There are no randomized trials for antithrombot- ics for secondary stroke prevention in SCD. Caution is advised when considering antithrombotics for second- ary stroke prevention in patients with SCD because the stroke mechanism is less certain and patients with SCD are also at higher risk for hemorrhagic stroke. If there is evidence for other stroke mechanisms in a patient with SCD (ie, atherosclerosis), then it would be reasonable to administer antithrombotics as supported elsewhere in this guideline. Recommendation-Specific Supportive Text 1. The recommendations for treatment of patients with SCD are based on stroke primary prevention studies in a pediatric population and a secondary stroke prevention study in a population of pediat- ric patients with SCD with silent cerebral infarc- tions (SIT [Silent Cerebral Infarct Transfusion] multi-center clinical trial).671 The STOP trial was a randomized, placebo-controlled trial that showed that a long-term prophylactic transfusion strategy was effective for the primary prevention of stroke in children with SCD and high TCD velocities.655 Blood transfusion was used because it was dem- onstrated effective in reducing recurrent clinical ischemic stroke and progression of arterial steno- sis in a series of children with SCD.656 This was associated with a reduction in the rate of recurrent stroke during a mean follow-up of 3 years com- pared with historical control subjects.657 Most of the patients in the series were children, and it is unclear whether adults have the same untreated risk or benefit from treatment.658 Regular transfu- sions are associated with long-term complications, especially iron overload, typically requiring iron che- lation therapy. The SIT trial showed reduced recur- rent stroke in children with SCD and silent cerebral infarct who underwent transfusion compared with 2. 