Diverse manifestations of acute sickle cell hepatopathy in pediatric patients with sickle cell disease: A case series

The hepatic complications of sickle cell disease (SCD) are associated with increased morbidity and mortality in adults; children usually survive but may suffer significant sequelae. Few diagnostic tools differentiate the various hepatic manifestations of SCD. Why patients exhibit one hepatic pathology versus another is unclear. We report four pediatric patients with hemoglobin SS disease with diverse manifestations of acute hepatic involvement including acute sickle hepatic crisis, hepatic sequestration, sickle cell intrahepatic cholestasis, and a non‐SCD cause of hepatopathy in a patient with viral hepatitis. These complications require a systematic approach to extensive evaluation and coordinated multidisciplinary care.     

Potential role for statins in sickle cell disease

The complex pathophysiology of sickle cell disease (SCD) is remarkably similar to that observed in other chronic vascular diseases and involves multiple biologic pathways triggered by ischemia reperfusion injury, coagulation activation, and inflammation. Statins are potent lipid‐lowering agents commonly used to reduce the risk of cardiovascular disease. Independent of their lipid lowering effect, statins have been shown to down‐regulate inflammatory mediators and endothelial adhesion molecules, reduce tissue factor expression and restore nitric oxide bioavailability. The pleiotropic effects of statins make these agents attractive therapeutic candidates for SCD. This article reviews available evidence for the potential role of statins in SCD. Pediatr Blood Cancer 2013; 60: 550–557. © 2012 Wiley Periodicals, Inc.     

Reversible posterior leuko‐encephalopathy in children with sickle cell disease

Children with sickle cell disease (SCD) have high risk of neurologic morbidity and mortality, such as strokes, silent infarcts and TIA's. A retrospective review of magnetic resonance imaging and magnetic resonance angiography identified eight children with radiological and clinical characteristics of reversible posterior encephalopathy (RPLS). These patients had no evidence of previous cerebral infarcts or vasculopathy. Three have died during the 5‐year follow up; one developed a stroke and one a conditional TCD. RPLS needs to be considered in the differential diagnosis of children with SCD that present with acute neurological changes, especially if they are already been hospitalized. Pediatr Blood Cancer 2009;52:373–375. © 2008 Wiley‐Liss, Inc.     

Impact of proximity to comprehensive sickle cell center on utilization of healthcare services among children with sickle cell disease

Background

The impact of comprehensive care on utilization of healthcare services by children with sickle cell disease (SCD) has not been fully evaluated. We compared the medical care utilization and mortality in children less than 20 years of age with SCD in four regions in the state of Tennessee with and without a comprehensive sickle cell center (CSCC).

Methods

Rates of hospitalizations, outpatient and emergency department (ED) visits, and deaths were measured in a cohort of children aged <20 years with SCD, enrolled in TennCare, from January 1995 to December 2002. TennCare data linked to Tennessee vital records were used to define the population and identify the outcomes. The patients were classified into one of four regions based on their residential address on the day of their hospitalization or outpatient visit.

Results

The cohort consisted of 1,214 children with 6,393 person‐years of follow‐up. Fifty‐six percent of patients resided in the region with the CSCC. This region had the highest overall rates of hospitalization for all children (P < 0.001), while ED and outpatient visits were higher in other areas. The death rates ranged from 1.8 to 4.3 per 1,000 person‐years in the four regions and did not represent statistically significant differences.

Conclusion

No clear pattern of improved utilization of medical care services were identified in relation to proximity of residence to a CSCC. This cohort was not large enough to detect small differences in death rates. In addition, other outcomes that incorporate quality of life measures may be more sensitive to differences in medical care. Pediatr Blood Cancer 2008;50:66–71. © 2006 Wiley‐Liss, Inc.     

High birth prevalence of sickle cell disease in Northwestern Tanzania

1 Background

Worldwide, hemoglobinopathies affect millions of children. Identification of hemoglobin disorders in most sub‐Saharan African countries is delayed until clinical signs of the disease are present. Limited studies have been conducted to understand their prevalence and clinical presentation among newborns in resource‐limited settings.

2 Methodology

This was a prospective cohort study. Newborns (aged 0–7 days) at two hospitals in Northwestern Tanzania were enrolled and followed prospectively for 6 months. Clinical and laboratory information were collected at baseline. Participants were screened for hemoglobinopathies using high‐performance liquid chromatography. Clinical and laboratory follow‐up was performed at 3 and 6 months for those with hemoglobinopathies as well as a comparison group of participants without hemoglobinopathies.

3 Results

A total of 919 newborns were enrolled. Among these, 1.4% (13/919) had sickle cell anemia or Hb S/β⁰‐thalassemia (Hb FS), and 19.7% (181/919) had sickle cell trait or Hb S/β⁺ thalassemia (Hb FAS). Furthermore, 0.2% (two of 919) had β⁺‐thalassemia. Red cell indices compared between Hb FS, Hb FAS, and Hb FA were similar at baseline, but hemoglobin was lower and red cell distribution width was higher in children with Hb FS at 3‐ and 6‐month follow‐up. Febrile episodes were more common for children with Hb FS at 3‐ and 6‐month follow‐up.

4 Conclusion

The prevalence of sickle cell disease among neonates born in Northwestern Tanzania is one of the highest in the world. Newborn screening is needed early in life to identify neonates with hemoglobinopathies so that clinical management may commence and morbidity and mortality related to hemoglobinopathies be reduced.     

Prolonged QT interval in pediatric sickle cell disease

We recently cared for a patient with sickle cell disease (SCD) who presented with cardiac arrest and was found to have a prolonged corrected QT interval (QTc). This prompted us to perform a retrospective review of all electrocardiograms performed in patients with SCD during the last two years. Among 142 patients with ECG results, we identified 12 patients (8 males and 4 females), who had one or more documented measurements of prolonged QTc intervals. The relatively high prevalence of borderline or moderately prolonged QTc intervals in our patient population warrants further investigation.     

Hematopoietic stem cell transplantation for sickle cell disease: Progress and challenges

Sickle cell disease (SCD) presents challenges to hematopoietic stem cell transplantation (HSCT), including donor availability and morbidity with age/disease severity. However, severe SCD causes irreversible organ damage that HSCT can mitigate. This benefit must be balanced against preparative regimen toxicity, graft‐versus‐host disease, and mortality risk. We review efforts to balance HSCT complications with the promise of cure, and knowledge gaps that warrant further investigation. We highlight the burden of SCD, HSCT risks and benefits, and SCD families’ approach to this balance. We emphasize the necessity for information exchange to ensure a joint decision‐making process between providers and patients.