MEH 10 - Haemopoiesis Gone Wrong

Question 1

What conditions cause an overproduction (4 conditions)/underproduction (2 conditions) of cells in the bone marrow?

Answer 1

Overproduction = myeloproliferative neoplasms (MPN’s) - polycythaemia vera, essential thrombocytopenia, myelofibrosis + chronic myeloid leukemia.

Underproduction = asplastic anaemia or thrombocytopenia

Question 2

Give some examples of myeloproliferative neoplasms (MPN’s). What do these disorders all involve?
What are the clinical features of MPN’s?

Answer 2

• Essential thrombocytopenia/Polycythaemia Vera/Myelofibrosis. All involve dysregulation at the multipotent haemopoietic stem cell stage.
• Overproduction of 1 or several blood cells with dominance of the transformed clone.
• Tendency to clot or bleed
• Extramedullary haemopoiesis
• Potential to transform into acute leukemia

Question 3

What is Polycythaemia Vera (PV)?
What is the diagnostic criteria?
What are the clinical features?

Answer 3

• An MPN that results in the overproduction of RBC’s in the bone marrow. Usually caused by JAK2 mutation.
• A high haematocrit (>0.52 men, >0,48 in women, normal = 0.45). Some may have high neutrophils + platelets.
• Significant cause of arterial thrombosis. Can cause venous thrombosis, pruritis, splenomegaly and gout.

Question 4

What are the treatment strategies for PV?

Answer 4

• Venesection (removal of blood) to maintain HCT >0.45
• Aspirin to reduce risk of thrombosis
• Management of CVS risk factors
• Sometimes use drugs to reduce overproduction of cells

Question 5

Polycythaemia can be relative or absolute - what does each of these mean?
Absolute polycythaemia can be primary or secondary - what is the cause of each of these?

Answer 5

• Relative = normal red cell mass but decreased plasma volume (therefore just appears raised, diagnosis not made)
• Absolute = A genuine increase in RBC mass
• Primary = Polycythaemia Vera
• Secondary = Driven by EPO production, which can be appropriate (e.g.: response to tissue hypoxia) or inappropriate (e.g.: HCC, renal cell cancer, phaechromocytoma etc).

Question 6

Give a summary of how to figure out what is causing polycythaemia.

Answer 6

1) Is it relative or absolute - if relative don’t make diagnosis
2) If absolute, is is primary or secondary? If primary it is PV.
3) If secondary, find out whether increased EPO is appropriate or pathological + treat underlying cause.

Question 7

What is essential thrombocytopenia?
What are the management strategies for thrombocytopenia?
What should be ruled out before investigating for ET?

Answer 7

• An excess of platelets in the blood. Also see large + increased number of megakaryocytes in bone marrow.
• Manage CVS risk factors, give aspirin to prevent clots. Return platelet count to normal w/drugs such as hydroxycarbomide.
• Should rule out reactive causes, e.g.: infection, inflammation (RA, IBS), cancer etc, that would cause an increase in thrombocytes.

Question 8

What is myelofibrosis and what does it cause?

What are the clinical features of myelofibrosis?

Answer 8

• Another MPN where healthy marrow is replaced by fibrotic (scar) tissue, resulting in underproduction of blood cells.
• Significant cause of splenomegaly (+ maybe hepatomegaly) due to extramedullary haemopoiesis.
• Clonal haemopoietic stem cell proliferation
• End result of PV or ET
• Progression to PANCYTOPENIA due to bone marrow fibrosis + hypersplenism.
• Fatigue, sweats, pain and early satiety due to splenomegaly, transformation to leukaemia and early death.

Question 9

What is chronic myeloid leukemia? (CML)

What is imatinib now used to treat it?

Answer 9

• Another MPN where patients present with very high WCC, splenomegaly and hyperviscosity (sticky blood).
• In CML, BCR-abl fusion switches on tyrosine kinase receptor driving proliferation. Imatinib is an inhibitor of the receptor to prevent proliferation of leukemic cells.

Question 10

What is pancytopenia?

What are the causes of pancytopenia?

Answer 10

• A progression of MPN where there is a reduction in white cells, red cells + platelets.

1) Increased removal of cells - due to immune destruction (rare) or splenic pooling of cells (in splenomegaly).
OR
2) Reduced production of cells - due to B12/folate deficiency, blood cancers, marrow fibrosis, drugs or idiopathic aplastic anaemia.

Question 11

What is Aplastic anaemia?

Answer 11

• Pancytopenia with a hypocellular (empty) bone marrow in the absence of abnormal infiltrate and no fibrosis. Mortality is high as cure is very difficult.

Question 12

What is thrombocytopenia?

How is it caused?

Answer 12

• Thrombocytopenia is an abnormally low level of platelets in the blood.
• Can be inherited (rare) or acquired.
• Acquired due to decreased platelet production (e.g.: B12/folate deficiency), increased platelet consumption (e.g.: massive haemorrhage) or increased platelet destruction (e.g.: hypersplenism + splenic pooling of platelets).

Question 13

What are the consequences of severe thrombocytopenia?

Answer 13

• Easy bruising
• Petchiae (red/purple spots on skin) + purpura (same but non-blancing)
• Mucosal bleeding
• Severe bleeding after trauma (very poor clotting)