The ektacytometric elongation Index (EI) of erythrocytes, validation of a prognostic, rheological biomarker for patients with sickle cell disease.

OBJECTIVES: Validation of the measurement of erythrocyte deformability as a useful prognostic, rheological biomarker for patients with sickle cell disease (SCD). METHODS: The degree of reduced deformability was based on the value of the maximum elongation index (EImax ) of the deformability curve of an osmotic gradient ektacytometer. The performance of this technique was analytically and clinically validated by analysing 200 normal subjects and 100 patients with well-documented thalassemia's and Hb variants in relation to their clinical condition. RESULTS: In this study, we show that EImax is a reproducible parameter with a small inter-individual coefficient of (Biological) variation (CV)=1.6% and a small intra-individual CV=3.5%. We demonstrate that loss of deformability correlates with the clinical condition and the various mutations underlying sickle cell disease and thalassemia. For SCD patients, a strongly reduced EImax with a cut-off =0.360 is a signal for future vaso-occlusive (VOC) events requiring hospitalisation with a specificity=85%, sensitivity=80%, PPV=81% and NPV=84% based on a ROC curve (AUC=0.89). CONCLUSION: This study validated the clinical utility of EImax as a prognostic marker for future clinical problems in individual high-risk SCD patients. In addition, EImax may help to achieve an adequate personal transfusion policy for an optimal blood flow in anaemic patients with SCD.

Serum hepcidin in infants born after 32 to 37 wk of gestational age.

BACKGROUND: Preterm infants are at risk of iron deficiency (ID). Hepcidin has been suggested as a good additional indicator of ID in preterm infants, next to ferritin. METHODS: In a prospective observational study, we analyzed serum hepcidin in 111 infants born after 32+0 to 36+6 wk gestational age during the first 4 mo of life. RESULTS: Hepcidin concentrations decreased during the first 4 mo of life, and concentrations were lower in infants with ID compared to those without ID. Infants who developed ID at the age of 4 mo had already significantly lower levels of hepcidin at 1.5 mo of age, while ferritin was already significantly lower at the age of 1 wk. CONCLUSION: Hepcidin concentrations of late preterm infants decrease during the first 4 mo of life. This decrease, which parallels a decrease of ferritin concentration, we interpret as a physiological response, aiming to increase iron availability. Hepcidin concentrations are lower in infants with ID compared with those without ID, with a notable change already observed at 1.5 mo of age. Hepcidin can be used as an early marker of ID, although an additive value of hepcidin over ferritin in the diagnosis of ID is not present.

Serum hepcidin measured by immunochemical and mass-spectrometric methods and their correlation with iron status indicators in healthy children aged 0.5-3 y.

BACKGROUND: The diagnostic use of hepcidin is limited by the absence of standardization and lack of age-specific reference ranges in children in particular. The aim of this study was to determine reference ranges of serum hepcidin in healthy children aged 0.5-3 y using mass spectometry (MS) and a commercial immunochemical (IC) assay, and to investigate its association with other indicators of iron status and inflammation. METHODS: We included 400 healthy children aged 0.5-3 y. We constructed reference ranges for MS-hepcidin and IC-hepcidin concentrations using the median, P2.5, and P97.5 in a normative population of 219 children with no anemia, no infection and/or inflammation, and no iron deficiency. RESULTS: Median concentrations (P2.5-P97.5) of MS-hepcidin and IC-hepcidin were 3.6 nmol/l (0.6-13.9 nmol/l) and 7.9 nmol/l (1.9-28.6 nmol/l), respectively. We found a good correlation between both methods. However, MS-hepcidin was consistently lower than IC-hepcidin. Hepcidin correlated with ferritin and C-reactive protein. CONCLUSION: We provide reference ranges for hepcidin for an MS and commercial IC method. Absolute values between assays differed significantly, but hepcidin concentrations obtained by MS and IC methods correlate with each other, and both correlate with ferritin and CRP.

