Primary and secondary stroke prophylaxis in children with sickle cell anemia: a meta-analysis.

We conducted a pooled analysis to evaluate the effectiveness of hydroxyurea (HU), chronic blood transfusion (CBT), myeloablative allogeneic hematopoietic stem cell transplant (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 ≥6 patients published before January 2025. Four reviewers reviewed all studies to arrive at a consensus assessment. The stroke rates (per 100 person-year) for primary stroke prevention in children with transcranial Doppler measurement ≥200 cm/s were as follows: no therapy, 10.7; after initial HU, 1.0; and 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 the time-dependent stroke recurrence rate, resulting in an overestimation of their therapeutic benefit compared to the stroke recurrence rates before the intervention. In low- and middle-income countries (LMICs), where ∼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 2 studies; in the only randomized controlled trial for secondary stroke prevention with initial HU (SPRING trial n = 101), 38% (5 of 13) of the deaths occurred within the first year. For children in LMICs where local HU costs <$0.20 per day, HU is a practical, inexpensive option for primary and secondary stroke prevention.

Duke Scholars

Author Malcolm R DeBaun Orthopaedic Surgery