Newborn screening for hemoglobinopathies in California

Background

Newborn screening (NBS) for hemoglobinopathies facilitates early identification of affected individuals to ensure the prompt institution of comprehensive medical care for affected newborns in California. When linked to extensive follow‐up and education, NBS has been shown to significantly reduce mortality in children with sickle cell disease. Due to changing immigration patterns from Asia and Latin America, the State of California has witnessed an increased prevalence of clinically significant hemoglobin (Hb) disorders, including those resulting from novel genotypes. In 1999, newborn screening for Hb H disorders was incorporated in the statewide hemoglobinopathy screening program.

Procedure

Primary screening for hemoglobin variants was performed using high performance liquid chromatography. Confirmatory testing on hemoglobinopathy mutations was performed by electropheresis techniques and genotyping methods.

Results

Of 530,000 newborn samples screened annually in California, 2,118 samples were referred to the Hemoglobin Reference Laboratory (HRL) for confirmatory testing between January 1, 1998 and June 30, 2006 (0.05%). Sickle cell disease was most frequently observed (1 in 6,600 births) followed by α‐thalassemia (1 in 9,000 births) and β‐thalassemia disease (1 in 55,000 births). The confirmatory analysis modified the initial screening in 5% of cases and revealed 25 rare or new genotypes. Diverse ethnicities were associated with hemoglobin mutations including Southeast Asian, Black, Indian/Asian, Middle Eastern, and Hispanic.

Conclusions

The California hemoglobinopathy screening program provides accurate diagnosis of hemoglobinopathies. Increasing incidence of diverse mutations require new strategies of laboratory screening, counseling, and patient management. Pediatr Blood Cancer 2009;52:486–490. © 2008 Wiley‐Liss, Inc.     

Hydroxyurea therapy in UK children with sickle cell anaemia: A single‐centre experience

1 Introduction

Despite the demonstrated efficacy of hydroxyurea therapy, children with sickle cell anaemia in the UK are preferentially managed with supportive care or transfusion. Hydroxyurea is reserved for children with severe disease phenotype. This is in contrast to North America and other countries where hydroxyurea is widely used for children of all clinical phenotypes. The conservative UK practice may in part be due to concerns about toxicity, in particular marrow suppression with high doses, and growth in children.

2 Methods and results

We monitored 37 paediatric patients with sickle cell anaemia who were treated with hydroxyurea at a single UK treatment centre. Therapy was well tolerated and mild transient cytopenias were the only toxicity observed. Comparative analysis of patients receiving ≥26 mg/kg/day versus <26 mg/kg/day demonstrates increasing dose has a significant positive effect on foetal haemoglobin (Hb; 29.2% vs. 20.4%, P = 0.0151), mean cell volume (94.4 vs. 86.5, P = 0.0183) and reticulocyte count (99.66 × 10⁹/l vs. 164.3 × 10⁹/l, P = 0.0059). Marrow suppression was not a clinical problem with high‐dose treatment, Hb 92.25 g/l versus 91.81 g/l (ns), neutrophil count 3.3 × 10⁹/l versus 4.8 × 10⁹/l (ns) and platelet count 232.4 × 10⁹/l versus 302.2 × 10⁹/l (ns). Normal growth rates were maintained in all children. Good adherence to therapy was a significant factor in reducing hospitalisations.

3 Conclusion

This study demonstrates the effectiveness and safety in practice of high‐dose hydroxyurea as a disease‐modifying therapy, which we advocate for all children with sickle cell anaemia.     

Neonatal Screening of Sickle Cell Anemia: A Preliminary Report

Objective

To evaluate feasibility of systematic neonatal screening for sickle cell disease in Chhattisgarh.