The value of soluble transferrin receptor and hepcidin in the assessment of iron status in children with cystic fibrosis.

BACKGROUND: The value of ferritin in the diagnosis of iron deficiency is limited in patients with CF since it increases in the presence of inflammation. We hypothesized that the soluble transferrin receptor (sTfR) and hepcidin may provide more information than ferritin in assessing iron status in children with CF. METHODS: We analyzed sTfR and hepcidin in relation to conventional iron status indicators in 49 children with CF. RESULTS: We found no differences in sTfR concentration between children with and those without ID. sTfR concentrations were within the normal range in all children. Hepcidin concentrations were low, and concentrations below the limit of detection were observed in 25% of the clinically stable children. CONCLUSION: The sTfR is not useful to determine the iron status in this population, whereas hepcidin might serve as an early indicator of deficient iron stores in children with CF.

Prevalence and risk factors of iron deficiency in healthy young children in the southwestern Netherlands.

OBJECTIVES: Iron deficiency (ID) and iron deficiency anemia (IDA), during the first years of life, are associated with delayed motor and neurological development. Many studies evaluated iron status without an assessment of an acute-phase protein to identify infection. Because most indicators of iron status are influenced by infection, these data may underestimate the ID prevalence. A food consumption survey in the Netherlands showed that the mean iron intake of children ages 2 to 3 years was below the advised adequate intake of 7 mg/day. The aim of the study was to investigate iron status in a well-defined, healthy population of young children in the southwestern region of the Netherlands and to identify risk factors for ID. METHODS: We conducted a multicenter, observational study in healthy children ages 0.5 to 3 years. We defined ID as ferritin <12 µg/L and IDA when, in addition, hemoglobin was <110 g/L. Children with elevated C-reactive protein levels (>5 mg/L) or underlying causes for anemia were excluded. Parents filled in a questionnaire to identify risk factors for ID. RESULTS: We included 400 children in the study. ID and IDA were detected in 18.8% and 8.5% of the children, respectively. The present use of formula and the visit of preschool/day care were associated with a lower prevalence of ID, and a high intake of cow's milk was associated with a higher prevalence of ID, after adjustment for age. CONCLUSIONS: ID is present in 18.8% of healthy children ages 0.5 to 3 years and living in the southwestern region of the Netherlands. The present visit of preschool/day care and the use of formula are associated with a reduced risk of ID, whereas a high intake of cow's milk is associated with an increased risk of ID.

Feasibility of nonselective testing for hemoglobinopathies in early pregnancy in The Netherlands.

OBJECTIVE: To examine the feasibility of standardized hemoglobinopathy (HBP) carrier testing for pregnant women in The Netherlands in addition to the standard anemia screening. METHODS: We assessed the prevalence of HBP in women at the time of the first pregnancy visit using both a prospective cohort (N = 703) and a retrospective series of women selected at random (N = 588). For the purpose of analysis, the population was divided into a high risk and a low risk group for HBP based on maternal ethnicity. Screening for HBP utilized standard screening tests for anemia, with additional high performance liquid chromatography (Variant II); molecular analysis was performed by Gap-polymerase chain reaction (Gap-PCR) and if necessary, direct sequencing and multiplex ligation-dependent probe amplification (MLPA). Family history was reported or collected from the medical records. RESULTS: ß-Globin defects were found in 3.9% of the total population (50/1291). The frequency in the high risk population was 5.6% (37/656), compared with 1.2% (6/501) in the low risk group. In the prospective study we found 30 HBP carriers, leading to testing of 16 partners and identification of two couples at risk. One affected child was born. Mean gestational age at the screening was 11.3 weeks with a standard deviation (SD) of 5.8. CONCLUSION: We found that the prevalence of HBP carriers is high enough in our population to warrant HBP testing for the entire multiethnic population in early pregnancy at the time of anemia screening. This is feasible as most women had their booking early in their first trimester.