The first reports dating from 1995 showed that taking hydroxycarbamide regularly reduced the frequency of painful crises and of the acute chest syndrome and also reduced the need for blood transfusion. This breakthrough has since been followed by numerous reports from around the world demonstrating unequivocally that treatment with hydroxycarbamide fundamentally changes the natural history of sickle cell disease for the better.
As well as having beneficial effects on the most feared acute complications of sickle cell disease, such as the acute chest syndrome, hydroxycarbamide also prevents many of the chronic complications of the disease. It restores low oxygen levels improving the functioning of the lungs, it reduces protein loss in the urine preventing kidney failure, it reduces the chance of chronic liver disease and it reduces the risk of stroke. Perhaps most importantly of all, taken regularly in the long term, it also has a profound effect on survival; in one study it reduced the risk of death during the study period by 40% and in another study increased the probability of survival at 10 years follow up to 86%, in the treated group, compared with 68% in the patients who did not take hydroxycarbamide.
A recent report in the British Journal of Haematology, from a group of researchers in Memphis, Tennessee, has added another important piece information to our knowledge about the beneficial effects of hydroxycarbamide in sickle cell disease. The researchers looked at the damaging effects of sickle cell disease on the brain. The most obvious complication of sickle cell is a stroke, which can result in paralysis, seizures and loss of speech, and is a devastating complication which, without any intervention, will occur in 24% of individuals by the age of 45 years. Screening for early signs of an increased risk of stroke in children by transcranial doppler and prompt blood transfusion have greatly reduced the risk of this complication.
But sickle cell also has more subtle detrimental effects on brain structure and function. Over time so-called “silent cerebral infarcts” or SCI’s appear in the white matter of the brain. These SCI’s gradually increase in frequency and by 18 years of age are found in 39% of individuals. For many years they were not thought to be harmful but we now know, on the contrary, that SCI’s are associated with a significant decrease in IQ, learning difficulties and poor performance in neuropsychological tests, with overall negative effects on educational attainment and employment prospects.
The study from Memphis looked at 50 children with sickle cell anaemia who were all taking hydroxycarbamide long term. Effects on the brain were evaluated by detailed brain scans after 3 years and again after 6 years of treatment. Normally, it would be expected that the number of children in whom SCI’s were found would increase progressively over this six year period but, in these children, all taking hydroxycarbamide, the number of SCI’s remained unchanged and stable. The implication is therefore that treatment with hydroxycarbamide will prevent the development of SCI’s and the serious neuropsychological sequelae associated with them.
This is an important study. Not only does it emphasis yet again the value of hydroxycarbamide, but for the first time it demonstrates that there is a practicable alternative to blood transfusion to prevent this insidious complication of sickle cell, affecting large numbers of individuals with the disease.
Hydroxycarbamide treatment and brain MRI/MRA findings in children with sickle cell anaemia. Kerri Nottage, Russell Ware, Banu Aygun, Matthew Smeltzer, Guolian Kang, Joseph Moen, Winifred Wang, Jane Hankins and Kathleen Helton. British Journal of Haematology (2016), volume 175, pages 331-338
Other blogs of interest
The TWITCH trial – a major improvement in the care of children at risk of stroke (18/02/16)
More on hydroxycarbamide (07/01/15)