haematology: hemoglobinopathies

Question 1

Where is globin chain genes found

Answer 1

Chromosome 11 & 16

Question 2

What is an example of quantitative hemoglobinopathies

Answer 2

Thalassemia

Question 3

What is thalassemia

Answer 3

Genetic disorder with abnormalities of hemoglobin production resulting in reduced rate of synthesis of either a-/b-chain

Question 4

What is a-thalassemia

Answer 4

a-globin gene defective leading to little or none a globins on chromosome 16

Question 5

What is b-thalassemia

Answer 5

b-globin gene defective leading to little or none a globins on chromosome 11

Question 6

What type of genetic condition is thalassemia

Answer 6

Autosomal recessive

Question 7

What is the 4 pathogenesis of thalassemia

Answer 7

1. Oxidative injury: due to unpaired a & b chains with heme more susceptible to oxidation
2. Membrane damage
3. Abnormal hydration: b dehydrated & a hyper-hydrated
4. Reduced deformability

Question 8

What is the mechanism of anemia in thalassemia

Answer 8

Ineffective hemopoiesis
Hemolysis

Question 9

What is a silent carrier in a-thalassemia

Answer 9

Loss of one globin gene
Normal phenotype

Question 10

What is thalassemia trait in a-thalassemia

Answer 10

Loss of two globin gene
Asymptomatic with mild microcytic anemia

Question 11

What is HbH in a-thalassemia

Answer 11

Loss of three globin gene
Mild to moderate microcytic anemia

Question 12

What is Hb Barts in a-thalassemia

Answer 12

Loss of all globin chains
Hydrops fetalis & incompatible with life

Question 13

What is b-thalassemia minor/trait

Answer 13

Loss or mutation in one gene
Normal phenotype
Mild anemia

Question 14

What is non-transfusion dependent thalassemia in b-thalassemia

Answer 14

Loss of one gene or mutation in both genes
Only require transfusions in periods of stress
Present at 2-4 years

Question 15

What is transfusion dependent in b-thalassemia

Answer 15

Mutation or loss of both genes
Requires transfusions
Present 6-12 months

Question 16

What is the 6 clinical feature of thalassemia

Answer 16

1. Bone problems: overactive bone marrow leading to expansion & bone changes
2. Iron overload: frequent blood transfusions & increased iron absorption causing damage to organs
3. Anemia & fatigue: low Hb
4. Chronic hemolysis: iron overload, leg ulcers, gallstones & thrombosis
5. Splenomegaly: work overtime to remove abnormal RBC
6. Growth & puberty issues: poor oxygen delivery & nutritional deficiencies

Question 17

How is thalassemia diagnosed

Answer 17

FBC for microcytic hypochromic anemia & raised RCC
Hemoglobin electrophrosis
Genetic testing

Question 18

What is the treatment for thalassemia

Answer 18

1. Supportive: blood transfusions & iron chelation, monitoring complication & genetic counselling
2. Specific: stem cell transplants & gene therapy

Question 19

What is an example of qualitative hemoglobinopathies

Answer 19

Sickel cell anemia

Question 20

What is sickle cell anemia

Answer 20

Group of hemoglobin disorders resulting from inheritance of sickle B-globin gene
Due to a change in a single base pair

Question 21

What is the pathogenesis behind sickle cell anemia

Answer 21

HbS molecule polymerize

Question 22

What 3 factors increases polymerization

Answer 22

Deoxygenation
Higher HbS concentration
Acidosis

Question 23

What 4 factors decrease polymerization

Answer 23

Direct: increase HbF & HbA2
Indirect: a-thalassemia & hydration

Question 24

What is the 4 consequences of polymerization

Answer 24

1. RBC membrane damage
2. Hemolysis (intra- & extravascular)
3. Veno-occlusion
4. Hypercoagulable state

Question 25

What is 4 characteristic differences between a normal cell vs sickle cell

Answer 25

**Normal cell:** disc shaped, flexible, easily flow through small blood vessels & 120 days life span **Sickle cells:** banana shaped, rigid, stuck in small blood vessels & shortened lifespan

Question 26

When does sickle cell disease develop

Answer 26

Before age of 6 years but usually after 3-6 months when production of HbS increase & HbF decrease

Question 27

What is clinical features of sickle cell disease

Answer 27

Splenic sequestration, chest pain, risk of sepsis, Howell Jolly bodies with target cells

Question 28

What is the diagnostic tests for sickle cell

Answer 28

FBC, peripheral smear, hemoglobin electrophoresis & HPLC

Question 29

What is the treatment of sickle cell disease

Answer 29

1. **Symptomatic:** pain, antibiotics, transfusions & rehydration 2. **Prevention:** routine health management, nutrition, antibiotics & vaccination 3. **Curative:** gene therapies & stem cell transplantation 4. **Counselling:** education, support, familial implications & genetic testing