Meschia et al Guidelines for the Primary Prevention of Stroke 3785 Periodic red cell transfusion is the only intervention proven in randomized trials to prevent stroke in patients with SCD. STOP randomized children with SCD who had abnormal high-risk TCD profiles to either standard care, which included episodic transfusion as needed for pain, or periodic red cell transfusion an average of 14 times per year for >2 years with a target reduction of hemoglobin S from a baseline of >90% to <30%. The risk of stroke was reduced from 10%/y Unless exchange methods in which blood is removed from the patient with each transfusion are used, long- term transfusion results in iron toxicity that requires treatment In STOP, there was no evidence of transfu- sion-related infection, but iron overload and alloimmunization remain important transfusion risks.582 To address these risks, STOP II tested whether long-term transfusions for primary stroke prevention could be safely discontinued after at least 30 months (range, 30 91 months) in children who had not had an overt stroke and who had reversion to low-risk TCD velocities (time-averaged mean velocity in middle cerebral or internal carotid artery, <170 cm/s) with long-term transfusion therapy. The study end point was the first occurrence of rever- sion of TCD to abnormal confirmed by 2 TCDs with mean velocities of 200 cm/s or stroke. The study was terminated earlier than planned when an interim analysis showed worse outcomes with discontinuation of transfusion therapy. 