Sickle Cell Anemia

Sickle Cell Disease Overview

• Sickle cell disease is a genetic condition affecting red blood cells.
• Red blood cells in individuals with sickle cell disease contain abnormal haemoglobin.
• This abnormal haemoglobin results in distorted red blood cell shapes (sickle cells).
• Walter Noel's blood smear (December 31, 1904) marked the first observation of sickle cells.
• Sickle cells have a crescent shape instead of the usual disc shape.
• These abnormal shapes can cause problems with blood flow.

Pathophysiology of Sickle Cell Disease (SCD)

• Molecular Pathology: A single nucleotide mutation (GAG to GUG) occurs in the beta-globin gene (the 6th codon), resulting in the substitution of glutamic acid with valine.

• Biochemical Pathology: The mutation alters the haemoglobin protein structure. This abnormal haemoglobin (HbS) polymerizes (sticks together) when deoxygenated.

• Cellular Pathology: Deoxygenated HbS causes sickle-shaped red blood cells (RBCs). These rigid, misshapen cells impede blood flow.

• Vascular Pathology: Sickled RBCs block small blood vessels, leading to vaso-occlusion (blockage).

Consequences of HbS Polymerization and RBC Sickling

• Red cell injury: Damage to red blood cells from sickling.

• Hemolysis: Destruction of red blood cells.

• RBC dehydration and dense cell formation: Dehydrated red blood cells become clumpier.

• Adhesion of RBCs to venule endothelium: Sickled cells stick to the lining of blood vessels.

• Formation of heterocellular aggregates (WBC, SC): Inflammatory cells and red blood cells clump together.

• Vasooclusion: Blood clots block blood vessels.

• Local hypoxia (low oxygen): Reduced blood flow causes oxygen deficiency

• Propagation of vasooclusion in adjacent vasculature: Blockages spread to nearby blood vessels.

Molecular Pathology of SCD

• Normal versus sickle beta-globin structures are compared: a single amino acid change occurs at the 6th codon within the beta-globin protein

• Normal haemoglobin (HbA) contains glutamic acid

  • Sickle haemoglobin (HbS) contains valine

Hemoglobin Genes and Products (in SCD)

• Different types of haemoglobin exist;
• Hb F (2-20%)
• Hb A2 (3%)
• Hb S (80-95%)
• These haemoglobins are seen during various stages of life, and exist in different proportions (percentages).

Clinical Pathology of SCD

• Anemia: Chronic intravascular haemolytic anemia, acute episodes of severe anemia, acute splenic sequestration, acute hemolysis ("hyperhemolysis").
• Vasooclusion: Microvascular (clinically silent), Macrovascular occlusion causes ischemic/infarctive damage (pain episodes, stroke, acute chest syndrome, renal papillary necrosis, splenic infarction).
• Chronic organ damage: Splenic dysfunction (high risk of bacterial infection), Chronic vascular occlusion affects lungs, kidneys, gallbladder, eyes, joints, heart.

Laboratory Findings in SCD

• Low haemoglobin (Hb) levels (6-9g/dL).
• Sickled red blood cells.
• Target cells.
• Splenic atrophy.
• Positive screening test for sickling (blood is often deoxygenated using Sodium Phosphate, Na2HPO4). Hb electrophoresis shows HbS.

Managing Sickle Cell Disease

• Fluids
• Antibiotics
• Rest
• Pain medication
• Prevention of infections
• Healthy lifestyle.