4 The clinical features of sickle cell disease

Abstract

Evidence from structural studies of DNA suggest that the sickle cell mutation has arisen on at least three separate occasions in Africa and as a fourth independent mutation in the Eastern Province of Saudi Arabia or India. The pathophysiology of sickle cell disease is essentially similar in these different areas although the frequency and severity of complications may vary between areas. Generally, the chronic haemolysis and resulting anaemia is well tolerated, although serious morbidity and occasionally mortality may be associated with the aplastic crisis or cholelithiasis. Exacerbation of anaemia below steady state levels occurs with chronic glomerular damage and renal failure, especially in older patients. Most of the morbidity of the disease arises from bone marrow necrosis in the painful crisis or from vaso-occlusive manifestations. Changes in the splenic circulation result in life-threatening episodes of acute splenic sequestration, the chronic morbidity of hypersplenism, and splenic dysfunction renders children prone to pneumococcal septicaemia. Chronic organ damage contributes to chronic leg ulceration in adolescence and progressive renal, pulmonary, and occasionally cardiovascular impairment in later life. The clinical spectrum of homozygous sickle cell disease varies widely between patients. Factors contributing to this variability include alpha-thalassaemia, persistence of high HbF levels, haematology, social circumstances, and geographical and climatic variation. Many of the causes of mortality may be prevented or more effectively treated, leading to increased survival and an increased quality of life in affected subjects.