When Haemopoiesis Goes Wrong

Question 1

What does overproduction of blood cells cause?

Answer 1

Myeloproliferative disorders/neoplasms

Question 2

What does underproduction of blood cells cause?

Answer 2

Aplastic anaemia - all cells
Thrombocytopenia - platelets

Question 3

Causes of overproduction of cells

Answer 3

Damage to bone marrow
Abnormal hormone signalling

Question 4

Outline myeoproliferativee neoplasms

Answer 4

Overproduction due to disease in bone marrow
Often caused by genetic mutations in JAK2 gene

Question 5

Types of myeloproliferative disorders

Answer 5

polycynthaemia vera
essential thrombocythaemia
primary myelofibrosis
chronic myeloid leukaemia

Question 6

Outline polycythaemia

Answer 6

Excess erthyrocytes
Diagnosed by high haematocrit 52% men 48% women

Question 7

Causes of polycythaemia

Answer 7

Relative - decreased plasma volume
Absolute - increased erythrocyte count

Question 8

Outline absolute polycythaemia

Answer 8

Increase in number of erythrocyte
primary - abnormality in bone marrow
- e.g polycythaemia vera ONLY
secondary - increased EPO
- response to hypoxia

Question 9

Outline polycythaemia Vera

Answer 9

Absolute primary polycythaemia
A myleoproliferative neoplasm
Mutation of JAK2
Excess erythrocytes due to abnormality in bone marrow

Question 10

What does a mutation in JAK2 gene do?

Answer 10

Makes blood cell sin bone marrow hypersensitive to EPO
Causes proliferation of RBCs

Question 11

Clinical features of polycynthaemia Vera

Answer 11

Thrombosis
Haemorrhage
Dizziness
Pruritis
Gout
Splenomegaly

Question 12

Management of polycythaemia Vera

Answer 12

Venesection to maintain haematoocrit to <45%
Aspirin 75mg
Manage CVS risk factors

Question 13

What is thrombocytosis?

Answer 13

Increased platelet count

Question 14

Outline essential thrombocythaemia

Answer 14

• A myleoproliferative neoplasm
• Over production of megakaryocytes > excess platelets in blood
• Mutation in JAK2 gene or thrombopoietin receptor

Question 15

Symptoms of essential thrombocythaemia

Answer 15

Numbness in extremities
Thrombosis
Headaches
Issues with vision + hearing

Question 16

Treatment of essential thrombocythaemia

Answer 16

Low risk for bleeding - aspirin
High risk for bleeding - hydroxycarbamide

Question 17

Types of thrombocytosis

Answer 17

• primary - essential thrombocythaemia
• secondary - normal bone marrow response to extrinsic factors e.g. infection
• redistributional: platelets redistributed from splenic pool into blood

Question 18

Outline primary myleofibrosis

Answer 18

Proliferation of mutated haemopoietic stem cells
Results in reactive bone marrow fibrosis
Leads to collagen deposition >pancytopenia + schistocytes + tear drop cells
Mutation in JAK2 gene (+ CALR and MPL gene)

Question 19

What is pancytopenia?

Answer 19

Decrease in levels of all blood cells

Question 20

Symptoms of primary myelofibrosis

Answer 20

Hepatosplenomegaly
Bruising
Fatigue
Weight loss
Fever + sweating
Portal hypertension

Question 21

Types of leukaemia

Answer 21

Acute or chronic
Myeloid - from myeloid lineage > RBCs, platelets, monocytes, granulocytes
Lymphoid - from lymphoid lineage > lymphocytes, B+ T cells

Question 22

Outline chronic myeloid leukaemia

Answer 22

• Unregulated growth of myeloid cells in bone marrow > accumulation of granulocytes - many white cells
• mutation on chromosome 9 and 22 via reciprocal translocation - Philadelphia chromosome
• switches on a receptor tyrosine kinase > proliferation

Question 23

Symptoms of chronic myeloid leukaemia

Answer 23

Splenomegaly
Sticky blood
Bone pain

Question 24

Outline aplastic anaemia

Answer 24

• inability of stem cells to generate mature blood cells
• results in bone marrow + haemopoetic stem cell damage
• leads to pancytopenia

Question 25

Causes of aplastic anaemia

Answer 25

Genetic Autoimmune Exposure to chemical, medication + dugs

Question 26

Treatment of aplastic anaemia

Answer 26

Immunosuppressants Bone marrow transplant - risk of new WBCs attacking body

Question 27

Causes of pancytopenia

Answer 27

Splenic pooling Haemophagocytosis Immune destruction B12/folate deficiency Infection Drugs Idiopathic aplastic anaemia Primary myelofibrosis

Question 28

What is thrombocytopenia?

Answer 28

- low platelet count

Question 29

Outline acquired thrombocytopenia causes

Answer 29

**decreased platelet production**: - B12/folate deficiency - cant make megakaryocytes - liver failure - less thrombopoetin **increased platelet consumption** - massive haemorrhage - DIC - thrombic thrombocytopenia purpura **increased platelet destruction**: - Hypersplenism - splenic pooling + more destruction - drug induced - autoimmune thrombocytopenia

Question 30

What are the three causes of acquire thrombocytopenia?

Answer 30

- decreased platelet production - increased platelet consumption - increased platelet destruction

Question 31

Symptoms of thrombocytopenia

Answer 31

Bleeding in gums Nosebleeds Petechiae

Question 32

Outline thrombotic thrombocytopenia purpura

Answer 32

- Increased blood clotting in small vessels > decreased platelets - caused by platelet activation due to endothelial damage - may schistocytes

Question 33

Outline immune thrombocytopenia purpura

Answer 33

Autoimmune disease Immune platelet destruction Caused by anti-platelet autoantibodies

Question 34

Treatment of immune thrombocytopenia purpura

Answer 34

Immunosuppression NOT platelet transfusion - will get destroyed

Question 35

What drug is used to treat chronic myeloid leukaemia?

Answer 35

**Imatinib** Tyrosine kinase inhibitor (TK normally drives white cell proliferation)

Question 36

Name the triad of conditions in Felty’s syndrome

Answer 36

RA Neutropenia Splenomegaly