Haemopoiesis gone wrong

Question 1

What are myeloproliferative disorders?

Answer 1

• group of disease of bone marrow where excess cells are produced
• genetic mutations affecting precursors of myeloid lineage = dysregulation at multipotent haematopoietic stem cell

Question 2

What are the 4 types of myeloproliferative disorders?

Answer 2

1) Polycythaemia Vera
2) Essential thrombocythaemia
3) Primary myelofibrosis
4) Chronic myeloid leukaemia

Question 3

What are some clinical features of Myeloproliferative disorders?

Answer 3

• overproduction of 1 or more blood elements
• hypercellular marrow/marrow fibrosis
• thrombic and/or haemarrhagic diatheses
• extra-medullary haemopoiesis
• potential to transform to acute leukemia

Question 4

What is polycythaemia?

Answer 4

increase in circulating red cell concentration with a persistently raised haematocrit
-can be:
+relative = normal red cell mass with decreased plasma volume
+absolute = increased red cell mass

Question 5

What is polycythaemia vera?

Answer 5

A primary absolute polycythaemia

Question 6

What are some features of polycythaemia vera?

Answer 6

• venous thrombosis
• haemorrhage into skin or GI
• pruritus
• splenic discomfort
• gout

Question 7

How is polycythaemia vera managed?

Answer 7

1) Venesection to maintain Hct < 0.45
2) Aspirin = anti-platelet effect to avoid arterial thrombosis
3) Cytoreduction agents

Question 8

What are the causes of secondary (absolute) polycythaemia?

divided into physiologically appropriate, inappropriate and others

Answer 8

Appropriate = living at high altitudes, COPD
Inappropriate = heptocellular carcinoma, renal cancer, uterine tumours
Other = performance sports

Question 9

What is essential thrombocythaemia?

Answer 9

overproduction of platelets by megakaryocytes in the BM

Question 10

List common symptoms of essential thrombocythaemia

Answer 10

• numbness
• disturbance in hearing and vision
• headaches
• burning pain in hands or feet
• thrombosis

Question 11

How is essential thrombocythaemia managed?

Answer 11

• Aspirin
• hydroxycarbomide = returns platelet count
• Cardiovascular risk factors should be aggressively managed

Question 12

What is myelofibrosis?

Answer 12

Proliferation of mutated haemopoietic stem cells resulting in reactive bone marrow fibrosis = replaces marrow with scar tissue

Question 13

What are the clinical features of myelofibrosis?

Answer 13

• Bruising
• Fatigue
• Weight loss
• Fever
• Sweating
• Hepatosplenomegaly

Question 14

How is myelofibrosis managed?

Answer 14

-Hydroxycarbamide
-Folic acid
Blood transfussion
-Ruxolitinib = JAK2 inhibitor

Question 15

What is chronic myeloid leukemia?

Answer 15

Unregulated growth of myeloid cells in BM = accumulation of mature granulocytes (mainly neutrophils)

Question 16

How does chronic myeloid leukaemia present?

Answer 16

• Symptomatic splenomegaly
• Hyperviscosity
• Bone pain
• Associated with philadelphia chromosome (via reciprocal translocation)

Question 17

What are the three ‘underproduction’ disorders?

Answer 17

1) Pancytopenia
2) Aplastic anaemia
3) Thrombocytopenia

Question 18

What is Panyctopenia?

Answer 18

Reduction white cells, red cells and platelets

Question 19

What are the causes of pancytopenia?

Answer 19

• B12/folate deficiency
• BM infiltration by malignancy
• Marrow fibrosis
• Radiation
• Drugs
• Increased removal (immune destruction, splenic pooling, haemophagocytosis = chewing up of cells in BM)

Question 20

What is aplastic anaemia?

Answer 20

Pancytopenia with a hypocellular BM in absence of an abnormal infiltrate

Question 21

What is thrombocytopenia?

Answer 21

abnormally low levels of platelets

Question 22

What are the consequences of thrombocytopenia?

Answer 22

• Easy bruising
• Petechiae/purpura
• Mucosal bleeding
• Severe bleeding

Question 23

How is thrombocytopenia acquired?

Answer 23

• Decreased platelet production (B12/Folate deficiency, liver failure, sepsis)
• Increased platelet consumption (massive haemorrhage, DIC)
• Increased platelet destruction (autoimmune thrombocytopenia purpura, drug induced e.g. heparin)

Question 24

What is immune thrombocytopenia purpura and how is it treated?

Answer 24

• Common cause of thrombocytopenia
• Autoantibodies against glycoprotein IIb/IIa + GPlb/IX
• Treated with immunosuppressants or intravenous immunoglobulin