Controlled Trial of Transfusions for Silent Cerebral Infarcts in Sickle Cell Anemia

Abstract

BACKGROUND Silent cerebral infarcts are the most common neurologic injury in children with sickle cell anemia and are associated with the recurrence of an infarct (stroke or silent cerebral infarct). We tested the hypothesis that the incidence of the recurrence of an infarct would be lower among children who underwent regular blood-transfusion therapy than among those who received standard care. METHODS In this randomized, single-blind clinical trial, we randomly assigned children with sickle cell anemia to receive regular blood transfusions (transfusion group) or standard care (observation group). Participants were between 5 and 15 years of age, with no history of stroke and with one or more silent cerebral infarcts on magnetic resonance imaging and a neurologic examination showing no abnormalities corresponding to these lesions. The primary end point was the recurrence of an infarct, defined as a stroke or a new or enlarged silent cerebral infarct. RESULTS A total of 196 children (mean age, 10 years) were randomly assigned to the observation or transfusion group and were followed for a median of 3 years. In the transfusion group, 6 of 99 children (6%) had an end-point event (1 had a stroke, and 5 had new or enlarged silent cerebral infarcts). In the observation group, 14 of 97 children (14%) had an end-point event (7 had strokes, and 7 had new or enlarged silent cerebral infarcts). The incidence of the primary end point in the transfusion and observation groups was 2.0 and 4.8 events, respectively, per 100 years at risk, corresponding to an incidence rate ratio of 0.41 (95% confidence interval, 0.12 to 0.99; P = 0.04). CONCLUSIONS Regular blood-transfusion therapy significantly reduced the incidence of the recurrence of cerebral infarct in children with sickle cell anemia. (Funded by the National Institute of Neurological Disorders and Stroke and others; Silent Cerebral Infarct Multi-Center Clinical Trial ClinicalTrials.gov number, NCT00072761, and Current Controlled Trials number, ISRCTN52713285.)

Encephaloduroarteriosynangiosis and encephalomyoarteriosynangiosis for treatment of moyamoya syndrome in pediatric patients with sickle cell disease

“…10 Chronic transfusion therapy is the mainstay treatment for primary and secondary neurovascular complications. 2,3,12,22,30,35 Although chronic transfusion therapy prevents initial and recurrent stroke in the majority of patients, some patients on chronic transfusion therapy continue to experience strokes and develop progressive vascular disease. 19,30 The progression of their vascular disease triggers the development of a fragile network of arteries that resembles MMD and is present in 30%-43% of patients with SCD and a history of stroke.…”

Evolution of sickle cell disease from a life‐threatening disease of children to a chronic disease of adults: The last 40 years

“…Based on the morbid and progressive nature of SCI, the NINDS sponsored the Silent Infarct Transfusion (SIT) trial, a multicenter randomized trial in which children with SCA and SCI were assigned to receive standard care (observation group) or regular blood-transfusion therapy (transfusion group). The incidence of stroke in the transfusion and observation groups was 2.0 and 4.8 events per 100 patient-years, respectively, corresponding to a 58% relative risk reduction in overt strokes or new or enlarged silent cerebral infarcts (P 5 0.04) [84].…”

Sickle Cell Disease

“…Sickle Cell Disease 10 Ware et al, 11 and Yawn et al 12 Data on availability in low-resource areas are from Bello-Manga et al 13 HbS denotes sickle hemoglobin.…”