Determinants of severity in sickle cell disease

Sickle cell disease is a very variable condition, with outcomes ranging from death in childhood to living relatively symptom free into the 8th decade. Much of this variability is unexplained. The co-inheritance of alpha thalassaemia and factors determining HbF levels significantly modify the phenotype, but few other significant genetic variants have been identified, despite extensive studies. Environmental factors are undoubtedly important, with socioeconomics and access to basic medical care explaining the huge differences in outcomes between many lowand high-income countries. Exposure to cold and windy weather seems to precipitate acute complications in many people, although these effects are unpredictable and vary with geography. Many studies have tried to identify prognostic factors which can be used to predict outcomes, particularly when applied in infancy. Overall, low haemoglobin, low haemoglobin F percentage and high reticulocytes in childhood are associated with worse outcomes, although again these effects are fairly weak and inconsistent.