Sickle Cell Anaemia, Thalassemia, Neonatal Physiological And Haemolytic Jaundice Case Studies

Sickle Cell Anaemia

Case 1: Extremities And Jaundice

A 10 years old girl child was brought to the emergency department with severe pain in her extremities and jaundice. She had a history of repeated blood transfusions. On examination, she had pallor and icterus. Laboratory investigations showed Hb– 7 gm% and a single band of HbS in Hb electrophoresis.

• Diagnosis – Sickle cell anaemia.
• Confirmatory test – Hb electrophoresis.

Read And Learn More: Biochemistry Clinical Case Studies With Answers

Sickle Cell Anaemia

1. Autosomal recessive disorder.
2. It is an example of a partially acceptable missense point mutation.
3. Glutamate is replaced by valine at the 6th position of the beta chain.
4. This substitution causes localized stickiness on the surface of deoxy- HbS.
5. This change causes the polymerization of HbS under deoxygenated state and the formation of fibre which distorts the shape of RBCs into a sickle shape
6. These distorted RBCs occlude the microvasculature and cause intense pain in the affected areas.
7. Rapid destruction of RBCs causes jaundice (haemolytic).

Sickle Cell Anaemia Clinical Symptoms

Pain, fatigue, frequent infections, breathlessness, jaundice, anaemia, painful swelling of hands and feet etc.

Sickle Cell Anaemia Complications/Crisis

• Acute chest syndrome– due to blockade of vessels in the lung.
• Splenic sequestration– spleen enlarged and painful.
• Pain crisis– due to blockade of microvasculature.
• Stroke, priapism etc.

Sickle Cell Anaemia Treatment

• Medication– antibiotic for infection, hydroxyurea, folic acid and analgesics.
• Blood transfusion.
• Bone marrow transplantation.

Case 2: Acute Breathlessness

A 15 years old apparently normal boy went on mountaineering. He developed acute breathlessness and found to be slightly anaemic upon examination. Laboratory investigation showed AS pattern.

1. Name the clinical condition.
   • Sickle cell trait.
2. Name the laboratory tests done for its diagnosis.
   • Hb electrophoresis– on Hb electrophoresis, we get two bands, one of HbA and the other is HbS.
   • When subjected to electrophoresis in an alkaline medium (pH 8.6), sickle-cell haemoglobin (HbS) moves more slowly towards the anode (positive electrode) than does adult haemoglobin (HbA).
   • The slow mobility of HbS is due to less negative charge, caused by the absence of glutamate residues that carry a negative charge.
3. Mention the molecular defect involved.
4. Explain the biochemical changes seen in this condition.

Thalassemia

Case 1: Hepatosplenomegaly

The one-year-old girl child was brought to the emergency department with hepatosplenomegaly. She had a history of repeated blood transfusions. On examination, she has pallor and icterus. Laboratory investigations showed Hb– 7 gm% and the X-ray skull shows a ‘hair on end appearance’.

• Diagnosis– Thalassemia major.
• Thalassemia is due to a decrease in the synthesis of normal hemoglobin.
• Confirmatory Test– Hb electrophoresis.

Thalassemia Types

Alpha thalassemia– decrease synthesis or total absence of α-globin chain, 4 types.

Beta thalassemia- decreased synthesis or total absence of β-globin chain, 2 types:

1. β – thalassemia major- defect in both genes (homozygous).
2. β – thalassemia minor- defect in a single gene (heterozygous).

Beta thalassemia Clinical Symptoms

1. Fatigue, weakness, anemia, failure to thrive, jaundice, breathlessness, hepatosplenomegaly, etc.
2. X-ray skull shows ‘hair on end appearance’ due to marrow expansion.

Beta thalassemia Treatment

1. Supportive care.
2. Frequent blood transfusion.
3. Iron chelating agents.
4. Stem cell transplant.

Neonatal Physiological Jaundice

Case 1: Indirect Bilirubin

A 28-year-old mother delivered a premature baby in the 34th week of gestation. The baby cried well after the birth, and all reflexes were normal. But three days after birth, the mother observed the yellow skin and eyes of the baby. On blood examination, the indirect bilirubin level was found to be 10 mg/dl.

