When Haemopoiesis Goes Wrong

Question 1

What is myeloproliferative neoplasms

Answer 1

A group of diseases of the bone marrow in which excess cells are produced. They arise from genetic mutations in the precursors of the myeloid lineage in the bone marrow,

Question 2

What are the four types of major myeloproliferative neoplasms ?

Answer 2

1) polycythaemia Vera
2) essential thrombocythaemia
3) primary myelofibrosis
4) chronic myeloid leukaemia

Question 3

What is polycythaemia?

Answer 3

A disease state in which the volume percent of erythrocytes in the blood exceeds 52% ( M) or 48% ( F)

Question 4

What is absolute polycythaemia?

Answer 4

Where the increase in the volume percent of RBC arises from an increase in the number of erythrocytes

Question 5

What is relative polycythaemia?

Answer 5

There increase in volume percent of RBC increases because there is a decrease in plasma volume,

Question 6

What is polycythaemia Vera? - Primary polycythaemia

Answer 6

A specific form of polycythaemia which arises from a myeloproliferative neoplasms ( a type of blood cancer ) in the bone marrow resulting in overproduction of erythrocytes.

• 95% of cases are caused by a mutation of the gene coding for JAK2 ( Janus kinase 2) - a tyrosine kinase whose normal function is to stimulate signalling pathways leading to RBC production in response to EPO. Multipotent stem cells harbouring the JAK2 mutation survive longer and proliferate continuously.

Question 7

What are the clinical features associated with polycythaemia Vera resulting from the blood being thicker ?

Answer 7

1) thrombosis ( venous and arterial )
2) haemorrhage
3) burning pain in hands or feet
4) gout
5) may transform into myelofibrosis

Question 8

What is the treatment of polycythaemia Vera ?

Answer 8

1) phlebotomy ( act of drawing blood) - to main haematocrit below 45%.
2) aspirin due to its anti platelet effects may be prescribed.
3) cytoreduction agents such as hydroxycarbamide which is an oral antimetabolite that inhibits DNA synthesis - this should only be given if the patient has poor tolerance to venesection ( drawing blood ) , shows symptom if or progressive splenomegaly.

Question 9

What is secondary polycythaemia?

Answer 9

Caused by an increased of erythpoiten

Question 10

What is the cause of the increase in EPO ?

Answer 10

1) living at high altitude
2) chronic hypoxia ( COPD, heavy long term cigarette use , cyanotic heart disease )
3) renal disease
4) tumours secreting EPO.

Question 11

What is thrombocytosis?

Answer 11

An increase in the platter count compared to normal range of a person of the same gender and age.

Question 12

What is essential thrombocythaemia ?

Answer 12

An increase in platelet count due to myeloproliferative Neoplasms.

• this is characterised by the overproduction of platelets by megakarytocytes in the bone marrow.
• around half of the cases of essential thrombocythaemia are caused by the same JAK2 mutations. Mutations in the thrombopoietic receptor can also result in the disease.

Question 13

What are the symptoms of thrombocythaemia?

Answer 13

Numbness
Thrombosis

Disturbances in hearing and vision

Headaches

Burning pain in hands and feet

Question 14

How to treat patients with essential thrombocythaemia?

Answer 14

Low risk patients - aspirin

2) high risk : hydroxycarbamide which helps to reduce platelet count.

Question 15

What is secondary thrombocythaemia?

Answer 15

Normal bone marrow response to extrinsic stimulus eg infection or inflammation

Question 16

What is thrombocytopenia?

Answer 16

Abnormal level of platelets.

Question 17

What do we classify thrombocytopenia into ?

Answer 17

1) acquired ( common )

2) inherited ( rare syndrome )

Question 18

Individuals with a low platelet count may experience wat ?

Answer 18

Bleeding gums

Nosebleeds

Women may have longer or heavier menstrual periods

Bruising

Question 19

What are examples of acquired thrombocytopenia?

Answer 19

1) decreased plat,eg production
2) Increased platelet consumption
3) Increased platelet destruction

Question 20

What are causes of decreased platelet production

Answer 20

• B12 or folate deficiency
• sepsis
• liver disease

Question 21

What causes increased platelet consumption ?

Answer 21

Massive haemorrhage

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Question 22

Immune thrombocytopenia purpura

Answer 22

Autoimmune disease where anti-platelet auto antibodies against platelets and megakaryocytes.

• important that doctors recognise this as severe as treatments options differ eg immunosuppressive drugs , corticosteroids

Question 23

What is primary myelofibrosis

Answer 23

Is a myeloproliferative neoplasms where proliferation of mutated hematopoietic stem cells results in reactive bone marrow fibrosis eventually leading to scarring ( collagen deposition )

• mutations in the JAK2 gene are often associated with the disease.

Question 24

Why is spleen enlarged in primary myelofibrosis?

Answer 24

Extramedullary haemopoiesis

Question 25

Secondary myelofibrosis

Answer 25

Disease develops as a consequence of polycythaemia vera or essential thrombocythaemia

Question 26

What are symptoms myelofibrosis?

Answer 26

• weight loss
• increased sweating
• bruising
• fever

Question 27

Treatment options of myelofibrosis

Answer 27

• ruxolitnib an inhibitor of JAK2