Methods

A pilot study was done from February 2008 through January 2009 in Department of Pediatrics &; Neonatology, Pt. J.N.M. Medical College &; Dr.B.R.A.M. Hospital, Raipur (Chhattisgarh) on a total of 1,158 neonates. Blood samples from the neonates were taken after 48 h of birth on filter paper for detection of sickle cell anemia using Biorad hemoglobin variant Neonatal sickle cell short programme by high performance liquid chromatography (HPLC). On follow up, cases were analyzed by HPLC using Beta thalassemia short program to rule out false negative case and other hemoglobin variants.

Results

Of the 1,158 neonates screened, 628 were boys (54.2%) and 530 were girls (45.8%). Sickle cell disease was found in 3 cases (0.2%) (95%C.I 0.12–0.28), sickle cell trait was found in 68 cases (5.8%) (95%C.I 4.5–7.5). After 6–9 mo of age three cases of sickle cell diseases were reinvestigated, out of which one case turned out to be double heterozygous for sickle cell and beta thalassemia trait. Fourteen preterm neonates reported as normal in initial screening were called for follow up after 6 mo of age, 10 infants reported in OPD and 4 lost in follow up. These 10 infants were reinvestigated; 2 had sickle cell disease, 1 had sickle cell trait and 7 infants were normal. Sixty eight cases of sickle cell trait found with initial screening were also called for follow up after 6 mo of age; 61 cases reported in OPD between 6 mo to 1 y of age and 7 cases lost in follow up. Sixty one infants were reinvestigated; 60 had sickle cell trait and 1 had sickle cell disease which was reported earlier as Sickle cell trait (FAS). Thus on total follow up of cases, there were 5(0.4%) sickle cell disease, 61(5.26%) sickle cell trait, 1(0.08%) double heterozygous for sickle cell and beta thalassemia trait which needs mutation studies for thalassemia characterization (s/β⁰ or s/β⁺).

Conclusions

Early detection of sickle cell disease (SS) done by neonatal screening will help in early prevention and management of complications in postnatal period.

     

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.     

Prenatal Diagnosis of Hemoglobinopathies in Turkey: Hacettepe Experience

Prenatal diagnosis of hemoglobinopathies was performed in 250 fetuses at risk for hemoglobinopathies. The main diagnostic procedures were in vitro hemoglobin synthesis analysis in fetal blood and analysis of DNA obtained from chorionic villus samples. Sixty-six percent of the fetuses were at risk for beta thalassemia major and 28% for sickle cell anemia. Beta thalassemia mutations were heterogenous, and 51 fetuses examined by the DNA technique were found to be at risk for at least 20 different combinations.     

Liver biopsy results in patients with sickle cell disease on chronic transfusions: poor correlation with ferritin levels

Background:

Chronic transfusions are effective in preventing stroke and other complications of sickle cell disease. The aim of this study was to determine whether serum ferritin levels correlated with liver iron content in sickle cell patients on chronic transfusion.

Procedure:

Forty‐four liver biopsy specimens from 38 patients with homozygous sickle cell anemia (HbSS) and one patient with sickle thalassemia receiving chronic transfusions were studied. Five patients underwent a second liver biopsy for follow up. Three ferritin measurements were used to calculate a mean for each patient. The association between serum ferritin levels and liver iron quantitation was measured using the Spearman rank correlation, and sensitivity and specificity were determined for selected threshold values of serum ferritin.

Results:

Serum ferritin levels ranged from 515 to 6076 ng/ml, liver iron concentration ranged from 1.8 to 67.97 mg/g dry weight. The amount of iron per gram liver dry weight was moderately correlated with serum ferritin values (r = 0.46). The correlation of duration of transfusion with serum ferritin (r = 0.40) and with liver iron content (r = 0.41) also indicated moderate correlation. Liver biopsy results led to changes in the management after 29/44 (66%) of the biopsies. Serum ferritin ≥2500 ng/ml predicted high liver iron content (≥7 mg/g), with a sensitivity of 62.5% and a specificity of 77.8%.

Conclusion:

We found a poor correlation between serum ferritin levels and liver iron content (LIC). Despite being on chelation therapy, many patients on chronic transfusion had high levels of liver iron. Measurement of LIC is highly recommended in these patients. Pediatr Blood Cancer 2008;50:62–65. © 2007 Wiley‐Liss, Inc.     

