Primary and Secondary Stroke Prophylaxis in Children with Sickle Cell Anemia: A Meta-Analysis Open Access

We conducted a pooled analysis to evaluate the effectiveness of hydroxyurea (HU), chronic blood transfusions (CBT), myeloablative allogeneic hematopoietic stem cell transplants (HCT) with a matched related donor, and revascularization surgery (RVS) in children with sickle cell anemia (SCA). We compared the interventions with no therapy for primary and secondary stroke prevention. The Medline and EMBASE databases were searched for articles that included six or more patients published before January 2025. Four reviewers reviewed all studies to arrive at a consensus assessment. The stroke rates for primary stroke prevention in children with transcranial Doppler measurement > 200 cm/sec were per 100 person-years: no therapy, 10.7; after initial HU, 1.0; after initial CBT, 1.0. The stroke recurrence rates for secondary stroke prevention per 100 person-years were 19.6 after no therapy, 3.5 after initial HU, 2.7 after initial CBT, 1.0 after HCT, and 3.3 after RVS. Neither the HCT nor the RVS study adjusted for time-dependent stroke recurrence rate, resulting in an overestimation of their therapeutic benefit compared to the stroke recurrence rates before the intervention. In low-middle-income countries (LMICs), where approximately 99% of all children with SCA are born, the stroke recurrence rate in untreated children in the first year was 36.4 to 51.4 strokes per 100 person-years, in two studies; in the only randomized controlled trial of HU, 38% of children died within the first year. For children in LMICs where local hydroxyurea costs < $0.20 per day, HU is a practical, inexpensive option for primary and secondary stroke prevention.