Haemopoiesis and Haemolytic Anaemia

Question 1

Foetal haemoglobin

Answer 1

2 alpha and 2 gamma globin chains, should be less than 1% in adults, it is the main form before birth

Question 2

HbA

Answer 2

2 alpha, 2 beta chains

Question 3

HbA2

Answer 3

2 alpha, 2 delta

Question 4

Definition of haemoglobinopathies

Answer 4

inherited disorders in haemoglobin, typically autosomal recessive

Question 5

Thalassemia

Answer 5

Reduced or absent expression of normal globin chains

Question 6

Sickle cell disease

Answer 6

Abnormal globin chain variants with altered function

Question 7

a-Thalassemia

Answer 7

Humans have 4 a-globin genes, 2 on each chr16

Question 8

1 deleted alpha globin gene

Answer 8

Silent carrier state, no symptoms, carrier of disease

Question 9

2 a-globin deleted

Answer 9

a-Thalassemia trait, minimal or no anaemia, microcytosis and hypochromia in RBC

Question 10

3 a-globin genes deleted

Answer 10

Haemoglobin H disease, moderately severe, microcytoc, hypochromic anaemia with target cells and Heinz bodies

Question 11

4 a-globin genes deleted

Answer 11

Hydrops fetalis, severe, usually results in intrauterine death

Question 12

Consequences of Thalassemia

Answer 12

Extramedullary haemopoiesis resulting in splenomegaly, hepatomegaly, impaired growth, iron overload

Question 13

Thalassemia treatments

Answer 13

• Red cell transfusion from childhood
• Folic acid (supports erythropoiesis)
• Stem cell transplant

Question 14

Sickle cell disease

Answer 14

Autosomal recessive resulting in mutation of beta globin gene

Question 15

Why is sickle cell disease a problem?

Answer 15

In low oxygen state, irreversibly sickled cells that are less deformable can get stuck in small blood vessels

Question 16

Symptoms of sickle cell disease

Answer 16

Stroke, skin ulcers, acute chest syndrome

Question 17

Autoimmune haemolytic anaemias

Answer 17

Caused by autoantibodies binding to red cell membrane proteins, spleen recognises these as abnormal -> reduced life span of RBC

Question 18

Myeloproliferative neoplasms

Answer 18

Overproduction of one or several blood elements with dominance of a transformed clone

Question 19

Cause of myeloproliferative neoplasms

Answer 19

Point mutation in one copy of JAK2 gene

Question 20

JAK2 mutation

Answer 20

Normal activated my EPO on receptor of RBC surface, mutated is activated without EPO binding

Question 21

Polycythaemia

Answer 21

Increase in circulating RBC concentration, usually have raised haemotocrit

Question 22

Polycythaemia vera

Answer 22

Usually in older patients, bone marrow overproduction due to genetic mutation

Question 23

Clinical features of polycythaemia vera

Answer 23

• arterial/venous thrombosis
• splenomegaly
• gout

Question 24

Secondary polycythaemia

Answer 24

Caused by increased levels of erythropoietin

Question 25

Symptoms of secondary polycythaemia

Answer 25

Chronic lung disease, renal hypoxia, renal cell cancer

Question 26

Cause of essential thrombocythaemia

Answer 26

Associated with JAK2 and CAL-R mutations

Question 27

Clinical features of thrombocythaemia

Answer 27

Increased platelets in blood, increase in megakaryocytes, thrombotic events

Question 28

Myelofibrosis

Answer 28

Genetic mutation in JAK2, excess of platelet derived growth factor, causes increased reticulin, heavily fibrotic bone marrow

Question 29

Myelofibrosis clinical features

Answer 29

Massive splenomegaly or hepatomegaly, RBC look like tear drops in blood film

Question 30

Primary myelofibrosis

Answer 30

Clonal baemopoietic stem cell proliferation, may be end result of polycythaemia vera or essential thrombocythaemia

Question 31

Clinical features of primary myelofibrosis

Answer 31

Fatigue, sweats, weight loss, early satiety due to splenomegaly

Question 32

Chronic myeloid leukaemia

Answer 32

High white cell count, splenomegaly, bone pain or hyperviscosity (sticky blood)

Question 33

BCR:ABL1 fusion

Answer 33

Translocation of Abl gene on chr9 and Bcr on chr22 to make a Philadelphia chromosome that drives proliferation

Question 34

Tyrosine kinase inhibitors

Answer 34

Used to treat myeloproliferative disorders