Prospective evaluation for respiratory pathogens in children with sickle cell disease and acute respiratory illness

Background

Human rhinovirus (HRV), human coronavirus (hCoV), human bocavirus (hBoV), and human metapneumovirus (hMPV) infections in children with sickle cell disease have not been well studied.

Procedure

Nasopharyngeal wash specimens were prospectively collected from 60 children with sickle cell disease and acute respiratory illness, over a 1‐year period. Samples were tested with multiplexed‐PCR, using an automated system for nine respiratory viruses, Chlamydophila pneumoniae, Mycoplasma pneumoniae, and Bordetella pertussis. Clinical characteristics and distribution of respiratory viruses in patients with and without acute chest syndrome (ACS) were evaluated.

Results

A respiratory virus was detected in 47 (78%) patients. Nine (15%) patients had ACS; a respiratory virus was detected in all of them. The demographic characteristics of patients with and without ACS were similar. HRV was the most common virus, detected in 29 of 47 (62%) patients. Logistic regression showed no association between ACS and detection of HRV, hCoV, hBoV, hMPV, and other respiratory pathogens. Co‐infection with at least one additional respiratory virus was seen in 14 (30%) infected patients, and was not significantly higher in patients with ACS (P = 0.10). Co‐infections with more than two respiratory viruses were seen in seven patients, all in patients without ACS. Bacterial pathogens were not detected.

Conclusion

HRV was the most common virus detected in children with sickle cell disease and acute respiratory illness, and was not associated with increased morbidity. Larger prospective studies with asymptomatic controls are needed to study the association of these emerging respiratory viruses with ACS in children with sickle cell disease. Pediatr Blood Cancer 2014;61:507–511. © 2013 Wiley Periodicals, Inc.

     

Arterial spin-labeled perfusion combined with segmentation techniques to evaluate cerebral blood flow in white and gray matter of children with sickle cell anemia

Background

Changes in cerebral perfusion are an important feature of the pathophysiology of sickle cell anemia (SCA); cerebrovascular ischemia occurs frequently and leads to neurocognitive deficits, silent infarcts, and overt stroke. Non‐invasive MRI methods to measure cerebral blood flow (CBF) by arterial spin labeling (ASL) afford new opportunities to characterize disease‐ and therapy‐induced changes in cerebral hemodynamics in patients with SCA. Recent studies have documented elevated gray matter (GM) CBF in untreated children with SCA, but no measurements of white matter (WM) CBF have been reported.

Procedures

Pulsed ASL with automated brain image segmentation‐classification techniques were used to determine the CBF in GM, WM, and abnormal white matter (ABWM) of 21 children with SCA, 18 of whom were receiving hydroxyurea therapy.

Results

GM and WM CBF were highly associated (R² = 0.76, P < 0.0001) and the GM to WM CBF ratio was 1.6 (95% confidence interval: 1.43–1.83). Global GM CBF in our treated cohort was 87 ± 24 mL/min/100 g, a value lower than previously reported in untreated patients with SCA. CBF was elevated in normal appearing WM (43 ± 14 mL/min/100 g) but decreased in ABWM (6 ± 12 mL/min/100 g), compared to published normal pediatric controls. Hemispheric asymmetry in CBF was noted in most patients.

Conclusions

These perfusion measurements suggest that hydroxyurea may normalize GM CBF in children with SCA, but altered perfusion in WM may persist. This novel combined approach for CBF quantification will facilitate prospective studies of cerebral vasculopathy in SCA, particularly regarding the effects of treatments such as hydroxyurea. Pediatr Blood Cancer 2009;52:85–91. © 2008 Wiley‐Liss, Inc.     

