Establishment of Pediatric Reference Intervals for Mindray Hematology Parameters for Worldwide Application in Clinical Laboratories

Brief Summary

Detailed Description

The purpose of this study is to establish accurate and robust ethnic-, age- and sex-specific reference intervals for hematology parameters during childhood and adolescence on the Mindray analyzer (BC-6800Plus). Subjects will be recruited for this study through the CALIPER initiative and will include healthy children and adolescents in the community and in outpatient clinics at the Hospital for Sick Children (HSC). Since all participants will be recruited through the CALIPER initiative, the CALIPER consent forms will be used to obtain consent from each child and their parent/guardian. These forms obtain consent to use the samples to develop reference intervals for a range of tests. This study aims to measure hematology parameters in these samples and is therefore encompassed within the CALIPER consent. Recruitment will focus on subjects from three ethnic groups: Caucasians, Hispanics, and South Asians. A total of 960 subjects will be recruited for this study through the CALIPER initiative. The total sample size was determined by considering the requirement of 60-120 samples per partition for five age groups (0-\<1 years, 1-\<5 years, 5-\<10 years, 10-\<15 years, 15-\<19 years). Each age group will consist of an equal number of females and males. Additional samples may be required if data analysis suggests further age and/or sex partitioning for specific parameters. Each subject will provide a blood sample, which will be collected through the CALIPER initiative. These samples will be analyzed as part of this study in a secondary-use/retrospective fashion. Specifically, fresh whole blood specimens will be collected in K2EDTA tubes, placed in biohazard bags, stored on ice, and analyzed on the Mindray hematology platform within 8 hours of collection. All available hematology parameters for the BC-6800Plus will be measured (37 report and 48 research hematology parameters, as per the user manual). All procedures will be performed according to the user manual. Mindray quality control materials will be used to monitor the performance of the assays during the study. HSC will retain all quality controls data, maintenance record and reagents/calibrators lot numbers. Quality controls will be run daily and analysis of the CALIPER samples will proceed only after all the quality control (QC) data are acceptable. Data analysis will be performed by the CALIPER team in accordance with Clinical \& Laboratory Standards Institute (CLSI) EP28-A3c guidelines on defining, establishing, and verifying reference intervals in the clinical laboratory. The statistical approach for reference interval establishment has been described in-depth previously. In brief, analyte concentrations will be plotted against age and colour-coded by sex. Following visual inspection, extreme outliers will be removed and suspected age- and sex-specific partitions will be confirmed using the Harris and Boyd statistical method. Normality of data will be qualitatively assessed using quantile-quantile plots and quantitatively assessed using the Shapiro-Wilk's test. If skewed, the Box-Cox transformation will be applied in an effort to transform the data to a normal distribution. Outliers will be subsequently identified and removed using the Tukey or adjusted Tukey method for Gaussian and non-Gaussian data distributions, respectively. Reference intervals for partitions with ≥120 participants will be calculated using the nonparametric method. Reference intervals for partitions with ≥40 and \<120 participants (60 for group 0-\<1 years and 1-\<5 years, 120 for group 5-\<10 years, 10-\<15 years and 15-\<19 years) will be calculated using the robust method. 90% percent confidence intervals will also be calculated for the lower and upper limit of each reference interval. Ethnic-specific reference intervals will be calculated if sample size for each ethnic group is adequate. Otherwise, reference value distributions for South Asian and Hispanic children will be compared to those of Caucasian children. Oversight Authority (additional information) * This study is regulated by 'Canada: Health Canada' * This study has been reviewed and approved by 'Canada: Ethics Review Committee'

Primary Outcomes

Secondary Outcomes

• High fluorescent Cell percentage(Within 8 hours of sample collection)
• Immature Eosinophil percentage(Within 8 hours of sample collection)
• High forward scatter NRBC ratio(Within 8 hours of sample collection)
• Platelet-to-lymphocyte ratio(Within 8 hours of sample collection)
• Macrocyte percentage(Within 8 hours of sample collection)
• Optical White Blood Cell count(Within 8 hours of sample collection)
• Total nucleated cell counts - DIFF(Within 8 hours of sample collection)
• Low forward scatter NRBC ratio(Within 8 hours of sample collection)
• Reticulocyte Production Index(Within 8 hours of sample collection)
• High fluorescent Cell number(Within 8 hours of sample collection)
• Optical Red Blood Cell count(Within 8 hours of sample collection)
• White blood cell counts - Differential (DIFF)(Within 8 hours of sample collection)
• Immature Eosinophil number(Within 8 hours of sample collection)
• Microcyte count(Within 8 hours of sample collection)
• Microcyte percentage(Within 8 hours of sample collection)
• Platelet Distribution Width Standard Deviation(Within 8 hours of sample collection)
• Immature Platelet Count(Within 8 hours of sample collection)
• DIFF scattergram, mean neutrophil distribution-side scatter intensity(Within 8 hours of sample collection)
• DIFF scattergram, mean lymphocyte distribution-side scatter intensity(Within 8 hours of sample collection)
• Mean Hemoglobin Distribution Width of Red Blood Cell(Within 8 hours of sample collection)
• Infected Red Blood Cell permillage(Within 8 hours of sample collection)
• Optical Platelet count(Within 8 hours of sample collection)
• Platelet count - Impedance(Within 8 hours of sample collection)
• Neutrophil-to-lymphocyte ratio(Within 8 hours of sample collection)
• Total nucleated cell counts(Within 8 hours of sample collection)
• Infected Red Blood Cell count(Within 8 hours of sample collection)
• Mean Reticulocyte Volume(Within 8 hours of sample collection)
• Red Blood Cell Fragment Count(Within 8 hours of sample collection)
• High fluorescent Immature Platelet Fraction(Within 8 hours of sample collection)
• Dimorphic population, larger distribution RBC count(Within 8 hours of sample collection)
• White blood cell count - white cell nucleated basophil channel (WNB)(Within 8 hours of sample collection)
• Macrocyte count(Within 8 hours of sample collection)
• Red Blood Cell Fragment Percentage(Within 8 hours of sample collection)
• DIFF scattergram, mean lymphocyte distribution-side fluorescent intensity(Within 8 hours of sample collection)
• DIFF scattergram, mean monocyte distribution-forward scatter intensity(Within 8 hours of sample collection)
• Dimorphic population, smaller distribution mean corpuscular volume(Within 8 hours of sample collection)
• Mean Corpuscular Hemoglobin of Reticulocyte(Within 8 hours of sample collection)
• Mean Platelet Concentration(Within 8 hours of sample collection)
• DIFF scattergram, mean neutrophil distribution-side fluorescent light intensity(Within 8 hours of sample collection)
• DIFF scattergram, mean lymphocyte distribution-forward scatter intensity(Within 8 hours of sample collection)
• Dimorphic population, smaller distribution RBC count(Within 8 hours of sample collection)
• Mean Platelet Matter Content(Within 8 hours of sample collection)
• Hypochromic Red Blood Cell percentage(Within 8 hours of sample collection)
• DIFF scattergram, mean neutrophil distribution-forward scatter intensity(Within 8 hours of sample collection)
• DIFF scattergram, mean monocyte distribution-side scatter intensity(Within 8 hours of sample collection)
• DIFF scattergram, mean monocyte distribution-side fluorescent light intensity(Within 8 hours of sample collection)
• Dimorphic population, larger distribution mean corpuscular volume(Within 8 hours of sample collection)
• Hyperchromic Red Blood Cell percentage (Hyper%)(Within 8 hours of sample collection)