HAEM

BETA THALASSAEMIA MAJOR

A 4-year-old girl is referred by the GP to the haematology clinic because of pallor. On
examination, she is pale with a tinge of jaundice. Her liver and spleen are enlarged. The
Haematologist ordered further investigations and a final diagnosis of beta thalassaemia major
is made.
a. Based on the diagnosis of beta thalassemia major, explain the reason for the patient’s
pallor and jaundice. (4)
Beta thalassemia major is due to defective beta globin gene of haemoglobin, which results in
decreased synthesis/production of beta globin. This results in increased haemolysis of RBC,
which leads to anaemia (pallor) and jaundice (haemolytic jaundice).
b. Explain the pathophysiological basis of the liver and splenic enlargement (4)
Hepatosplenomegaly in individuals with beta thalassemia may occur due to increased
destruction of red blood cells, the formation of blood cells outside of the bone marrow
(extramedullary haematopoiesis) due to ineffective erythropoiesis, repeated blood
transfusions, or iron overload.
c. List two investigations which can be used to confirm the final diagnosis of beta-
thalassemia major in this patient. (2)
Since the synthesis of beta globin is reduced in beta thalassemia, the body compensates by
increasing the synthesis of delta globin (thus increase in HbA2) and gamma globin (thus
increase in HbF) and these can be detected in the blood using haemoglobin electrophoresis
and High Performance Liquid Chromatography (HPLC) to confirm the diagnosis of beta
thalassaemia.
2. A 6-year-old boy with a history of beta-thalassaemia major, was found to be pale. His
haemoglobin was very low. He was transfused with 2 units of packed cells.
What are the molecular defects in beta-thalassaemia? (4 marks)
Reduced or absent beta-chain production while synthesis of the a-chain is normal and hence
there is an imbalanced globin-chain synthesis with the production of excess alpha-chain.
Describe the pathogenesis involved in beta-thalassemia. (2 marks)
Diminished survival of red cells and their precursors, which results from the imbalance in α-
and β-globin synthesis. Unpaired α chains precipitate within red cell precursors cause cell
membrane damage.
Explain the reason for grouping and matching of the donor and recipient blood necessary
prior to transfusion. (1 mark)
This is to prevent immune reaction between the recipient’s and donor’s blood. This involves
the antigen presented on red blood cells and antibody presented in the blood
To ensure the donor’s antibody does not react to the recipient’s antigen and vice versa.
If the child is blood group A positive, name the blood group/groups which can be given to
him and explain the reason. (1+2=3 marks)
Blood group/groups- Rh(+)ve A or O.
Explanation-Because these do not contain anti-A to react to the child’s red cells which
contain antigen (agglutinogen A) on the surface.

A man has Beta thalassemia major and is currently coming for a follow up and blood
transfusion.
A. List down the three functions of ATP in embden mayerhof parnas pathway (Hexose
monophospate pathway/glycolysis) (3m)
B. What are the types of hemoglobin and their chains that can be found in normal adults?
(3m)
C. What is the molecular defect of beta thalassemia? (2m)
D. Explain how thalassemia can cause hydrops fetalis. (2m)
IRON DEFICIENCY ANEMIA
A 19 year old woman presents with a history of menorrhagia for the last three months.
Physical examination revealed pallor. She was diagnosed with iron deficiency anaemia and
iron therapy was started.

a. Describe the functional and storage pools of the deficient micronutrient in this patient
About 80% of functional iron is in haemoglobin, myoglobin and iron containing enzymes
(catalase, cytochromes). The remaining 15-20% is stored as haemosiderin (Macrophages in
bone marrow, liver & Spleen) & ferritin (Liver, spleen, bone marrow & skeletal muscles).
(2 marks)

b. Describe the pathogenesis of anaemia in this patient

 Anaemia appears when iron stores are completely depleted
 There is impaired haemoglobin synthesis
 The survival of erythroid precursors and erythrocytes is reduced.
 This results in hypochromic microcytic anaemia
(4 marks)

c. List TWO (2) causes of iron deficiency anaemia

Answer : (Any TWO)
i. Dietary lack of iron
ii. Impaired iron absorption
iii. Increased requirement of iron
iv. Chronic blood loss
(2 marks)
 d. State TWO (2) laboratory tests for the confirmation of anaemia in this patient. (2
Marks)
Answer : (Any TWO)
i. Serum iron
ii. Serum ferritin
iii. Total plasma iron binding capacity (TiBC)
ACUTE HAEMOLYTIC REACTION
A 29 year old woman underwent a caesarean section to deliver a baby. Due to heavy blood
loss, a unit of blood was started on an intravenous (IV) line. Within minutes, she developed
fever with chills, restlessness and vomiting

a. What is the most likely reaction in this patient?