Red cell exchange does not appear to increase the rate of allo- and auto-immunization in chronically transfused children with sickle cell disease

Background

Allo‐ and auto‐antibody development is a well recognized complication of chronic red cell transfusion (RCT) in sickle cell disease (SCD). Limited matching of Rh (C, c, D, E, e) and K red cell antigens reduces the incidence of immunization.

Procedure

We reviewed our experience with red cell allo‐ and auto‐immunization in pediatric SCD patients receiving chronic and/or exchange transfusions, to evaluate the rate of immunization after limited red cell antigen matching and specifically during red cell exchange (RCE) transfusion. A retrospective chart review of the patients with SCD followed at our center between 2002 and 2006, who were started on chronic RCT before or during that time period, was conducted.

Results

Of the 93 patients who met study criteria, 23 (24%) developed antibodies during chronic red cell transfusions. Thirty‐four antibodies (15 auto‐antibodies, 18 allo‐antibodies) developed after the institution of limited red cell antigen matching. The rate of allo‐ and auto‐immunization per unit of red cell exposure after limited phenotyping was 1.5%, comparable to other published data. Fifteen patients underwent RCE, utilizing a total of 2,289 packed red cell units. None developed antibodies during RCE.

Conclusion

We conclude that limited red cell antigen matching is an effective strategy for reducing the incidence of allo‐ and auto‐immunization in chronically transfused children with SCD. RCE does not appear to increase the risk of allo‐ or auto‐immunization, despite exposure to more red cell units. Pediatr Blood Cancer 2011; 57: 294–296. © 2011 Wiley‐Liss, Inc.     

Neurocognitive deficits in children with sickle cell disease: a comprehensive profile

Background

Sickle cell disease (SCD) can lead to profound cerebral damage, associated with neurocognitive deficits. The aim of the current study was to evaluate a broad range of neurocognitive functions in children with SCD compared to a SES‐matched control group, in order to gain more insight into the specific deficits of these patients.

Methods

Forty‐one children with homozygous SCD (HbSS or HbS‐β0‐thalassemia) and 38 controls were assessed on a comprehensive set of well‐defined and validated measures of neurocognitive functioning. Besides general intelligence, we evaluated executive functioning extensively (including response inhibition, sustained attention, planning, visuo‐spatial working memory, and verbal working memory) as well as visuo‐motor functioning.

Results

SCD was clearly associated with lower IQ scores. More than one in three children with SCD had a Full‐scale IQ below 75. Furthermore, children with SCD showed deficits in visuo‐motor functioning. Some evidence was found for executive dysfunction: Children with SCD displayed poor visuo‐spatial working memory, as well as subtle deficits in sustained attention and planning. No significant differences were found between children with SCD and controls in terms of response inhibition and verbal working memory.

Conclusions

Children with SCD are at increased risk of lower intelligence, visuo‐motor impairments, and executive dysfunction. These neurocognitive deficits may underlie high rates of scholastic impairments in these children. The present findings further illuminate the importance of regular neurocognitive evaluations and future neurocognitive rehabilitation programs for children with SCD. Pediatr Blood Cancer 2011;56:783–788. © 2010 Wiley‐Liss, Inc.     

Lack of mortality in 22 children with sickle cell anemia and severe malarial anemia

Retrospective studies suggest that there is high mortality in children with sickle cell anemia (SCA) and severe malaria. We assessed mortality in Ugandan children with severe malarial anemia (SMA, n = 232) or cerebral malaria (CM, n = 267) by sickle cell hemoglobin genotype. Admission and 2‐year follow‐up mortality did not differ among children with SMA who had homozygous form of sickle cell hemoglobin (HbSS) versus normal form of adult hemoglobin (admission, 0/22, 0%, vs. 1/208, 0.5%; follow‐up, 1/22, 4.5%; 7/207, 3.4%, respectively; all P > 0.6). The single child with CM and HbSS survived. The study findings highlight the need for large prospective studies of malaria‐related mortality in children with SCA.     

