 The STOP Stroke Prevention in Sickle Cell Anemia trial, a multicenter, randomized, controlled trial for primary stroke demonstrated that monthly blood transfusions, when compared to observation alone, significantly reduced the risk of primary stroke for children with SCA whose TCD velocity exceeded 200 cmsec. Despite the STOP trials clear results, there are unresolved issues regarding TCD and stroke risk in children with SCA. First, the predictive value of an abnormal result is not compelling since less than a third of children with an abnormal TCD velocity and even fewer with conditional results will ever develop a clinical stroke. There is also discordance between TCD and MRI results. Only 40 of children with abnormal TCD velocity will have abnormalities on brain MRI Wang, et al. J Pediatr HematolOncol 2000;224:335-339, Pegelow, et al. Arch Neurol 2001;58:2017-2021. There are also well recognized risks of chronic blood transfusions, including iron overload and alloimmunization, and the necessary duration of transfusion protection for children with abnormal TCD velocity is unknown. Unfortunately, there are currently no therapeutic options besides blood transfusions for patients with SCA and an abnormal TCD velocity. 