Lessons from the stroke prevention trial in sickle cell anemia (STOP) study

Stroke is generally uncommon in children, but sickle cell disease is associ ated with a high risk of stroke in the early yeats of childhood. Large cere bral arteries, especially the middle cerebral and intracranial internal car otid, develop stenosis that predisposes to ischemic stroke. Noninvasive pre diction of risk using transcranial Doppler ultrasonography made it possible to test primary stroke prevention in a clinical trial comparing chronic bl ood transfusion with standard care. A consortium of 14 clinical centers con ducted a randomized clinical Mal (Stroke Prevention in Sickle Cell Anemia-t he "STOP" study) to test a strategy to prevent first stroke in children wit h sickle cell disease. Over 2000 children were screened with transcranial D oppler ultrasonography and of these, 130 with elevated blood velocity indic ating high risk were enrolled in the trial. Regular red cell transfusions s ufficient to reduce the percentage of Hb S gene product from over 90 to les s than 30 of total hemoglobin was associated with a marked reduction in str oke. The untreated risk of 10% per year was reduced over 90% with treatment , an effect sufficient to cause early termination of the trial. Although tr eatment was unblinded, the design included blinded adjudication of possible stroke by a panel of neurologists remote from the study sites. The study l ed to a Clinical Alert, issued by the National Heart, Lung, and Blood Insti tute, recommending screening and consideration of treatment in children wit h sickle cell disease and 2 to 16 years of age who are at risk based on tra nscranial Doppler ultrasonography, and who have not had stroke.