Prevalence of low bone mass among adolescents with nontransfusion‐dependent hemoglobin E/β‐thalassemia and its relationship with anemia severity

1 Background

Low bone mass is common among adolescents with transfusion‐dependent β‐thalassemia despite adequate transfusion and iron chelation. However, there are few reports regarding bone mineral density (BMD) among adolescents with nontransfusion‐dependent thalassemia (NTDT). Indeed, only BMD data in patients with nontransfusion‐dependent (NTD) β‐thalassemia intermedia have been reported. No previous study has investigated BMD among adolescents with NTD hemoglobin (Hb) E/β‐thalassemia.

2 Objective

To determine the prevalence of low bone mass among adolescents with NTD Hb E/β‐thalassemia and factors relating to low bone mass.

3 Methods

We investigated BMD of lumbar spine (L2–L4; BMDLS) and total body (BMDTB), as measured by dual‐energy X‐ray absorptiometry, in 22 adolescents (aged 13.2–20 years) with NTD Hb E/β‐thalassemia.

4 Results

Low bone mass was found to be 18.2% and 22.7% at the lumbar spine (BMDLS Z‐score adjusted for bone age and height age) and 13.6% and 9.1% at the total body (BMDTB Z‐score adjusted for bone age and height age). Patients with mean Hb level <8 g/dl were more likely to have low bone mass (BMDLS and BMDTB Z‐scores adjusted for bone age) compared to those with Hb level ≥ 8 g/dl. Mean Hb level correlated with BMDLS and BMDTB Z‐scores adjusted for bone age.

5 Conclusion

We demonstrated that a low Hb level was associated with low bone mass among adolescents with NTD Hb E/β‐thalassemia. A significant proportion of low bone mass among these patients highlights the importance of appropriate management, including red cell transfusion, vitamin D and calcium supplementation for improved long‐term bone health.     

Elevated tricuspid regurgitation velocity in congenital hemolytic anemias: Prevalence and laboratory correlates

Elevated tricuspid valve regurgitation jet velocity (TRV ≥ 2.5 m/s) is associated with mortality among adults with sickle cell disease (SCD), but correlative biomarkers are not studied according to treatment exposure or genotypes. To investigate the associations between biomarkers and TRV elevation, we examined the relationship between TRV and hemolytic, inflammatory, and cardiac biomarkers, stratified by disease‐modifying treatments and SCD genotype. In total, 294 participants with SCD (mean age, 11.0 ± 3.7 years) and 49 hereditary spherocytosis (HS; mean age, 22.9 ± 19.75 years) were included for comparison and enrolled. TRV was elevated in 30.7% of children with SCD overall: 18.8% in HbSC/HbSβ⁺‐thalassemia, 28.9% in untreated HbSS/HbSβ⁰‐thalassemia, 34.2% in HbSS/HbSβ⁰‐thalassemia hydroxyurea‐treated, and 57% in HbSS/HbSβ⁰‐thalassemia chronic transfusion treated. TRV was elevated in 10.7% and 27.8% in HS children and adults, respectively. In children with SCD, elevated TRV was correlated with hemoglobin (odds ratio [OR] = 0.78, P = 0.004), lactate dehydrogenase (LDH; OR = 2.52, P = 0.005), and N‐terminal pro‐brain natriuretic peptide (NT‐pro BNP; OR = 1.003, P = 0.004). In multivariable logistic regression, adjusting for genotype, sex, hemolytic index, and treatment, hemoglobin concentration remained the only significant variable associated with elevated TRV in untreated HbSS/HbSβ⁰‐thalassemia participants. TRV was not associated with inflammatory markers, other markers of hemolysis, or NT‐pro BNP in untreated HbSS/HbSβ⁰‐thalassemia. Neither hemoglobin nor LDH was associated with TRV in HbSC/HbSβ⁺‐thalassemia. These results suggest that elevated TRV is influenced by the degree of anemia, possibly reflecting sickling as part of the disease pathophysiology. Prospective studies should monitor hemoglobin concentration as children with SCD age into adulthood, prompting initiation of TRV screening and monitoring.     

