Hydroxurea treatment in sickle cell children

Abstract

Sickle cell anaemia, the most prevalent genetic disease in the black population, is characterised by the polymerisation of the abnormal haemoglobin S, which leads to vascular occlusion and severe painful crisis. Hydroxyurea is the fi rst drug that has been shown to reduce the clinical severity of sickle cell anaemia in adults. Several trials have been carried out in more than 400 children in the last decade, using different therapeutic schedules. Enrolment was based on clinical vasoocclusive severity and few studies included children with cerebrovascular events. Hydroxyurea enhanced fetal haemoglobin expression in almost all the children, despite a large interindividual variability. Hydroxyurea signifi cantly reduces the number of vasoocclusive crises, hospitalisations, the frequency of the acute chest syndrome and the rate of transfusion. Long-term tolerance to hydroxyurea is good. However, clinical response does not correlate consistently with the degree and with the time of increment in fetal haemoglobin, suggesting that hydroxyurea may mediate some of its clinical benefi ts through other mechanisms such as the reduction of sickle erythrocytes – endothelial cells adherence and of the vasoconstrictive stimulus.