Sickle-cell disease.
Sickle-cell disease is one of the most common severe monogenic disorders in the world. Haemoglobin polymerisation, leading to erythrocyte rigidity and vaso-occlusion, is central to the pathophysiology of this disease, although the importance of chronic anaemia, haemolysis, and vasculopathy has been established. Clinical management is basic and few treatments have a robust evidence base. One of the main problems of sickle-cell disease in children is the development of cerebrovascular disease and cognitive impairment, and the role of blood transfusion and hydroxycarbamide for prevention of these complications is starting to be understood. Recurrent episodes of vaso-occlusion and inflammation result in progressive damage to most organs, including the brain, kidneys, lungs, bones, and cardiovascular system, which becomes apparent with increasing age. Most people with sickle-cell disease live in Africa, where little is known about this disease; however, we do know that the disorder follows a more severe clinical course in Africa than for the rest of the world and that infectious diseases have a role in causing this increased severity of sickle-cell disease. More work is needed to develop effective treatments that specifically target pathophysiological changes and clinical complications of sickle-cell disease.
Department of Paediatric Haematology, King's College Hospital NHS Foundation Trust, King's College London, London, UK. david.rees@kcl.ac.uk
David C
DC
Rees
Thomas N
TN
Williams
Mark T
MT
Gladwin
D056586:Acute Chest Syndrome / Q000209:etiology / Q000628:therapy; D000349:Africa; D000755:Anemia, Sickle Cell / Q000097:blood / Q000145:classification / Q000150:complications / Q000175:diagnosis / Q000453:epidemiology / Q000628:therapy; D000986:Antisickling Agents / Q000627:therapeutic use; D001803:Blood Transfusion; D004198:Disease Susceptibility; D004912:Erythrocytes / Q000473:pathology*; D018014:Gene Transfer Techniques; D006239:Haplotypes; D006331:Heart Diseases / Q000209:etiology / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells; D006461:Hemolysis; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000628:therapy; D007502:Iron Chelating Agents / Q000627:therapeutic use; D007674:Kidney Diseases / Q000209:etiology / Q000628:therapy; D008403:Mass Screening; D009422:Nervous System Diseases / Q000209:etiology / Q000628:therapy; D010146:Pain / Q000209:etiology; D059408:Pain Management; D058105:Polymerization; D012720:Severity of Illness Index
D000986:Antisickling Agents; D007502:Iron Chelating Agents; D006918:Hydroxyurea