ABSTRACT
Sickle cell disease is an autosomal dominant haemoglobinopathy found in Negroes, in non-Negroes from around the Mediterranean, and in parts of India. The β chain of haemoglobin A (HbA) has valine substituted for glutamine in position 6 to produce HbS. In the heterozygous form (sickle cell trait) this provides some protection against falciparum malaria. Ten per cent of Negroes in the UK have sickle cell trait. This is associated with a normal life expectancy, an Hb greater than 11g dl−1, no clinical signs or symptoms and sickling only if the SaO2 is less than 40%. There is, however, an increased risk of pulmonary infarcts. Co-dominant expression of the haemoglobin gene allows normal and abnormal haemoglobin to coexist. Haemoglobin S may be produced with mutant haemoglobins such as haemoglobin C (giving SC disease), and with β thalassaemia. In the homozygote, deoxygenated HbS becomes insoluble and causes red blood cells to become rigid and sickle shaped. This is more likely if hypoxia, acidosis, low temperature or cellular dehydration occurs. Sickling is initially reversible, but when potassium and water are lost from the cell it becomes irreversible. Sickled cells result in decreased microvascular blood flow, causing further local hypoxia, acidosis and thus more sickling. Local infarction causes the symptoms and signs of a sickle cell crisis. Chest symptoms (pleuritic pain, cough and fever), musculoskeletal complaints (bone pain, muscle tenderness, erythema), abdominal pain, splenic sequestration (acute anaemia and aplastic crisis), haematuria, priapism and cerebrovascular events (transient ischaemic attacks (TIAs) and strokes) may occur during a crisis. Chronic haemolytic anaemia, increased infection risk and specific organ damage such as ‘autosplenectomy’, gallstones, renal and pulmonary damage occur as the result of long-term sickling. Osteomyelitis and meningitis are more common and prophylactic antibiotics are often given. Homozygotes usually present in early childhood when HbF levels fall and HbS predominates. Survival beyond the fourth or fifth decade is rare.
