Standard sickle cell treatments slash stroke risk in children: Review
Researchers highlight need for expanding access in low-, middle-income nations
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Hydroxyurea, blood transfusions, and donor blood stem cell transplants can significantly lower the risk of stroke in children and adolescents with sickle cell anemia (SCA), the most common and severe form of sickle cell disease.
That’s according to a systematic review and meta-analysis of 40 studies that also highlighted the need for expanding access to these lifesaving treatments in low- and middle-income countries (LMICs), where most affected children reside.
The near elimination of strokes in children with SCA may be possible with standard primary and secondary stroke prevention strategies, researchers noted.
“For children living in LMIC who remain untreated, for secondary stroke prevention, we have a unique opportunity to prevent lifelong [illness] and mortality with low-dose hydroxyurea (10 mg/kg/day) for as little as $0.15 per day,” they added.
The review study, “Primary and Secondary Stroke Prophylaxis in Children with Sickle Cell Anemia: A Meta-Analysis,” was published in Blood Advances.
SCA is a genetic disorder marked by sickle-shaped red blood cells that are destroyed prematurely and block small blood vessels. People with SCA, particularly children, are also at a higher risk of stroke, as blood vessel blockage that occurs in the brain can prevent some regions from receiving enough oxygen and nutrients, causing damage.
“Over the last four decades, medical care for children with SCA has evolved from no treatment to now evidence-based strategies for primary and secondary stroke prevention,” the researchers wrote.
Possible outcomes between high-, middle-income countries compared
Researchers in the U.S. conducted a systematic review to compare the effectiveness of several interventions with no intervention for stroke prevention in children and adolescents (collectively called children) with SCA. They focused on chronic blood transfusion therapy (CBT), hydroxyurea (HU), donor-derived hematopoietic (blood) stem cell transplant (HSCT), and revascularization surgery (RVS).
CBT dilutes sickled cells in the bloodstream, while hydroxyurea is a medication that reduces red blood cell sickling. Donor-derived HSCT replenishes the patient with new, healthy red blood cells from a donor, who can or cannot be related to the patient. RVS is a surgical procedure designed to enhance blood flow to the brain.
All but RVS were examined both for preventing a first stroke (primary prevention) and preventing recurrent strokes in children with a prior stroke (secondary prevention), while RVS was evaluated as a secondary prevention strategy alone.
Forty studies, involving more than 2,000 children and published before January 2025, were included. The researchers also compared possible outcomes between high-income countries (HICs) and LMICs, where nearly 99% of children with SCA are born.
One study in children with abnormal transcranial Doppler (TCD) velocities — a marker of high stroke risk — but who received no treatment showed that the stroke rate was 10.7 per 100 person-years, which accounts for the total number of patients and the amount of time each spent in the study. For example, 100 person-years can refer to data gathered from 100 patients who were followed for a year.
In contrast, pooled data from five studies evaluating hydroxyurea for primary stroke prevention showed a pooled stroke rate of one per 100 person-years and a death rate of 1.1 per 100 person-years. Similarly, pooled results from five studies of CBTs also showed a stroke rate of one per 100 person-years, but a lower death rate, at 0.3.
“In LMICs, hydroxyurea lowers stroke risk in children with abnormal TCD velocities to rates comparable with transfusion,” the team wrote.
The researchers were unable to analyze outcomes of HSCT as a primary prevention strategy due to a lack of clarity in the studies.
Hydroxyurea ‘is a reasonable alternative compared to no therapy’
For children who had already suffered a stroke, the stroke recurrence rate without any treatment was 19.6 per 100 person-years, according to pooled data from three studies. In LIMCs, this rate rose to 36 to 51 per 100 person-years in the first year after initial stroke.
By contrast, children treated with hydroxyurea after a stroke had a significantly lower recurrence rate — 3.5 strokes per 100 person-years — based on five studies. Their death rate was slightly lower than that of the untreated group (2.3 vs. 2.8 per 100 person-years).
Seven studies evaluating CBT after a stroke showed a significantly lower recurrence rate of 2.7 strokes per 100 person-years and a death rate of 0.6.
“If CBT is not available as the initial strategy for primary and secondary stroke prevention, HU is a reasonable alternative compared to no therapy,” the team wrote.
Five studies, all from HICs, reported that stem cell transplants were the most effective in reducing stroke recurrence, at a rate of one per 100 person-years. The pooled mortality rate was 0.6.
Our pooled data analysis has an immediate impact on the care of children with SCA living in LMIC, demonstrating that untreated strokes and the first 12-24 months after a stroke are critical to prevent stroke recurrence and death.
Pooled data from seven studies of RVS showed a stroke recurrence rate of 3.3 per 100 person-years, witht most of these events occurring within the first month after surgery. The death rate was 1.4 per 100 person-years.
Further analyses demonstrated that in children who received hydroxyurea or CBTs, those with persistent abnormalities in TCD blood flow remained at high risk of stroke even while receiving therapy.
The findings support the need to conduct “TCD measurements 3 months after initiating therapy with [hydroxyurea] or CBT for all children with abnormal TCD velocities,” the researchers wrote.
Overall, “our pooled data analysis has an immediate impact on the care of children with SCA living in LMIC, demonstrating that untreated strokes and the first 12-24 months after a stroke are critical to prevent stroke recurrence and death,” they concluded.
