Complex Biological Profile of Hematologic Markers across Pediatric, Adult, and Geriatric Ages: Establishment of Robust Pediatric and Adult Reference Intervals on the Basis of the Canadian Health Measures Survey

Abstract

BACKGROUND In a collaboration between the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) and the Canadian Health Measures Survey (CHMS), we determined reference value distributions using an a priori approach and created a comprehensive database of age- and sex-stratified reference intervals for clinically relevant hematologic parameters in a large household population of children and adults. METHODS The CHMS collected data and blood samples from 11 999 respondents aged 3–79 years. Hematology markers were measured with either the Beckman Coulter HmX or Siemens Sysmex CA-500 Series analyzers. After applying exclusion criteria and removing outliers, we determined statistically relevant age and sex partitions and calculated reference intervals, including 90% CIs, according to CSLI C28-A3 guidelines. RESULTS Hematology marker values showed dynamic changes from childhood into adulthood as well as between sexes, necessitating distinct partitions throughout life. Most age partitions were necessary during childhood, reflecting the hematologic changes that occur during growth and development. Hemoglobin, red blood cell count, hematocrit, and indices (mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration) increased with age, but females had lower hemoglobin and hematocrit starting at puberty. Platelet count gradually decreased with age and required multiple sex partitions during adolescence and adulthood. White blood cell count remained relatively constant over life, whereas fibrinogen increased slightly, requiring distinct age and sex partitions. CONCLUSIONS The robust dataset generated in this study has allowed observation of dynamic biological profiles of several hematology markers and the establishment of comprehensive age- and sex-specific reference intervals that may contribute to accurate monitoring of pediatric, adult, and geriatric patients.

Recommendation for the review of biological reference intervals in medical laboratories

“…Adeli et al [21][22][23] conducted the study of the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) and the Canadian Health Measures Survey (CHMS) which was carried on well-defined populations according to a pre-analytical and analytical protocol tightly controlled. This multicenter study compared the references intervals between the key analytical systems.…”

Transference and Validation of Reference Intervals

“…Such is the case with the joint collaboration of the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) 4 and the Canadian Health Measures Survey (CHMS), which collected 11 999 biospecimens representative of 96% of Canada's household population covering the ages 3-79 years and supported by other physical measures and general health information (1 ). Before the calculation of intervals, subjects were first excluded according to various parameters including increased body mass index, history of chronic or metabolic disease, acute illness, or use of prescribed medication a month before sample collection.…”

“…Adeli and colleagues present data from the CHMS-CALIPER formal reference interval study in 3 separate articles in this issue of Clinical Chemistry (2)(3)(4) It is the responsibility of individual laboratories or laboratory networks to use reference intervals that are appropriate for their methodologies and the population they serve, as specified by International Organization for Standardization (ISO) standard 15189 (5 ). Advice on how to do this is found in guidelines from the CLSI.…”

The Power of Asterisks

“…In this issue of Clinical Chemistry, Adeli and colleagues provide, in a series of 3 papers (2)(3)(4), an exceptional compilation of high-quality reference interval data. Following a protocol they developed for the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) 2 (5 ), which was undertaken to address the dearth of pediatric reference interval data, they arranged for roughly 12 000 reference individuals to provide blood and urine samples to be analyzed for a large number of common laboratory tests.…”

“…Interestingly, there are profuse data on age and sex but no discussion of race or ethnicity, except in the third article (4 ), where the authors state that small sample sizes precluded analysis of the effects of these factors. This is unfortunate, because race and ethnicity can exert powerful effects on reference intervals.…”