Mindray Pediatric Hematology Reference Intervals Study

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

This study is a collaborative initiative between the CALIPER (Canadian Laboratory Initiative on Pediatric Reference Intervals) program at the Hospital for Sick Children (HSC) and Mindray Medical International Limited to establish a database of pediatric reference intervals for hematology parameters on BC-6800Plus.

Study Overview

• Status: Completed
• Conditions: Establish Hematology Reference Intervals
• Intervention / Treatment: Diagnostic test: Hematology Parameters

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'

• Study Type: Observational
• Enrollment (Actual): 691

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G1X8
      • The Hospital for Sick Children

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Healthy community children and adolescents as well as healthy children and adolescents recruited from outpatient clinics at the Hospital for Sick Children.

Description

Inclusion Criteria:

• 0-<19 years

Exclusion Criteria:

• History of chronic illness
• Use of prescription medications within 2 weeks of collection
• Acute illness within 7 days of collection
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Healthy CALIPER Participants; Healthy community children and adolescents recruited through the CALIPER initiative as well as healthy children and adolescents recruited from outpatient clinics at the Hospital for Sick Children through the CALIPER initiative. Blood samples from these participants will be tested on the Mindray BC-6800Plus device to measure hematology parameters and establish reference intervals.

Diagnostic test: Hematology Parameters; Measurement of hematology parameters on BC-6800Plus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
White Blood Cell count	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Basophil number	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Basophil percentage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Neutrophil number	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Neutrophil percentage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Eosinophil number	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Eosinophil percentage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Lymphocyte number	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Lymphocyte percentage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Monocyte number	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Monocyte percentage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Immature Granulocyte number	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Immature Granulocyte percentage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Reticulocyte percentage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Reticulocyte number	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Reticulocyte Hemoglobin Expression	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Immature reticulocyte fraction	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Low fluorescent ratio	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Middle fluorescent ratio	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
High fluorescent ratio	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Red blood cell count	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Hemoglobin Concentration	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Mean Corpuscular Volume	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Mean Corpuscular Hemoglobin	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Mean Corpuscular Hemoglobin Concentration	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Red Blood Cell Distribution Width - Coefficient of Variation	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Red Blood Cell Distribution Width - Standard Deviation	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Hematocrit	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Nucleated red blood cell (NRBC) number	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Nucleated red blood cell percentage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Platelet count	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Mean Platelet Volume	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Platelet Distribution Width	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Plateletcrit	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Immature Platelet Fraction	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Platelet-large cell ratio	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Platelet-large cell count	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
High fluorescent Cell number	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
High fluorescent Cell percentage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Optical Red Blood Cell count	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Optical Platelet count	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Platelet count - Impedance	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Optical White Blood Cell count	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
White blood cell counts - Differential (DIFF)	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Total nucleated cell counts - DIFF	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Immature Eosinophil percentage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Immature Eosinophil number	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
High forward scatter NRBC ratio	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Low forward scatter NRBC ratio	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Neutrophil-to-lymphocyte ratio	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Platelet-to-lymphocyte ratio	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
White blood cell count - white cell nucleated basophil channel (WNB)	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Total nucleated cell counts	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Infected Red Blood Cell count	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Infected Red Blood Cell permillage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Microcyte count	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Microcyte percentage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Macrocyte count	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Macrocyte percentage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Mean Reticulocyte Volume	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Red Blood Cell Fragment Count	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Red Blood Cell Fragment Percentage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Platelet Distribution Width Standard Deviation	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Reticulocyte Production Index	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
High fluorescent Immature Platelet Fraction	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Immature Platelet Count	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
DIFF scattergram, mean neutrophil distribution-side scatter intensity	Scattergram of laboratory values derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
DIFF scattergram, mean neutrophil distribution-side fluorescent light intensity	Scattergram of laboratory values derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
DIFF scattergram, mean neutrophil distribution-forward scatter intensity	Scattergram of laboratory values derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
DIFF scattergram, mean lymphocyte distribution-side scatter intensity	Scattergram of laboratory values derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
DIFF scattergram, mean lymphocyte distribution-side fluorescent intensity	Scattergram of laboratory values derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
DIFF scattergram, mean lymphocyte distribution-forward scatter intensity	Scattergram of laboratory values derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
DIFF scattergram, mean monocyte distribution-side scatter intensity	Scattergram of laboratory values derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
DIFF scattergram, mean monocyte distribution-side fluorescent light intensity	Scattergram of laboratory values derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
DIFF scattergram, mean monocyte distribution-forward scatter intensity	Scattergram of laboratory values derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Dimorphic population, smaller distribution RBC count	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Dimorphic population, larger distribution RBC count	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Dimorphic population, smaller distribution mean corpuscular volume	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Dimorphic population, larger distribution mean corpuscular volume	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Mean Corpuscular Hemoglobin of Reticulocyte	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Mean Hemoglobin Distribution Width of Red Blood Cell	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Mean Platelet Concentration	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Mean Platelet Matter Content	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Hyperchromic Red Blood Cell percentage (Hyper%)	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection
Hypochromic Red Blood Cell percentage	Laboratory value derived from the Mindray BC-6800Plus Auto Hematology Analyzer	Within 8 hours of sample collection

Collaborators and Investigators

• Sponsor: The Hospital for Sick Children
• Collaborators: MINDRAY
• Investigators: Principal Investigator: Khosrow Khosrow, PhD, The Hospital for Sick Children

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2021
• Primary Completion (Actual): January 28, 2022
• Study Completion (Actual): February 11, 2022

Study Registration Dates

• First Submitted: February 8, 2021
• First Submitted That Met QC Criteria: February 12, 2021
• First Posted (Actual): February 17, 2021

Study Record Updates

• Last Update Posted (Actual): March 10, 2022
• Last Update Submitted That Met QC Criteria: March 8, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: REB1000069402

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

IPD Plan Description

Summary collated and anonymized data for each test available on the BC-6800Plus platform will be presented in the form of:

• Scatter plots of anonymized test results plotted by age and colour-coded by sex.
• Tables of established reference intervals, partitioned by age, sex, and ethnicity, if applicable.

To ensure that the knowledge gained from this study will be disseminated and available to all pediatric healthcare centres, laboratories, and pediatrician offices, our knowledge translation strategies include:

• Submission of data for publication to a peer-reviewed journal.
• Full data will be made available electronically via an online secure database on the CALIPER website and mobile app to facilitate access for the pediatric healthcare community internationally.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No