https://orcid.org/0000-0002-4473-5821
Key Points
A partnership with Dominican Republic built local capacity and established a sickle cell TCD screening program for primary stroke prevention
Hydroxyurea lowers TCD velocities, and maximum tolerated dose provides extended stroke prevention and clinical benefits in Hispanic children
Sickle cell anemia (SCA) is recognized globally, but little is known about affected Hispanic populations. In partnership with Dominican Republic, a Hispanic Caribbean Island with a large SCA population, a TCD screening program provided hydroxyurea to children with conditional velocities. Building local capacity, ten Dominican medical graduates were certified in TCD examinations and trained in hydroxyurea management. Stroke Avoidance for Children in REpública Dominicana trial (SACRED, NCT02769845) enrolled 283 children with average age 8.7±3.4 years and 130 (46%) females. At initial screening, treatment-naïve children with conditional velocities (170-199 cm/sec) were younger (6.6±2.7 versus 8.9±3.4 years, p=.0002) and more anemic (hemoglobin 7.4±0.8 versus 8.0±1.2 g/dL, p=.0046) than children with normal screening velocities (<170 cm/sec). Among 57 treatment-naïve children receiving six months of fixed-dose hydroxyurea at 20 mg/kg/day, average TCD velocities decreased 20 cm/sec and 61% became normal. Compared to fixed-dose hydroxyurea, dose escalation to maximum tolerated dose (MTD) led to fewer sickle-related events with incidence rate ratio 0.59, 95% Confidence Intervals 0.36-0.98, p=0.0420. At MTD, TCD benefits were sustained over 5 years, with 81% reverting to normal and average TCD velocity decrease of 27 cm/sec. Brain MRI documented substantial baseline parenchymal disease; during hydroxyurea treatment 10% developed new vasculopathy, plus one stroke and one death. SACRED documents a high burden of cerebrovascular disease among Hispanic children with SCA, but also demonstrates the feasibility of partnership to establish TCD screening programs, the utility of hydroxyurea to reduce TCD velocities and reduce stroke risk, and the sustained benefits of hydroxyurea dose escalation.
