[Pathophysiology and treatment of sickle-cell disease].
Sickle-cell disease is a hereditary haemoglobinopathy caused by a mutation in the beta-globin gene. The disease is characterised by recurrent vaso-occlusive crises resulting in severe organ damage and a sharply reduced life expectancy. The formation of haemoglobin-S polymers in hypoxic conditions plays a pivotal role in sickle-cell disease and produces the characteristic phenotype of sickle-shaped erythrocytes that promote vasoocclusion. Endothelial cell activation, enhanced erythrocyte and leukocyte adhesion, vasoconstriction and coagulation activation play an important role in vaso-occlusive crises. Treatment of pain and hydration remain the main interventions in the management ofvaso-occlusive crises. Hydroxyurea has been shown to prevent vaso-occlusive crises by increasing the amount of foetal haemoglobin. Allogeneic stem-cell transplantation is the only curative therapy. However, transplantation-related mortality, graft-versus-host disease and the limited availability of HLA-identical donors restrict this therapeutic option.
van Beers
E J
EJ
Afd. Hematologie, Academisch Medisch Centrum/Universiteit van Amsterdam, Postbus 22.660, 1100 DD Amsterdam.
Peters
M
M
Biemond
B J
BJ
D000755:Anemia, Sickle Cell / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D000986:Antisickling Agents / Q000627:therapeutic use; D002448:Cell Adhesion; D003131:Combined Modality Therapy; D004912:Erythrocytes / Q000473:pathology*; D006801:Humans; D006918:Hydroxyurea / Q000627:therapeutic use; D033581:Stem Cell Transplantation
D000986:Antisickling Agents; D006918:Hydroxyurea