Acute haemolytic reaction (1 mark)

b. State FOUR (4) steps to be taken in the immediate management of this reaction
i. Infusion must be stopped
ii. Blood sample taken from the patient for testing
iii. Urine sample for presence of haemoglobin
iv. Notification to the blood bank or transfusion service (4 marks)

c. List THREE (3) laboratory tests that will be required to confirm the diagnosis
i. Repetition of ABO blood group type on pretransfusion and post-transfusion blood
sample
ii. Direct antiglobulin test (DAT)/Coomb’s test
iii. Repetition of cross matching
iv. Plasma free haemoflobin
v. Serum haptoglobin
vi. Serum bilirubin
vii. Serum Lactate dehydrogenase levels
viii. Haemoglobinuria (3 marks)
 d. State TWO (2) complications which can arise in this patient
Answer : (any two)
a. Hypotension
b. Renal failure
c. Disseminated intravascular coagulation (DIC)

ACUTE LYMPHOBLASTIC ANEMIA

A 5-year-old boy is brought to the paediatrician by his mother with complaints of tiredness
and fatigue for the last 2 months. On examination, pallor and generalised cervical
lymphadenopathy are noted. A complete blood count shows evidence of anaemia,
neutropenia and thrombocytopenia. A peripheral blood smear shows the presence of
numerous lymphoblasts and a provisional diagnosis of acute lymphoblastic leukaemia is
made. Rituximab is prescribed.
3A. Describe the microscopic differences between the primary and secondary follicles of a
lymph node. (2 marks)
Primary follicles have no germinal centres and appear as uniform dark stained areas.
Secondary follicles have pale stained germinal centres surrounded by dark stained areas.
3B. Describe the morphology of the abnormal cells seen in the peripheral blood of this
patient. (3 marks)
Lymphoblasts are small to medium-sized cells with high nucleus-to-cytoplasmic ratios, fine
chromatin, inconspicuous nucleoli and agranular cytoplasm.
3C. List TWO other laboratory investigations to confirm the diagnosis in this patient. (2
marks)
Bone marrow aspiration/biopsy
Immunophenotyping
Cytogenic analysis
Lymph node biopsy
3D. Explain the mechanism of action of the drug prescribed and its benefit compared to
conventional anticancer agents.
Answer:
Mechanism: Monoclonal antibodies bind to specific target protein (CD20 in this case) on
cancer cells (B cell in this case) and cancer cells are killed by complement mediated lysis
Benefit: highly targeted therapy with lesser adverse effects
DENGUE
2. A 24-year-old university student was admitted to the hospital with a 4-day history of
high fever, headache, vomiting and malaise, and a 2-day history of epistaxis and
haemetemesis. The patient lived in an area that was endemic for dengue and reported
a previous history of dengue fever. A provisional diagnosis of dengue haemorrhagic
fever was made, and blood tests and further investigations were carried out.
a. Name the family which the dengue virus belongs to and state both the vectors
involved in the transmission of dengue. [2]
Family: Flaviviridae
Vectors: Aedes aegypti and Aedes albopictus
b. Explain why the patient developed dengue haemorrhagic fever despite being infected
with the dengue virus in the past. [3]
 After an earlier attack of dengue, antibodies are formed that are specific for that
serotype.
 On subsequent infection with a different serotype, the antibodies bind to the virus and
not only fail to neutralize it but actually enhance its ability to infect monocytes.
 Infection of increased numbers of monocytes results in an increased release of
cytokines into the circulation that leads to vascular damage, shock and haemorrhage.
c. State TWO (2) investigations to confirm the diagnosis of dengue haemorrhagic fever in
this patient. [2]
 NS1 (non-structural protein)
 Serological detection of dengue IgG/IgM antibodies
 Antigen detection using PCR
 Antigen detection using ELISA
d. State THREE (3) characteristics that make the mosquito an effective and efficient vector
for dengue. [3]
 Highly domesticated
 Highly anthropophagic
 Cryptic breeding
 Multiple biter
 Transovarial transmission
 Highly resistant egg to desiccation
 Smart breeder- skip oviposition