Question 1. What is the most probable diagnosis?
Answer:

Probable diagnosis:

• Physiological jaundice.
• It is due to the inability of the liver enzyme system to conjugate bilirubin. It mostly occurs in premature babies in which UDP-glucuronyl-transferase enzyme activity is low because of immature hepatocytes.

Question 2. What is the most appropriate treatment modality for this condition?
Answer:

Treatment modality:

• Phototherapy.
• Bilirubin absorbs blue light (420–470 nm) and gets converted into non-toxic photo-isomer lumirubin. Lumirubin can be excreted by the kidneys in an unconjugated form.

Question 3. What is the role of phenobarbital in unconjugated hyperbilirubinemia?
Answer: It induces a hepatic enzyme system for the uptake, conjugation, and secretion of bilirubin.

Question 4. What is kernicterus?
Answer:

kernicterus:

It is the deposition of bilirubin in brain tissue causing seizures, encephalitis, and mental retardation. In infants, the blood-brain barrier is not matured. Hence bilirubin can easily enter
the brain.

Case 2: A Four-Day-Old Neonate With Jaundice

• A four-day-old neonate was admitted to the hospital with jaundice. His mother was 25 years old and this was her first pregnancy. The child was born by Full term normal delivery at 38 weeks of gestation; weight was 3 kg having no apparent complications.
• On 4th day after birth, the mother noticed yellowish discoloration of the sclera. On laboratory investigation serum total bilirubin was 21 mg/dl and indirect was 18.2 mg/dl. There was no blood group incompatibility. Phototherapy was started and the bilirubin level showed a decreasing trend after 12, 24, and 48 hrs.

Question 1. Why phototherapy causes a decrease in the bilirubin level?
Answer:

Question 2. What is δ-bilirubin?
Answer:

It is conjugated bilirubin covalently bound to albumin. Because of covalent binding, this bilirubin has a longer half-life in plasma than conventional conjugated bilirubin. It remains elevated during the recovery phase of obstructive jaundice and patients continue to appear jaundiced after conjugated bilirubin levels have returned to normal.

Haemolytic Jaundice

Case 1: Acute Haemolytic Crisis

A 25 years old man on treatment with anti-malarial drugs developed an acute haemolytic crisis indicated by decreased Hb%, increased serum bilirubin and no bile pigments in urine.

1. Name the defect and enzyme.

Glucose-6-phosphate dehydrogenase deficiency. As such asymptomatic but when exposed to oxidant drugs (Primaquine, sulfamethoxazole and acetanilide) or severe infection produces haemolysis due to free radical generation.

2. Explain the biochemical basis of the development of haemolytic disease.

HMP shunt is the only pathway to produce NADPH in erythrocytes. Decreased activity of glucose-6-phosphate dehydrogenase leads to the decreased synthesis of NADPH. This causes the accumulation of methemoglobin and peroxides in erythrocytes leading to haemolysis.

Case 2: Malaria

A 38 years old person suffering from fever and chills was diagnosed as a malaria patient. He was given the antimalarial drug Primaquine. After a few days, he complained of passing red-coloured urine and weakness. Laboratory data showed Hb level 7.5 gm% and unconjugated bilirubin 7.8 mg/dl.

Question 1. Why rise in unconjugated bilirubin?
Answer:

Due to haemolysis, rapid destruction of RBCs occurs. Heme releases into the circulation and an increase in unconjugated bilirubin occurs.

Question 2. Explain the mechanism of anaemia.
Answer:

• NADPH is required for the regeneration of reduced glutathione, which helps in the maintenance of RBC membrane integrity. It is also required for keeping iron in a reduced state hence preventing methemoglobin formation.
• Rapid haemolysis of RBCs in the absence of NADPH due to G6PD deficiency occurs, resulting in anaemia.

Case 3: Acute Haemolytic Crisis

A 25 years old man on treatment with antimalarial drugs, developed an acute haemolytic crisis indicated by decreased Hb%, increased serum bilirubin and no bile pigment in urine.

Types of Jaundice

• SGOT– Serum Glutamate Oxaloacetate Transaminase.
• SGPT– Serum Glutamate Pyruvate Transaminase.
• ALP– Alkaline Phosphatase.
• 5’-NT– 5’-Nucleotidase.
• GGT– Gamma Glutamyl transferase