Stroke in adults with sickle cell disease: Outcomes of a non-HbS-targeted combined hydroxyurea and manual exchange transfusion strategy

Abstract ‏Background: ‏Ischemic stroke is a serious complication of sickle cell disease (SCD). While most secondary prevention strategies are based on pediatric data, adult-specific evidence—particularly regarding hemoglobin S (HbS) thresholds and transfusion intervals—remains limited. ‏Objective: ‏To evaluate stroke recurrence in adult SCD patients treated with a combined hydroxyurea (HU) and manual blood exchange transfusion (BET) strategy without targeting HbS <30%, and to assess the safety of a 4–8 week BET interval. ‏Methods: ‏This retrospective single-center study included adult SCD patients (≥18 years) with ischemic stroke managed at King Fahad Hospital, Hofuf, Saudi Arabia, between May 2017 and April 2025. Patients received HU and scheduled manual BET every 4–8 weeks. Data collected included demographics, comorbidities, genotypes, HbS% trends, treatment details, and stroke recurrence. Three patients were excluded: one due to pediatric stroke onset and two due to insufficient follow-up. Median follow-up was 43.6 months. ‏Results: ‏Fifteen patients were included. At stroke onset, median HbS% was 79% (range: 70–87%). During follow-up, the median highest and lowest HbS% were 71.5% and 35.0%, respectively; no patient achieved HbS <30%. Only one patient (6.7%) experienced recurrent stroke, occurring 36 months after the initial event. ‏Conclusion: ‏A combined HU and manual BET strategy administered every 4–8 weeks without targeting HbS <30% was associated with a low rate of stroke recurrence in adults with SCD. These findings support a feasible , individualized approach to secondary stroke prevention that may differ from pediatric-based transfusion thresholds.