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Updated: Dec 12, 2025

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Complex biological patterns of hematology parameters in childhood necessitating age- and sex-specific reference
Mary Kathryn Bohn1,2, Victoria Higgins1,2, Houman Tahmasebi1
1CALIPER Program, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
Insights
This study provides essential age- and sex-specific reference intervals for 25 hematology parameters in children and adolescents. These findings address critical gaps in pediatric reference data, improving test result interpretation.
Area of Science:
- Pediatric Hematology
- Clinical Laboratory Science
- Biostatistics
Background:
- Hematology tests are vital in pediatric care but lack updated reference intervals.
- Physiological changes during growth and development complicate interpretation.
- Existing pediatric hematology reference intervals are insufficient for modern platforms.
Purpose of the Study:
- To establish comprehensive, age- and sex-specific reference intervals for 25 hematology parameters.
- To address critical gaps in pediatric reference data for healthy children and adolescents.
- To utilize the Sysmex XN-3000 analytical system for standardized measurements.
Main Methods:
- Analysis of 25 hematological parameters from 641 healthy pediatric participants (birth to <21 years).
- Utilized fresh whole blood samples with informed consent.
- Calculated age- and sex-specific reference standards following Clinical and Laboratory Standards Institute guidelines.
Main Results:
- Established reference intervals for 25 hematology analytes.
- 19 analytes required age-partitioning, and 7 required sex-partitioning.
- Observed significant age- and sex-specific differences, often linked to puberty onset.
Conclusions:
- A comprehensive database of pediatric hematology reference intervals was created using the CALIPER cohort and Sysmex XN-3000.
- Data demonstrate the dynamic nature of hematological profiles in children and adolescents.
- Emphasizes the necessity of stratifying reference intervals by age and sex for accurate interpretation.
Introduction:
Hematology laboratory parameters are among the most routinely ordered tests in support of adult and pediatric care. However, appropriate interpretation of test results has been a challenge in pediatrics since accurate and up-to-date reference intervals that reflect the dynamic physiological changes associated with growth and development have not been available. Critical gaps continue to exist in pediatric hematology reference intervals for modern laboratory platforms. To address this gap, this study establishes age- and sex-specific reference intervals for 25 hematology parameters in the CALIPER cohort of healthy children and adolescents using a common platform, the Sysmex XN-3000 analytical system.
Methods:
Fresh whole blood samples collected from a total of 641 healthy children and adolescents (birth to <21 years) with informed consent were analyzed for 25 hematological parameters on the Sysmex XN-3000 Hematology Analyzer. Age- and sex-specific reference standards were calculated based on Clinical and Laboratory Standards Institute guidelines.
Results:
Of the 25 analytes assessed, 19 required age-partitioning and seven required sex-partitioning (ie, red blood cell count, hemoglobin, hematocrit, mean corpuscular volume, red blood cell distribution width-SD, red blood cell distribution width-CV, and monocyte percentage). Age- and sex-specific differences mostly coincided with the onset of puberty.
Conclusion:
This study establishes a comprehensive database of pediatric reference intervals for hematology parameters in the CALIPER cohort using the widely used Sysmex XN-3000 analytical platform. These data highlight the dynamic hematological profile observed in healthy children and adolescents and the need for reference interval stratification by age and sex.
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