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MEH > Session 5: When Haemopoiesis Goes Wrong... In Other Ways > Flashcards

Session 5: When Haemopoiesis Goes Wrong... In Other Ways Flashcards

1
Q

What are myeloproliferative neoplasms?

A

A group of diseases of the bone marrow where there is an excess of cells produced.

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2
Q

How do MPNs occur?

A

Due to genetic mutations in the precursors of the myeloid lineage.

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3
Q

There are four major types of MPNs. They depend on which type of cell that is overproduced. Name them and give the overproduced cell/excess cell.

A

Polycythaemia (RBCs)

Essential thrombocythaemia (Megakaryocytes -> platelets)

Primary myelofibrosis (haematopoietic stem cells)

Chronic myeloid leukaemia (granulocytes)

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4
Q

What is polycythaemia?

A

An increase in circulating red cell concentration by a persistently raised haematocrit. This is defined by haematocrit exceeding 52% in males and 48% in females.

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5
Q

What is relative polycythaemia?

A

When there is a normal red cell mass but a decreased plasma volume.

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6
Q

What is absolute polycythaemia?

A

When there is an increased red cell mass.

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7
Q

What is polycythaemia vera?

A

A specific form which arises from a myeloproliferative neoplasm in the bone marrow causing an overproduction of RBCs.

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8
Q

Which gene is usually mutated (95%) in polycythaemia vera? What does it normally do?

A

Janus Kinase 2 (JAK2)
Stimulating signalling pathways to produce erythrocytes in response to EPO.
JAK2 mutation causes multipoint stem cells to survive longer and proliferate continuously.

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9
Q

What are consequences of polycythaemia vera?

A 
Thicker blood
Thrombosis
Haemorrhage (skin or GI tract)
Headache and dizziness
Plethora
Burning pain in the hands or feet
Pruritus
Splenic discomfort and splenomegaly
Gout
Arthritis

Can also transform into myelofibrosis or acute leukaemia.

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10
Q

How is polycythaemia managed?

A

Venesection where blood is taken to maintain a haematocrit of under 45%.

Aspirin as a blood thinner

Drugs to reduce overproduction

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11
Q

What is secondary polycythaemia?

A

Excess of red blood cells driven by increased EPO production.

It can be either physiological in response to tissue hypoxia or pathological.

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12
Q

Give examples of how secondary polycythaemia can arise.

A

Physiological:
Tissue hypoxia in chronic lung disease, right to left shunts, high altitude, or CO poisoning.

Abnormal/pathological:
Renal hypoxia where there is renal artery stenosis, Hepatocellular carcinoma, renal cell cancer, uterine tumours, phaeochromocytoma.

All these will increase EPO production.

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13
Q

Secondary polycythaemia can arise without physiological or pathological reason. Sometimes it is induced by intent, how?

A

By injection of EPO.

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14
Q

What is thrombocytosis?

A

An increase in platelet count.

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15
Q

How does thrombocytosis most commonly occur?

A

As a reaction to infection and inflammation.

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16
Q

What is another less common cause of thrombocytosis?

What is the thrombocytosis called in this case?

A

Myeloproliferative neoplasm where the thrombocytosis is called essential thrombocythaemia.

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17
Q

What is essential thrombocythaemia? What is it caused by?

A

Rare chronic blood cancer with overproduction of platelet by megakaryocytic in the bone marrow.
Most commonly caused by JAK2 mutation or mutation in the thrombopoietin receptors. Also CALR mutations.

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18
Q

What are the most common symptoms of essential thrombocythaemia?

A 
Numbness in extremities
Thrombosis
Disturbances in hearing and vision
Headaches
Burning pain in hands or feet
19
Q

If there is a raised thrombocyte count, what should you look for first?

A

Since essential thrombocythaemia is rare the first causes to exclude are:
Infection
Inflammation
Tissue injury
Haemorrhage
Cancer
Redistribution of platelets after splenectomy or in hyposplenism.

20
Q

How is essential thrombocythaemia managed?

A

Aspirin

Hydroxycarbamide

21
Q

What is primary myelofibrosis?

A

Myeloproliferative neoplasm where the proliferation of mutated haematopoietic stem cells. This causes reactive bone marrow fibrosis which will lead to replacement of marrow with scar tissue.
Often associated with JAK2 gene.
Mobilisation of mutated progenitor cells from bone marrow can also occur and these cells can colonise the liver and spleen leading to extramedullary haemopoiesis.

