Myeloprolifertive Disorders Flashcards
What is the most common gene mutation in myeloproliferative disease?
JAK-2
What is polycythaemia?
Increased in red cell count and PCV
What is polycythaemia rubra vera?
Over-production of red cells
Increase in Hb and Hct
May have excessive production of other cells
What is JAK2?
Tyrosine kinase
How does polycythaemia rubra vera present?
Tiredness Itching Vertigo Headache Visual problems
Which group tend to present with polycythaemia rubra vera?
> 60
What may be common when a patient with polycythaemia rubra vera is hot?
Itching
What are the major complications of PRV?
Haemorrhage
Thrombosis
What may be found on examination of polycythaemia rubra vera?
Cyanosis
Splenomegaly
Hepatomegaly
What is found on FBC in PRV?
High Hb
What does bone marrow aspirate show in PRV?
Hypercellular
How is PRV managed?
Venesection to get Hct <0.45
Low dose aspirin
Cytotoxic oral chemotherapy
What is essential thrombocythaemia?
Overproduction of abnormal platelets
How does essential thrombocythaemia present?
Usually with thrombosis
Erythromelalgia
What is erythromelalagia?
severe burning pain, erythema and warmth at the extremities
How is essential thrombocythaemia diagnosed?
Persistently high platelet count with no identifiable cause
What may cause secondary polycythaemia?
Chronic hypoxia
Smoking
EPO-secreting tumour
What may cause pseudopolycythaemia?
Dehydration
Diuretic therapy
obesity
What is a psuedopolycythaemia?
When the plasma volume is reduction so the ratio seems high but the number of platelets is normal
What does the JAK2 mutation cause in PRV?
loss of auto-inhibitions and activation of erythropoiesis in the absence of a ligand
What cytotoxic chemo drug is given to treat PRV?
Hydroxycarbamide
Why does essential thrombocythaemia present with bleeding sometimes?
Causes acquired vWF disease
In which scenarios may a reactive thrombosis occur?
Blood loss
Inflammation
Malignancy
Iron def
Which mutations may be present in essential thrombocythaemia?
JAK2
CALR
MPL
What diagnosis should be excluded on suspicion of essential thrombocythaemia?
CML
How is ET managed?
Anti-platelets
Anagrelide
Hydroxycarbamide
Interferon alpha
What is the action of anagrelide?
Inhibits megakaryocyte differention
What is myelofibrosis?
Clonal proliferation of stem cells and abnormal myeloid cells
What causes the fibrosis in myelofibrosis?
Hyperplasia of abnormal megakaryocytes which release fibroblast stimulating factors
Give an example of a fibroblast stimulation factor
Platelet-derived growth factor
“Tear drop” red cells are seen in which conditions?
Idiopathic myelofibrosis
How does myelofibrosis present?
Marrow failure - anaemia, bleeding, infection
Splenomegaly
Extramedullary haemopoeisis
Which mutations are seen in myelofibrosis?
JAK2
CALR
How is idiopathic myelofibrosis treated?
Transfusions
Abx
Allogenic stem cell transplant
JAK2 inhibitors
Give an example of a JAK2 inhibitor
Ruxolitinib
What is the most common cause of raised cell counts?
Reactive
What characterises CML?
Uncontrolled growth of myeloid cells
Why is there less growth of non-myeloid cells in CML?
Overgrowth of myeloid cells push out the other cells and stop them growing
Which gene is abnormal in CML?
BCR-ABL1
Which chromosomal mutation is present in CML?
t(9;22)
Philadelphia chromosome
Where is the abnormal ABL gene in CML?
Chromosome 9
What is the effect of BCR-ABL mutations on DNA repair?
Inhibitory
Why may upper abdo pain be present in CML?
Hepatosplenomegaly
Why may CML cause poor appetite?
Spleen compresses stomach
What does FBC show in CML?
Leucocytosis
Increased white cells
Normocytic/normochromic anaemia
Why is gout more common in CML?
Increased cell turnover causes excess of purines
Why does CML cause dyspnoea and fatigue?
Anaemia
What causes the neurological defects in CML?
Hyperviscosity of the blood
What are the three main stages of CML?
Chronic
Accelerated
Blast crisis
Describe the chronic phase of CML
Asymptomatic
Mild fatigue or fullness
Describe the accelerated phase of CML
Sign that disease is progressing and blast crisis is imminent
What are the criteria for accelerated CML phase
Platelet counts <100,000 or >1,000,000
Increasing splenomegaly
10-19% myeloblasts
>20% basophils
Describe the blast crisis phase of CML
Final phase which behaves like an acute leukaemia
What are the criteria for blast crisis CML?
> 20% myeloblasts or lymphoblasts in blood or marrow
Large clusters of blasts in bone marrow
Chloroma
What is a chloroma?
Extramedullary solid collection of leukaemia cells
What does biochemistry show in CML?
Raised lactate dehydrogenase
Raised urate
What does blood film show in CML?
Granulocytes at all stages of development
How is CML managed?
Tyrosine kinase inhibitors
Bone marrow transplant
Give an example of a tyrosine kinase inhibitor?
Imatinib
How is response to imatinib treatment monitored?
PCR of BCAR-ABL
When would a bone marrow transplant be offered in CML?
No response to medical treatment
Young, healthy patient
Offers cure
