Sickle cell anemia

• Sickle cell anemia is a genetic disorder caused by a mutation in the HBB gene, which encodes the beta-globin subunit of hemoglobin.

• This mutation leads to the production of abnormal hemoglobin known as hemoglobin S (HbS).

• Under low oxygen conditions, HbS can polymerize, causing RBCs to become rigid and sickle shaped.

• These misshapen cells can block blood flow and break down prematurely, leading to anemia and other complications.

Pathophysiology of Sickle cell anemia

• The mutation in the HBB gene results in the substitution of valine for glutamic acid at the sixth position of the beta-globin chain.

• This single amino acid change causes HbS to polymerize when deoxygenated, distorting the RBCs into a sickle shape.

• These sickle cells are less flexible and can block small blood vessels, leading to tissue ischemia and pain.

• They also have a shorter lifespan (10-20 days) compared to normal RBCs (about 120 days), leading to chronic hemolytic anemia.

Symptoms

Symptoms of sickle cell anemia vary in severity and can include:

1. Anemia: Fatigue, pallor, and shortness of breath due to chronic hemolysis.

2. Pain Crises (Vaso-occlusive Crises): Severe pain episodes due to blockage of blood flow in small blood vessels.

3. Swelling: Hands and feet swelling (dactylitis) in infants and young children.

4. Frequent Infections: Increased susceptibility to infections due to spleen dysfunction.

5. Delayed Growth and Puberty: In children and adolescents.

6. Jaundice: Yellowing of the skin and eyes due to hemolysis.

7. Complications: Stroke, acute chest syndrome, pulmonary hypertension, organ damage, and leg ulcers.

Diagnosis

Sickle cell anemia is diagnosed through:

1. Hemoglobin Electrophoresis: Identifies the presence of HbS.

2. Blood Smear: Shows characteristic sickle-shaped RBCs.

3. Newborn Screening: Routinely performed in many countries.

4. Genetic Testing: Confirms mutations in the HBB gene.

Treatment

Treatment focuses on managing symptoms, preventing complications, and addressing underlying causes:

1. Pain Management: Analgesics, hydration, and sometimes opioids for severe pain crises.

2. Hydroxyurea: Increases fetal hemoglobin (HbF) levels, reducing the frequency of pain crises and other complications.

3. Blood Transfusions: Used to treat severe anemia and prevent complications like stroke.

4. Bone Marrow Transplant: Potential cure but associated with significant risks and is not suitable for all patients.

5. Preventive Measures: Vaccinations, prophylactic antibiotics, and regular health check-ups.

6. Gene Therapy: Emerging treatment with potential for curing the disease.