Sickle Cell Anemia

Sickle Cell Anemia Introduction

• 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 polymerizes, causing red blood cells (RBCs) to become rigid and sickle-shaped.
• These misshapen cells can block blood flow and break down prematurely, leading to anemia and various complications.

Pathophysiology

• Genetic Mutation: Substitution of valine for glutamic acid at the sixth position of the beta-globin chain.
• Sickling of RBCs: Deoxygenated HbS causes RBCs to become rigid and sickle-shaped.
• Vaso-occlusion: Rigid cells block small blood vessels, leading to tissue ischemia and pain.
• Hemolysis: Sickle cells have a shorter lifespan (10–20 days) compared to normal RBCs (about 120 days), causing chronic hemolytic anemia.

Symptoms

1. Anemia: Fatigue, pallor, and shortness of breath due to chronic hemolysis.
2. Pain Crises: Severe pain episodes from blocked blood flow in small vessels.
3. Swelling: Dactylitis (swelling of hands and feet) in infants and young children.
4. Frequent Infections: Increased susceptibility due to spleen dysfunction.
5. Delayed Growth: In children and adolescents.
6. Jaundice: Yellowing of the skin and eyes from hemolysis.
7. Complications: Stroke, acute chest syndrome, pulmonary hypertension, organ damage, 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

1. Pain Management: Analgesics, hydration, and opioids for severe pain crises.
2. Hydroxyurea: Increases fetal hemoglobin (HbF) levels, reducing complications.
3. Blood Transfusions: Treat severe anemia and prevent complications like stroke.
4. Bone Marrow Transplant: Potential cure but carries significant risks.
5. Preventive Measures: Vaccinations, prophylactic antibiotics, regular check-ups.
6. Gene Therapy: Emerging treatment with potential for a cure.

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