When Haemopoesis Goes Wrong

Question 1

What is polycythaemia is

Answer 1

Volume percent of erythrocytes in blood is high. Exceeds 52% in males and 48% in females. (High haemocrit

Question 2

Causes of polycythaemia

Answer 2

Can be absolute where is caused by increased RBC or can be relative where caused by increase in plasma

Question 3

What causes absolute polycythaemia

Answer 3

Primary cause- polycythaemia Vera which is myeloproliferative neoplasm in bone marrow usually due to JAK2 mutation which causes multipotent stem cells to survive longer and proliferate continuously

Secondary - EPO increase due to disease e.g renal carcinoma or in response to hypoxia e.g in high altitude

Question 4

Clinical features and symptoms of polycythaemia Vera

Answer 4

Blood is thicker and higher percentage of haematocrit. 
Thrombosis 
Haemorrhage 
Headache 
Plethora 
Burning in hands and feet 
Puritus
Gout
Arthritis

Question 5

Treatment of polycythaemia Vera

Answer 5

Phlebotomy to maintain haematocrit below 45% (removal of blood)
Aspirin due to its antiplatelet effect
Hydroxycarbamide - inhibits DNA synthesis for synthesis of new RBC

Question 6

What is essential thrombocythaemia

Answer 6

Increase in platelets.

Question 7

Causes of thrombocythaemia

Answer 7

Primary - myeloproliferative neoplasm where there is overproduction of platelets by megakaryocytes. Most have JAK2 mutations. Referred to as ESSENTIAL THROMBOCYTHAEMIA
Can also be due to mutations in thrombopoietin receptor

Secondary- normal bone response to extrinsic stimulus e.g infection

Question 8

Symptoms of essential thrombocythaemia

Answer 8

Numbness of extremities
Thrombosis
Headaches
Burning pain in hands and feet (erythromelagia)

Question 9

Treatment of essential thrombocythaemia

Answer 9

Low risk patients- aspirin to lower platelet count

High risk - hydroxycarbomide treatment

Question 10

What is and what causes inherited thrombocytopenia

Answer 10

Rare inherited syndrome where have low platelet count

Question 11

What is and what causes acquired thrombocytopenia

Answer 11

Low platelet count due to
Decrease in platelet production
Increase in consumption of platelets
OR increase in destruction of platelets

Question 12

Symptoms of acquired thrombocytopenia

Answer 12

Bleeding gums, nose bleeds, heavier and longer menstrual periods, spontaneous bleeding under skin called petechia

Question 13

What is primary myelofibriosis

Answer 13

when mutated haematopoeitic stem cells result in bone marrow fibrosis and laying down of scar tissue. also some mutated progenitor cells may leave bone marrow and colonise liver and spleen causing extra medullary heamopoeisis

Question 14

what is secondary myelofibrosis

Answer 14

disease has developed as a consequence of polycythaemia vera or essential thrombocythaemia.

Question 15

cause of myelofibrosis

Answer 15

mutations in JAK 2 gene often associated with disease

Question 16

side effects of myelofibrosis

Answer 16

hapatosplenmogaly - due to extramedullary hameatopoiesis
bruising
fatigue
fever
increased sweating
portal hypertension (due to narrowing of sinusoids in liver from extra medullary haempatopoeisis)

Question 17

treatment options for myelofibrosis

Answer 17

hydroxycarbamide
folic acid
allopurinol 
blood transfusions 
splenectomy 
ruxolitinib - inhibitor of JAK 2 reduces spleen volume

Question 18

what is chronic myeloid leukaemia

Answer 18

a leukaemia which is more slow to cause symptoms. may just be picked up by chance on a blood count. its the unregulated growth of myeloid cells in the bone marrow leading to the accumulation of mature granulocytes (mainly neutrophils) as well as myelocytes (bone marrow cell) in blood.

Question 19

what causes chronic myeloid leukaemia

Answer 19

often associated with chromosomal translocation called Philadelphia chromosome between chromosome 9 and 22. = oncogenic gene fusion with tyrosine kinase activity that results in proliferation, differentiation and inhibition of apoptosis.

Question 20

treatment of chronic myeloid leukaemia

Answer 20

drugs which inhibit ATP binding site of tyrosine kinase. this drugs has rapidly improved survival rates

Question 21

what is aplastic anaemia

Answer 21

rare disease that results in damage to bone marrow and haematopoitic stem cells leading to pancytopenia (deficiency in all 3 cell types)

Question 22

causes of aplastic anaemia

Answer 22

genetics, autoimmunity, exposure to chemicals, drugs or radiation