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.
"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). "
[Show abstract][Hide abstract] 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
[Show abstract][Hide abstract] ABSTRACT: The venom of Loxosceles reclusa (Brown Recluse spider) can cause a severe, life-threatening hemolysis in humans for which no therapy is currently available in the USA beyond supportive measures. Because this hemolysis is uncommon, relatively little is known about its clinical manifestation, diagnosis, or management. Here, we aimed to clarify the clinical details of envenomation, to determine the efficacy of the complement inhibitor eculizumab to prevent the hemolysis in vitro, and to investigate markers of exposure to Brown Recluse venom.
We performed a 10-year chart review of cases of Brown Recluse spider bite-mediated hemolysis at our institution. We also designed an in vitro assay to test the efficacy of eculizumab to inhibit hemolysis of venom exposed red blood cells. Finally, we compared levels of CD55, CD59 and glycophorin A on venom exposed versus venom-naïve cells.
Most victims of severe Brown Recluse spider mediated hemolysis at our institution are children and follow an unpredictable clinical course. Brown Recluse spider bite mediated hemolysis is reduced by 79.2% (SD=18.8%) by eculizumab in vitro. Erythrocyte glycophorin A, but not CD55 or CD59, is reduced after red blood cells are incubated with venom in vitro.
Taken together, our laboratory data and clinical observations indicate that L. reclusa venom exposure results in non-specific antibody and complement fixation on red blood cells, resulting in complement mediated hemolysis that is curtailed by the complement inhibitor eculizumab in vitro. Glycophorin A measurement by flow cytometry may help to identify victims of L. reclusa envenomation.
PLoS ONE 09/2013; 8(9):e76558. DOI:10.1371/journal.pone.0076558 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Sickle cell disease (SCD) is the name for a group of related blood disorders caused by an abnormal hemoglobin molecule that polymerizes on deoxygenation. SCD affects the entire body, and the multisystem pathophysiology begins in infancy. Thanks to prognostic and therapeutic advancements, some forms of SCD-related morbidity are decreasing, such as overt stroke. Almost all children born with SCD in developed nations now live to adulthood, and lifelong multidisciplinary care is necessary. This article provides a broad overview of SCD in childhood, from newborn screening through transition to adult medical care.
Pediatric Clinics of North America 12/2013; 60(6):1363-81. DOI:10.1016/j.pcl.2013.09.006 · 2.12 Impact Factor
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