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.