Stroke incidence and phenotype in Saudi patients with sickle cell disease: A longitudinal cohort study

Stroke is a major cause of morbidity in sickle cell disease (SCD); however, contemporary longitudinal data from Saudi cohorts remain limited. We examined stroke incidence, phenotype and laboratory correlates in 195 patients with homozygous sickle cell anaemia (HbSS) or sickle β⁰-thalassaemia (HbS/β⁰), predominantly from southwestern regions (median age at enrolment, 16.5 years; 53% male; median baseline haemoglobin, 8.9 g/dL; fetal haemoglobin [HbF], 10.5%), followed for a median of 13.5 years (2009-2025; 2173 patient-years). Hydroxyurea (hydroxycarbamide) use increased from 44% at enrolment to 85% at follow-up. Fourteen strokes (13 ischaemic, 1 haemorrhagic) occurred at a median age of 28 years, an overall incidence of 0.64 per 100 patient-years (0.39 in <18 years to 0.93 in >30 years), with no overt stroke before age 10. By age 30, cumulative incidence of overt ischaemic stroke and silent cerebral infarcts (SCIs) reached 5.0% and 18.6% respectively. In age- and sex-adjusted models, higher baseline lactate dehydrogenase (LDH) was associated with ischaemic stroke (incidence rate ratio [IRR], 1.46 per 100 U/L; 95% confidence interval [CI], 1.11-1.91; p = 0.007); HbF showed a protective trend (IRR 0.55 per 5% increase; 95% CI, 0.29-1.06; p = 0.07). This age-related stroke pattern without a childhood peak may reflect higher baseline HbF, expanded hydroxyurea use, and supportive care improvements, although population-specific modifiers cannot be excluded.