22
Q

What is secondary myelofibrosis?

A

Myelofibrosis as a result of polycythaemia vera or essential thrombocythaemia.

23
Q

What are symptoms of myelofibrosis?

A 
Hepatomegaly
Splenomegaly
Fatigue
Weight loss due to early satiety
Splenic infarction
Fever
Increased sweating
Portal hypertension
24
Q

How is myelofibrosis managed?

A 
Hydrocarbadmide
Folic acid
Allopurinol
Blood transfusions
Splenectomy
Ruxolitinib (JAK2 inhibitor)
25
Q

What is the main difference between acute and chronic leukaemia?

A

Acute rapidly cause bone marrow failure due to large numbers of immature blast cells overwhelming the ability of the tissue to produce mature blood cells.

Chronic are more often slow to cause symptoms and may even be picked up as a chance finding on a blood count.

26
Q

Explain Chronic myeloid leukaemia.

A

Unregulated growth of myeloid cells in bone marrow leading to accumulation of mature granulocytes (mainly neutrophils) but also excess of all myeloid series from blast to mature. Immature cells can also be found in the blood.

27
Q

How does chronic myeloid leukaemia most commonly arise?

A

Due to chromosomal translocation called the Philadelphia chromosome. (Reciprocal translocation between chromosome 9 and 22) This switches on a receptor tyrosine kinase which drives proliferation. Inhibits apoptosis as well.
Usually present in adult and not in children.

28
Q

What are some symptoms of chronic myeloid leukaemia?

A

Splenomegaly
Hyperviscosity (sticky blood)
Bone pain

29
Q

How is chronic myeloid leukaemia usually treated?

A

Drugs which inhibits the ATP-binding site of the tyrosine kinase. (Tyrosine kinase inhibitor)

30
Q

Define pancytopenia.

A

Reduction in white cells, red cells and platelets (all cells).

31
Q

Pancytopenia can arise from two mechanisms. Which? Which is the most common?

A

Either a reduced production of cells (most common)
Or
Increased removal of cells such as autoimmune destruction, splenic pooling in hypersplenism and splenomegaly but also haemophagocytosis (very rare).

32
Q

Give causes of pancytopenia arising from reduced production of cells.

A 
B12/folate deficiency.
Drugs
Viruses like EBV, Hep, HIV and CMV
Cancer in bone marrow
Marrow fibrosis
Radiation
Idiopathic aplastic anaemia
Congenital bone marrow failure like Fanconi's anaemia
33
Q

What is aplastic anaemia?

A

Rare diseases resulting in damage to bone marrow and haematopoietic stem cells causing pancytopenia.

Can be caused by genes, autoimmune disease or exposure to chemical, drugs or radiation.

34
Q

What is thrombocytopenia?

A

Low levels of platelets.

35
Q

There are two main groups of thrombocytopenia. Which?

A

Acquired (most common) and inherited.

36
Q

What are the three causes of acquired thrombocytopenia?

A

Decreased platelets production, increased consumption or increased destruction.

37
Q

What are symptoms of severe thrombocytopenia?

A 
Easy bruising
Petechiae, purpura (purple spots)
Mucosal bleeding
Severe bleeding after trauma
Intracranial haemorrhage
38
Q

What is immune thrombocytopenic purpura?

A

Autoantibodies that attach to the platelets causing phagocytosis and destruction of the cells.

39
Q

What is secondary immune thrombocytopenic purpura?

A

When rheumatoid arthritis, systemic lupus or and underlying lymphoid cancer such as lymphoma or leukaemia or HIV causes thrombocytopenic purpura.

40
Q

How is immune thrombocytopenic purpura treated?

A

By immunosurpressors like corticosteroids or intravenous immunoglobulin first line.

41
Q

Why would platelet transfusion not work in immune thrombocytopenic purpura?

A

Because the transfused platelets would be destroyed too.

42
Q

Give examples of thrombocytopenias due to decreased platelet production.

A 
B12/folate deficiency
Acute leukaemia
Aplastic anaemia
Liver failure (less TPO)
Sepsis
43
Q

Give examples of thrombocytopenias due to increased consumption.

A

Massive haemorrhage
DIC
Thrombotic thrombocytopenic purpura

44
Q

Give examples of thrombocytopenias due to increased destruction.

A

Autoimmune thrombocytopenic purpura
Drug induced
Hypersplenism reposting in increased destruction and splenic pooling of thrombocytes.

MEH (22 decks)

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