Chronic Myeloproliferative Disorders Flashcards
What is the basic pathology of myeloproliferative disorders?
Proliferation of myeloid cells in the bone marrow
What bone marrow lineages come under ‘myelo’?
Erythrocytes, granulocytes and platelets
What are the BCR-ABL1 negative myeloproliferative disorders?
Polycythaemia rubra vera, essential thrombocythaemia, idiopathic myelofibrosis
What is the BCR-ABL1 positive myeloproliferative disorders?
Chronic myeloid leukaemia
What are some factors which would make you consider a diagnosis of MPD?
High granulocyte/platelet/erythrocyte counts, eosinophilia/basophilia, splenomegaly, thromboses in unusual places
What must there not be to diagnose a myeloproliferative disorder?
A reactive cause
What is a common ‘presenting feature’ of all myeloproliferative disorders?
Asymptomatic
What are some features due to increased cell turnover that can be seen in all myeloproliferative disorders?
Gout, fatigue, weight loss, sweats
Aside from the features of increased cell turnover, what are some other features which are common to all the myeloproliferative disorders?
Marrow failure, thrombosis, splenomegaly
Marrow failure is more likely to be a presentation of which myeloproliferative disorders?
Myelofibrosis or leukaemic transformation
What happens in polycythaemia rubra vera?
A high haematocrit/Hb accompanied by erythrocytosis (a true increase in red cell mass)
It is important to distinguish polycythaemia rubra vera from what other conditions?
Secondary polycythaemia or pseudopolycythaemia
What are some causes of secondary polycythaemia?
Chronic hypoxia, smoking (COPD), Epo secreting tumour, exogenous testosterone
What are some causes of pseudopolycythaemia?
Dehydration, diuretic therapy, obesity
Other than the features which are common to all myeloproliferative disorders, what are some features of PRV?
Headache, fatigue, itch, red appearance
When does the itch caused by PRV get worse?
On exposure to warm water
Aside from the usual investigations, what is the most important investigation to do for PRV?
JAK2 mutation status
What does the JAK2 mutation cause in terms of PRV?
Loss of auto-inhibition and activation of Epo
What are some investigations that can be used to determine if there is a secondary polycythaemia?
CXR, O2 sats/ABG, drug history
What are some infrequent tests that can be used in suspected PRV if JAK2 mutation is negative?
Epo levels and bone marrow biopsy
What is the treatment for PRV?
Venesect until haematocrit is < 0.45
Aside from venesection, what are some other treatment options for PRV?
Aspirin, smoking cessation, hydroxycarbamide
What is essential thrombocythaemia?
Proliferation of abnormally large platelets
The abnormal platelets in thrombocythaemia can initially cause thrombosis. After some time they can actually result in bleeding - why?
It causes acquired Von Willebrand’s disease by removing it from the plasma
The majority of cases of essential thrombocythaemia are picked up randomly, or with what presentation?
Digital ischaemia
What are some causes of reactive thrombocytosis which should be excluded before making a diagnosis of essential thrombocythaemia?
Blood loss, inflammation, malignancy, iron deficiency
What are some mutations which can be seen in people with essential thrombocythaemia?
JAK2, CALR, MPL
Essential thrombocythaemia has a characteristic bone marrow appearance, what is this?
Clustering of megakaryocytes
What are the treatment options for essential thrombocythaemia?
Aspirin, potentially cytoreductive therapy e.g. hydroxycarbamide
What is myelofibrosis?
Progressive fibrosis in the bone marrow
What are the main causes of myelofibrosis?
Idiopathic, or post polycythaemia or thrombocythaemia
What are some typical features of a blood film of idiopathic myelofibrosis?
Tear drop shaped RBCs and leucoerythroblastic
What are some mutations that can be seen in people with idiopathic myelofibrosis?
JAK2 or CALR
What are some supportive treatment options for idiopathic myelofibrosis?
Blood transfusions, platelets and antibiotics
What type of stem cell transplant can sometimes be used as a treatment for idiopathic myelofibrosis?
Allogenic
Ruxolitib is a drug which can be used to treat idiopathic myelofibrosis, what is its action?
JAK2 inhibition
