When Haemopoiesis Goes Wrong... In Other Ways Flashcards
What are myeloproliferative disorders?
- Now classified by WHO as Myeloproliferative neoplasms (MPN)
- Essential Thrombocythaemia
- Polycythaemia Vera
- Myelofibrosis
- Chronic Myeloid Leukaemia
All of these disorders involve dysregulation at the multipotent haematopoietic stem cell
What are the clinical features of myeloprolifertaive disorders?
- Overproduction of one or several blood elements with dominance of a transformed clone.
- Hypercellular marrow / marrow fibrosis - extra deposition of fibrosis in bone marrow
- Cytogenetic abnormalities.
- MOst have thrombotic and/or haemorrhagic diatheses.
- All have extramedullary haemopoiesis (liver/spleen).
- All have potential to transform to acute leukaemia.
- Overlapping clinical features.
What mutation is common in myeloprolifrative disorders?
Many patients have a specific point mutation in one copy of the Janus kinase 2 gene (JAK2)
- a cytoplasmic tyrosine kinase on chromosome 9, which causes increased proliferation and survival of haematopoietic precursors We now have specific drugs targeting the aberrant protein
What is polycythaemia Vera?
• Diagnostic criteria = High haematocrit (>0.52 in men, >0.48 in
women) OR raised red cell mass
• JAK2 V617F mutation is present in approximately 95% PRV patients
• No reactive cause found
• Some patients also have high platelets & neutrophils
• Median age 60 yrs
• Male=Female
What are the clinical features of PV?
Clinical features: • Significant cause of arterial thrombosis • Venous thrombosis • Haemorrhage into skin or GI tract • Pruritis • Splenic discomfort , splenomegaly • Gout • In some transformation to myelofibrosis or acute leukaemia Capillaries burst
How is PV managed?
- Venesection to maintain the Hct to <0.45 - remove blood
- Aspirin 75 mg unless contraindicated - to reduce risk of thrombosis
- Manage CVS risk factors
- Sometimes drugs to reduce the overproduction of cells should be considered
What needs to be considered if high Hb or haematocrit is noted?
Need to consider why
Is this polycythaemia vera or… Is there another explanation?
What else could cause an excess of red cells to be formed?
What is polycythaemia?
• Polycythaemia= an increase in circulating red cell
concentration typified by a persistently raised haematocrit (Hct).
This increase can be;
Relative = normal red cell mass with decreased plasma volume or
Absolute = increased red cell mass
- primary - polycythemia vera - abnormality originates in bone marrow
- Secondary –driven by erythropoietin EPO production - either a physiological response to hypoxia or abnormal production
Check if on diuretics - these can dehydrate
If it is absolute, need to work out if primary or secondary
What are the classes of secondary polycythemia?
Physiologically appropriate EOP production - in response to tissue hypoxia
Pathological EPO production
Other causes of EPO in blood
What are the causes or each of the classes of secondary polycythemia?
Central Hypoxia – Chronic lung disease R to L shunts Training at altitude CO poisoning - red cell mass increases
Renal Hypoxia – Renal artery stenosis Polycystic disease
Hepatocellular carcinoma Renal cell cancer Cerebellar haemangioblastoma Uterine tumours Phaeochromocytoma ..all produce ectopic EPO
Some people give thesmseves erythropoietin so that RBC mass increases so their athletic/cycling performance increases
What is essential thrombocythaemia?
Excess platelets - overproduction of megakaryocytes (large and excess) - leads to thrombotic events
What is the management of essential thrombocythaemia?
• Any cardiovascular risk factors should be aggressively managed
• Aspirin
• High risk patients:
• >60 years, platelet count >1500 or disease-related thrombosis/haemorrhage
• return the platelet count into the normal range with drug such as hydroxycarbomide
- difficult to selectively remove platelets
What should be done if a high platelet count is noted?
Ensure it is persistent rather than transient before investigating for ET
First look for and exclude reactive causes
• Infection
• Inflammation (Inflammatory bowel disease, Rh arthritis)
• Other tissue injury (e.g. surgery, trauma, burns)
• Haemorrhage
• Cancer
• Redistribution of platelets - Post-splenectomy and hyposplenism
What is myelofibrosis?
Heavily fibrotic marrow, little space for haemopoiesis
Blood film shows red cells looking like tear drops
• clonal haemopoietic stem cell proliferation
• May be end result of PV or ET, or
• Primary disease (PMF)
• PMF starts with proliferative phase when all counts may be
high
• Then in all cases progressive pancytopeniadue to bone
marrow fibrosis and hypersplenism
Describe the bone marrow liver and spleeen I myelofibrosis
Increasing stages of collagen and then fibrotic tissue - fewer areas of normal production of blood cells
clinically myelofibrosis quite rare
spleen grows liver starts to grow - they take over with extramedullary haematopoiesis - splenomegaly and hepatomegaly
