Structural Defects

Structural defects

95% of structural variants are caused by single amino acid replacement .This amino acid replacement or substitution changes the quality or characrtistics of haemoglobin. For example HbS, C, E, D, G, O all contain substitution of a different amino acid into the normal amino acid sequence of beta globin chain.

Sickle cell disease

Hemoglobin S

HbS substitution of Glutamic Acid at position 6 of the beta globin gene leading to the production of a defective form of hemoglobin S. HbS has a tendency to polymerize and deform the red blood cells into characteristic sickle cell.

Prevalence: Effects million throughout the world. Common in sub-Saharan Africa, Cuba, South America, Central America, Saudi Arabia, India, Mediterranean.

• Homozygous sickle cell: HbSS
• Heterozygous sickle cell: HbSA
• Compound Heterozygous: HbSE, HbSE, HbD Punjab, HbS O Arab, HbS/HPFH, HbS/Beta Thal, HbS/alpha Thal.

Sickle Cell Disease Haplotypes

• Senegal
• Benin
• Bantu
• Asian

Pathophysiology

Deoxygenation of HbS leads to the conformational changes triggers the formation of large polymers that distorts red blood cells into a sickle shape and decreases the elasticity.

• complex chronic inflammatory condition.
• State of chronic activation of coagulation system.
• Red cell membrane abnormalities.
• Nitric oxide depletion
• Increase whole blood viscosity

Clinical Manifestations Sickle Cell Disease

• Anemia
• Crisis
• complications

Acute complications

• Aplastic crisis
• Acute chest syndrome
• Acute splenic sequestration
• Acute painful crisis
• Priapism
• Stroke
• Recurrent Vasoclusive crisis
• Papillary necrosis
• Sepsis

Chronic complications

• Anemia
• Jaundice
• Splenomegaly
• Cardiomegaly
• Cholithisais
• Delayed growth
• Pulmonary hypertension
• Leg ulcers
• Retinopathy
• Avascular necrosis
• Transfusion Hemosiderosis

Sickle Cell Disease Types of Crisies

• Hemolytic crisis
• Aplastic crisis
• Sequestration crisis
• Vasoclusive crises

Sickle Cell Disease Diagnostic Tools & Treatment

Diagnostic Tools

• Peripheral blood finding.
• Sickling test
• Haemoglobin electrophoresis.
• ESR .
• Unconjugated bilirubin.
• LDH & haptoglobin.
• Newly born screening.
• Prenatal diagnosis.

Sickle Cell Disease Treatment

• Daily preventive measures.
• Routine health care .
• Infections.
• Transfusion therapy.
• Pain management.
• New therapeutic modalities.
• Hydroxyurea
• Bone marrow transplantation.
• Psychosocial issues.
• Gene therapy.