Global burden disparities and unmet needs of stroke in sickle cell disease

Abstract

Sickle cell disease (SCD) is a major global health burden, affecting millions worldwide, particularly in sub-Saharan Africa and India. Stroke is one of its most severe complications, causing lifelong disability and early mortality. While largely preventable in high-income countries, stroke in SCD remains common in low- and middle-income settings and is increasingly recognized in adults, reflecting persistent inequities in care. Stroke in SCD arises from chronic hemolytic anemia, vaso-occlusion, endothelial dysfunction, inflammation, and adverse social determinants of health. Without intervention, children face a 10–15% lifetime risk of overt stroke, and silent cerebral infarcts affect more than half of individuals by adulthood. Transcranial Doppler screening combined with chronic transfusion therapy has reduced pediatric stroke incidence by over 90% in high-resource settings, representing a major public health success. Hydroxyurea and transfusion are effective and scalable alternatives for primary and secondary prevention. However, stroke prevention efforts often diminish after childhood, and robust evidence for adult-focused strategies remains limited despite the rising adult stroke burden. Global disparities persist due to limited newborn screening, shortages of trained healthcare personnel, inadequate transfusion and neuroimaging infrastructure, and fragmented transition from pediatric to adult care. Acute stroke management is further constrained in high-burden regions by delayed presentation and lack of specialized services. Reducing the global burden of SCD-related stroke requires integrating evidence-based prevention into broader health systems, emphasizing lifelong surveillance, adult-focused research, equitable access to care, and alignment with global noncommunicable disease frameworks.