Acute silent cerebral ischemia and infarction during acute anemia in children with and without sickle cell disease

Department of Pediatrics, University of Texas Southwestern Medical Center, and Children's Medical Center, Dallas, TX, United States
Blood (Impact Factor: 10.45). 09/2012; 120(19). DOI: 10.1182/blood-2012-01-406314
Source: PubMed


We hypothesized that the silent cerebral infarcts (SCI), which affect up to 40% of children with sickle cell disease (SCD), could occur in the setting of acute anemic events. We conducted a prospective observational study of children with and without SCD hospitalized for an illness associated with acute anemia. We identified acute silent cerebral ischemic events (ASCIE) in 4/22 (18.2%) with SCD and in 2/30 (6.7%) without SCD, using diffusion-weighted magnetic resonance imaging (DWI). Children with ASCIE had lower hemoglobin concentration than those without (median 3.1 vs 4.4 g/dl, p=0.003). The unique temporal features of cerebral infarction on DWI permit estimation of incidence rates for ASCIE of 421 (95% C.I. 155-920) per 100 patient years during acute anemic events for all patients. For children with SCD, the estimated incidence was 663 (95% C.I. 182-1707) which is much higher than reported in longitudinal studies of silent or overt strokes in SCD. Acute anemic events are common in children with SCD and therefore could partially account for the high SCI prevalence. Some ASCIE (1/4 in our study) may be reversible. Alterations in management may be warranted for all children with severe anemia to identify unrecognized ischemic brain injury that may have permanent neurocognitive sequelae.

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    • "Silent infarcts were not systematically evaluated in our cohort because magnetic resonance imaging (MRI) was mainly done for macrocerebrovascular indications. We therefore could determine the impact of AAE on the occurrence of silent infarcts in the G6PD-deficient group, as recently described for SCA patients after AAE (Dowling et al, 2012). Moreover we did not genotype non G6PD-deficient patients, precluding any discussion regarding allele A versus allele B G6PD impact on silent infarct occurrence as described recently in the Silent Infarct Trial (SIT) (Thangarajh et al, 2012). "
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    ABSTRACT: In patients with sickle cell anaemia (SCA), concomitant glucose-6-phosphate dehydrogenase (G6PD) deficiency is usually described as having no effect and only occasionally as increasing severity. We analysed sequential clinical and biological data for the first 42 months of life in SCA patients diagnosed by neonatal screening, including 27 G6PD-deficient patients, who were matched on sex, age and parents' geographic origin to 81 randomly selected patients with normal G6PD activity. In the G6PD-deficient group, steady-state haemoglobin was lower (-6·2 g/l, 95% confidence interval (CI), [-10·1; -2·3]) and reticulocyte count higher (247 × 10(9) /l, 95%CI, [97; 397]). The acute anaemic event rate was 3 times higher in the G6PD-deficient group (P < 10(-3) ). A higher proportion of G6PD-deficient patients required blood transfusion (20/27 [74%] vs. 37/81 [46%], P < 10(-3) ), for acute anaemic events, and also vaso-occlusive and infectious events. No significant between-group differences were found regarding the rates of vaso-occlusive, infectious, or cerebrovascular events. G6PD deficiency in babies with SCA worsens anaemia and increases blood transfusion requirements in the first years of life. These effects decrease after 2 years of age, presumably as the decline in fetal haemoglobin levels leads to increased sickle cell haemolysis and younger red blood cells with higher G6PD activity.
    British Journal of Haematology 10/2013; 163(5). DOI:10.1111/bjh.12590 · 4.71 Impact Factor
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    PLoS ONE 09/2013; 8(9):e76558. DOI:10.1371/journal.pone.0076558 · 3.23 Impact Factor
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