Single amino acid substitution on B-chain at position 6 of valine for glutamic acid

• Autosomal co-dominant: homozygotes have 90-100% HbS, heterozygotes have 20-40% 

• Normochromic
• Microcytic anaemia
• Sickled cells
• Reticulocytosis
• Features of splenic atrophy (target cells, acanthocytes, Howell-Jolly bodies)

• Haemolytic anaemia results in cardiac failure
• Pigment gallstones
• Thrombosis and infarction - abdomen, chest, splene, bone
• Infection - salmonella osteomyelitis, pneumococcal sepsis

Defective globin chain synthesis - causes abnormal haemoglobin production

• Alpha Thalassaemia - China, Asia, Africa
• Beta Thalassaemia - Mediterranean, Middle East

• Hypochromic microcytic anaemia
• Reticulocytosis
• Target cells
• Nucleated red cells
• Increased haemoglobin F

• Marrow hyperplasia
• Iron overload (cirrhosis, endocrine disturbance, pancreatitis)
• Hypersplenism - decreased red cell survival time, leucopaenia, thrombocytopenia