Multi-modal intervention for the inpatient management of sickle cell pain significantly decreases the rate of acute chest syndrome

Introduction

Pain in children with sickle cell disease (SCD) is the leading cause of acute care visits and hospitalizations. Pain episodes are a risk factor for the development of acute chest syndrome (ACS), contributing to morbidity and mortality in SCD. Few strategies exist to prevent this complication.

Methods

We performed a before‐and‐after prospective multi‐modal intervention. All children with SCD admitted for pain during the 2‐year study period were eligible. The multi‐modal intervention included standardized admission orders, monthly house staff education, and one‐on‐one patient and caregiver education.

Results

A total of 332 admissions for pain occurred during the study period; 159 before the intervention and 173 during the intervention. The ACS rate declined by 50% during the intervention period 25% (39 of 159) to 12% (21 of 173); P = 0.003. Time to ACS development increased from 0.8 days (0.03–5.2) to 1.7 days (0.03–5.8); P = 0.047. No significant difference was found in patient demographics, intravenous fluid amount administered, frequency of normal saline bolus administration, or cumulative opioid amount delivered in the first 24 hr. Patient controlled analgesia‐use was more common after the intervention 52% (82 of 159) versus 73% (126 of 173; P = 0.0001) and fewer patients required changes in analgesic dosing within the first 24 hr after admission (26%, 42 of 159 vs. 16%, 28 of 173; P = 0.015).

Conclusions

A multi‐modal intervention to educate and subsequently change physician's behavior likely decreased the rate of ACS in the setting of a single teaching hospital. Pediatr Blood Cancer 2011;56:262–266. © 2010 Wiley‐Liss, Inc.     

The burden and consequences of inherited blood disorders among young children in western Kenya

Although inherited blood disorders are common among children in many parts of Africa, limited data are available about their prevalence or contribution to childhood anaemia. We conducted a cross‐sectional survey of 858 children aged 6–35 months who were randomly selected from 60 villages in western Kenya. Haemoglobin (Hb), ferritin, malaria, C‐reactive protein (CRP) and retinol binding protein (RBP) were measured from capillary blood. Using polymerase chain reaction (PCR), Hb type, ?3.7 kb alpha‐globin chain deletion, glucose‐6‐phosphate dehydrogenase (G6PD) genotype and haptoglobin (Hp) genotype were determined. More than 2 out of 3 children had at least one measured blood disorder. Sickle cell trait (HbAS) and disease (HbSS) were found in 17.1% and 1.6% of children, respectively; 38.5% were heterozygotes and 9.6% were homozygotes for α⁺‐thalassaemia. The Hp 2‐2 genotype was found in 20.4% of children, whereas 8.2% of males and 6.8% of children overall had G6PD deficiency. There were no significant differences in the distribution of malaria by the measured blood disorders, except among males with G6PD deficiency who had a lower prevalence of clinical malaria than males of normal G6PD genotype (P = 0.005). After excluding children with malaria parasitaemia, inflammation (CRP > 5 mg L^?1), iron deficiency (ferritin < 12 μg L^?1) or vitamin A deficiency (RBP < 0.7 μg L^?1), the prevalence of anaemia among those without α⁺‐thalassaemia (43.0%) remained significantly lower than that among children who were either heterozygotes (53.5%) or homozygotes (67.7%, P = 0.03). Inherited blood disorders are common among pre‐school children in western Kenya and are important contributors to anaemia.     

Health-related Quality of Life in Children and Adolescents With Sickle Cell Disease

Objective

To assess health-related quality of life (HRQOL) in children and adolescents with sickle cell disease (SCD).

