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 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.