In 2020, the SPRING research team completed a multicenter phase III randomized controlled trial for primary stroke prevention in children with sickle anemia, demonstrating that children with an annual 10% stroke risk because of a high velocity of blood flow in their brain could be treated with either low or moderate dose hydroxyurea for a significant decrease in strokes. This study proposes an open-label, single-arm, type I hybrid trial (phase IV trial) for primary stroke prevention initially with low-dose hydroxyurea and subsequently with moderate-dose hydroxyurea based after at least two severe pain events requiring physician contacts during the trial and assessment of ways to maintain the sustainability of stroke prevention programs. We will conduct a cost-effective analysis to determine the sustainability, relative cost, and effectiveness of the hydroxyurea dose on stroke prevention and healthcare utilization.