Silent cerebral infarcts occur despite regular blood transfusion therapy after first strokes in children with sickle cell disease

Abstract

Children with sickle cell disease (SCD) and strokes receive blood transfusion therapy for secondary stroke prevention; despite this, approximately 20% experience second overt strokes. Given this rate of second overt strokes and the clinical significance of silent cerebral infarcts, we tested the hypothesis that silent cerebral infarcts occur among children with SCD being transfused for secondary stroke prevention. A prospective cohort enrolled children with SCD and overt strokes at 7 academic centers. Magnetic resonance imaging and magnetic resonance angiography of the brain were scheduled approximately every 1 to 2 years; studies were reviewed by a panel of neuroradiologists. Eligibility criteria included regularly scheduled blood transfusion therapy. Forty children were included; mean pretransfusion hemoglobin S concentration was 29%. Progressive cerebral infarcts occurred in 45% (18 of 40 children) while receiving chronic blood transfusion therapy; 7 had second overt strokes and 11 had new silent cerebral infarcts. Worsening cerebral vasculopathy was associated with new cerebral infarction (overt or silent; relative risk = 12.7; 95% confidence interval, 2.65-60.5, P = .001). Children with SCD and overt strokes receiving regular blood transfusion therapy experience silent cerebral infarcts at a higher rate than previously recognized. Additional therapies are needed for secondary stroke prevention in children with SCD.

Figure 1

Children with SCD receiving regular blood transfusion therapy for secondary prophylaxis of strokes. Subjects' clinical records were reviewed to determine the occurrence of second overt strokes and TIAs. MRI of the brain was used to determine the occurrence of silent cerebral infarcts. Shaded boxes represent children with second overt strokes or progressive silent cerebral infarctions.

Figure 2

Survival free of new overt or silent cerebral infarcts in children with SCD while on transfusion therapy for secondary stroke prophylaxis. Participants with progressive overt and silent cerebral infarction, stratified for the absence (solid line) or the presence (dashed line) of progressive cerebral vasculopathy during chronic blood transfusion therapy. Vertical lines represent censored cases. Median event-free interval for new silent or overt infarction was 3.2 years for the group with progressive vasculopathy, compared with median event-free interval not reached in the group without progressive vasculopathy (Mantel-Cox log-rank, P = .001).

Figure 3

Survival free of detection of new silent cerebral infarcts in children with SCD while on transfusion therapy for secondary stroke prophylaxis. Participants with progressive silent infarctions only, stratified for the absence (solid line) or the presence (dashed line) of progressive cerebral vasculopathy while receiving chronic blood transfusion therapy. Vertical lines represent censored cases. Median progressive silent infarction only interval was 3.6 years for those with progressive vasculopathy versus median progressive silent infarct–free interval not reached for those without progressive vasculopathy (Mantel-Cox log-rank, P = .017).

Figure 4

Survival free of second overt strokes in children with SCD while on transfusion therapy for secondary stroke prophylaxis. Participants with second overt strokes, stratified for the absence (solid line) or the presence (dashed line) of progressive cerebral vasculopathy while receiving chronic blood transfusion therapy. Vertical lines represent censored cases. Median second overt stroke–free interval was 7.6 years for those with progressive vasculopathy versus median stroke-free interval not reached for those without progressive vasculopathy (Mantel-Cox log-rank, P = .003).