Myeloproliferative neoplasms - when haemopoieis goes wrong

Question 1

What are MPNs

Answer 1

Group of diseases of the bone marrow where excess cells are produced arising from genetic mutations in precursors of myeloid lineage in the bone marrow

Question 2

What are the main types of MPNs

Answer 2

Polycythaemia vera

Essentail thrombocytheaemia

Primary myelofibrosis

Chronic myeloid leukaemia

Question 3

What is polycythaemia and what are the two types

Answer 3

It is a disease wher the volume percent of erythrocytes in the blood (haematocrit) exceeds 52% (males) or 48% (females)

Absolute polycythaemia - increases in erythrocytes

Relative polycythaemia - decrease in plasma volume

Question 4

How is polycythaemia characterisated based on its cause

Answer 4

Relative - decreased plasma volume

Absolute - increased RBC number

• Primary - abnormality in the bone marrow
• Secondary - increased levels of EPO
  
  • Physiological response to hypoxia
  • Abnormal production

Question 5

What is polycythaemia vera

Answer 5

Polycythaemia caused by myeloproliferative neoplasm in the bone marrowing causing overproduction of erythrocytes

Caused by mutation in Janus Kinase 2 (JAK2) gene

Cells with mutation in JAK2 survive longer and proliferate continuously

Question 6

What are the clinical features of polycythaemia vera

Answer 6

Result from blood being thicker and include:

Thrombosis

Haemorrhage

Headache and dizziness

Plethora

Burning pain in hands or feet

Pruritus

Splenic discomfort - splenomegaly

Gout

Arthritis

Question 7

Treatment of polycythaemia vera

Answer 7

Phlebotomy to maintin haematocrit below 45%

Aspirin - anti-platelet

Cytoreduction

Question 8

What are the types of secondary polycythaemia

Answer 8

Physiologically appropriate - increased EPO production is caused by recognisable problem

Physiologically inappropriate - increased EPO production not associated with pathology that would cause it to rise

Question 9

What is thrombocytosis and what are its common causes

Answer 9

Increase in platelet count compared to normal range

Common causes:

Infection

Inflammation

Tissue injury

Haemorrhage

Cancer

Redistribution of platelets - post-splenectomy and hyposplenism

Question 10

What is essential thrombocythaemia and how is it caused

Answer 10

Thrombocytosis caused by a myeloproliferative neoplasm where there is overproduction of platelets by megakaryocytes

Half of the cases are caused by JAK2 mutations

Question 11

What are the common symptoms of essential thrombocythaemia

Answer 11

Numbness in extremities

Thrombosis

Disturbances in hearing and vision

Headaches

Erythromegelalgia (burning pain in hands/feet)

Question 12

What is thrombocytopenia

Answer 12

Condition where there is an abnormally low level of platelets

Question 13

How can platelet disorders be classified

Answer 13

Quantitative - low number

Qualitative - defective number, usually normal number

Question 14

How can thrombocytopenia be classified

Answer 14

Inherited (rare)

Acquired

• Decreased platelet count
• Increased platelet consumption
• Increased platelet destruction

Question 15

When do you get and what are the consequences of thrombocytopenia

Answer 15

Symptoms occur when platelet count >30

Easy bruising

Petechiae

Purpura

Mucosal bleeding

Severe bleeding after trauma

Intercranial haemorrhage

Question 16

What is immune thrombocytopenic purpura (ITP)

Answer 16

Autoimmune disease characterised by isolated thrombocytopenia - can have acute or chronic course

Mainly due to atni-platelet auto-antibodies against glycoprotein

Question 17

What are the causes of ITP

Answer 17

Acute infection

Associated autoimmune diseases - RA or systemic lupus erythematosus

Underlying lymphoid cancers

HIV

Question 18

What is primary myelofibrosis

Answer 18

Myeloproliferative neoplasm where proliferation of mutated haematopoietic stem cells results in reactive bone marrow fibrosis leading to replacement of marrow with scar tissue. Usually caused by JAK2 mutation

Leaves little space for haemopoiesis so extramedullary haemopoiesis takes place

Question 19

What is secondary myelofibrosis

Answer 19

Where myelofibrosis has developed as a consequence of polycythaemia vera or essential thrombocythaemia

Question 20

What are the symptoms of primary/secondary myelofibrosis

Answer 20

Heaptomegaly

Splenomegaly

Fatigue

Weight loss

Fever

Increased sweating

Portal hypertension

Question 21

What is the difference between chronic and acute leukaemias

Answer 21

Acute - rapidly cause bone marrow failure due to larger numbers of immature blast cells overwhelming ability of tissue to produce mature blood cells

Chronic - slow to cause symptoms and often have differentiation of the cells

Question 22

What is chronic myeloid leukaemia

Answer 22

Unregulated growth of myeloid cells in the bone marrow leading to accumulation of mature granulocytes and myelocytes in the blood

Caused by philadelphia chromosomes (reciprocal translocation between chromosomes 9 and 22)

Translocation results in an oncoprotein (BCR-ABL) with tyrosine activity that causes proliferation, differentiation and inhibition of apoptosis

Question 23

How is chronic myeloid leukaemia treated

Answer 23

Drug used which inhibits ATP-binding site on tyrosine kinase

Question 24

What is pancytopenia and classify how it it caused

Answer 24

It is a reduction in white cells, red cells and platelets

Either caused by increased removal or decreased production

Question 25

Pancytopenia - increased removal causes:

Answer 25

Immune-destruction

Splenic pooling

Haemophagocytosis

Question 26

Pancytopenia - reduced production causes:

Answer 26

B12/folate deficiency

Bone marrow infiltrated by malignancy

Marrow fibrosis

Radiation

Drugs

Viruses

Idiopathic aplastic anaemia

Congenital bone marrow failure

Question 27

What is aplastic anaemia

Answer 27

Where the bone marrow cannot produce mature blood cells, caused by damage to the bone marrow and haematopoietic stem cells leading to pancytopenia

Question 28

What causes aplastic anaemia

Answer 28

Genetic causes

Auto immunity

Exposure to chemicals, drugs or radiation