leukaemia?
maturation is preserved - they retain ability to differentiate into red blood cells, platelets and granulocytes
What are the disorder subtypes?
BCR-ABL1 positive
BCR-ABL1 negative
What are the BCR-ABL1 positive myeloproliferative disorders?
chronic myeloid leukaemia
What are the BCR-ABL1 negative myeloproliferative disorders?
polycythaemia rubra vera
essential thrombocythaemia
idiopathic myelofibrosis
What happens in chronic myeloid leukaemia?
overproduction of granulocytes
What happens in polycythaemia rubra vera?
overproduction of red blood cells
What happens in essential thrombocythaemia?
overproduction of platelets
When should you consider a myeloproliferative disorder?
no reactive explanation
increased granulocyte count +/-
increased red blood cells/Hb +/-
increased platelet
What is polycythaemia?
abnormally increased concentration of Hb in blood
What are the 2 classifications of polycythaemia?
absolute - increased RBC mass
relative/pseudo - decreased plasma volume, normal RBC mass e.g. dehydration
What are the causes of absolute polycythaemia?
primary: polycythaemia rubra vera (PRV)
secondary: hypoxia, inapprop. erythropoietin secretion e.g. renal carcinoma, hepatocellular carcinoma
What mutation is found in >90% of people it PRV?
mutation in JAK2
loss of auto inhibition - activation of erythropoiesis in absence of ligand
What should you distinguish PRV from when making your diagnosis?
secondary absolute polycythaemia
relative/psuedopolycythaemia
What is increased in PRV?
increased Hb/ haematocrit
can have increased granulocytes and platelets
What are the clinical features of PRV?
can be asymptomatic
hyper viscosity (headaches, dizziness, tinnitus, visual disturbance)
thrombosis (erythromelalgia, claudication, MI, TIA)
fatigue, itch, splenomegaly
gout (increased rate due to increased red cell turnover)
What is erythromelalgia?
burning sensation in fingers and toes
In PRV, what does increased proliferation of red blood cells, granulocytes and platelets cause?
hyper viscosity
thrombosis
What are the investigations for PRV??
JAK2 mutation
FBC (increased Hb, increased haemotocrit, increased PCV, also can have increased WCC, platelets)
exam - splenomegaly?
bone marrow - erythroid hyperplasia
What is the treatment of PRV?
venesection to keep haematocrit <0.45 (to prevent thrombosis)
cytotoxic chemo e.g. hydroxycarbamide
low dose aspirin
What is essential thrombocythaemia?
clonal proliferation of megakaryocytes
uncontrolled production of abnormal platelets
What does the high level of abnormal platelets cause in essential thrombocythaemia?
bleeding or arterial/venous thrombosis and microvascular occlusion
What are the clinical features of essential thrombocythaemia?
headache, atypical chest pain
thrombosis, erthyromelalgia
splenomegaly
light headed, fatigue, wt loss
How is essential thrombocythaemia diagnosed?
rule out other causes of thrombocytosis (increased platelets) e.g. infection, bleeding, malignancy, inflammation, trauma
exclude CML
bone marrow
What is the treatment of essential thrombocythaemia?
low dose aspirin
hydroxycarbimide to reduce proliferation (if older, previous thrombosis)
What is idiopathic myelofibrosis?
hyperplasia of megakaryocytes - produce platelet-derived growth factor –> marrow fibrosis (leading to marrow failure)
extra medullary haematopoeisis –> hepatosplenomegaly
What are the clinical features of idiopathic myelofibrosis?
marrow failure: anaemia, infection, bleeding
splenomegaly
thrombosis, headaches, gout
How is idiopathic myelofibrosis diagnosed?
trephine biopsy - fibrosis
blood film: tear drop shaped RBC, leukoerythroblastic cells
What is the treatment of idiopathic myelofibrosis?
marrow support (red cell transfusion, platelets, neutrophils) allogeneic stem cell transplant - can be curative in young, high risk of mortality
What is chronic myeloid leukaemia?
uncontrolled proliferation of myeloid cells
What are the clinical features of CML?
features common with myeloproliferative disorders e.g. splenomegaly (abdominal discomfort), gout
weight loss, fever, fatigue, sweats
bleeding
What is the Philadelphia chromosome?
present in CML
gene product - tyrosine kinase activity
results in new gene: BCR-ABL1
How is CML diagnosed?
FBC: increased WCC (eosinophils, basophils, neutrophils), HB decreased or normal, platelets variable
bone marrow: hyper cellular
What is the treatment of CML?
BCR ABL tyrosine kinase inhibitors e.g. imatinib