Design, Setting, and Participants

The PedsQL 4.0 Generic Scales, a multidimensional self-report instrument that has been shown to be valid and reliable for use in children and adolescents with chronic illness, consists of 23 items that assess physical, emotional, social, and school functioning. Questionnaires were administered to 124 children and adolescents (ages 8 to 18 years, child self-report) with SCD (100 sickle cell anemia, 24 sickle β zero thalassemia) and their parents (parent-proxy report). Summary scores for children's and parents' ratings of overall HRQOL and psychosocial health and subscale scores for physical, emotional, social, and school functioning were compared with published data for healthy children. Both summary and subscale scores for children with SCD also were compared with those of their parents.

Results

Children with SCD and their parents rated overall HRQOL and all subdomains of HRQOL lower than did healthy children and their parents (P < .001). Children with SCD rated their own HRQOL significantly better than their parents did for overall HRQOL and all subdomains (P < .001) except emotional functioning (P = .06).

Conclusions

Children with SCD and their parents perceived overall HRQOL and all HRQOL subdomains to be lower than scores reported in healthy children. Therefore, successful therapeutic efforts to improve HRQOL could represent important advances in the health of children with SCD.     

Dissatisfaction with hospital care for children with sickle cell disease not due only to race and chronic disease

Background

A previous study reported increased dissatisfaction with hospital care for children with sickle cell disease (SCD); however, its small size excluded determining whether race and chronic disease explained the difference.

Procedure

At hospital discharge, parents of children with SCD completed a survey assessing satisfaction with their child's hospital care. Results were compared to three years of satisfaction surveys for children with asthma or admitted to a general pediatrician's service collected as quality improvement for the hospital. The primary outcome was parent reported dissatisfaction with care. A chi‐square was used to compare dissatisfaction between SCD and each comparison group.

Results

Parents of 639 children were included, 34 children with SCD, 124 with asthma, and 481 general pediatric patients. Parents of children with SCD were more often dissatisfied with their child's care compared to children with asthma (32.4% vs. 16.9%, P < 0.05) and general pediatric patients (32.4% vs. 14.6%, P < 0.05). Among all children, dissatisfaction was higher in families with minority children (21.1% vs. 12.6%); this difference did not exist among children with asthma. Among African‐American children, a higher proportion of parents of children with SCD believed their child was treated differently because of race than children with asthma (45.5% vs. 2.8%, P < 0.01) or general pediatric patients (45.5% vs. 8.3%, P < 0.01).

Conclusion

Parents of children with SCD report increased dissatisfaction with care. While dissatisfaction was higher in minority families, the high rate of parental concern about race as a reason for families of children with SCD is not seen in African‐American families of children with asthma. Pediatr Blood Cancer 2009;53:174–178. © 2009 Wiley‐Liss, Inc.     

ELEVATED EXHALED CARBON MONOXIDE CONCENTRATION IN HEMOGLOBINOPATHIES AND ITS RELATION TO RED BLOOD CELL TRANSFUSION THERAPY

In this study, the authors examined a possible role of measurements of end-tidal carbon monoxide (CO), corrected for inhaled CO (ETCOc), as a noninvasive screening tool for hemoglobinopathies and as an indicator for when transfusions would be required in patients receiving chronic transfusions. ETCOc measurements were obtained in subjects with sickle cell disease (n = 18), thalassemia (n = 21), and healthy controls (n = 62). ETCOc values less than 3 parts per million (ppm) yielded a positive predictive value of 93% and negative predictive value of 94% in identifying hemoglobinopathies. Subsequently, 7 subjects with thalassemia had laboratory parameters and ETCOc measured over 2 transfusion cycles. ETCOc values were 4.90 ± 0.32 ppm (mean ± SD), with 89% of values being above normal (≥3 ppm). Pretransfusion ETCOc levels significantly correlated with pretransfusion reticulocyte count (r = .96, P <.001), but not with pretransfusion hemoglobin (r = .44, P = .16) or pretransfusion soluble transferrin receptors (sTfR, r = .52, P = .10). In conclusion, we found that patients with hemoglobinopathies have ETCOc values above the range for healthy controls and ETCOc measurements can be used as an adjunct to hemoglobin measurements to determine the proper timing of transfusions.