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Next-generation reference intervals for pediatric hematology

  • Jakob Zierk EMAIL logo , Johannes Hirschmann , Dennis Toddenroth , Farhad Arzideh , Rainer Haeckel , Alexander Bertram , Holger Cario , Michael C. Frühwald , Hans-Jürgen Groß , Arndt Groening , Stefanie Grützner , Thomas Gscheidmeier , Torsten Hoff , Reinhard Hoffmann , Rainer Klauke , Alexander Krebs , Ralf Lichtinghagen , Sabine Mühlenbrock-Lenter , Michael Neumann , Peter Nöllke , Charlotte M. Niemeyer , Oliver Razum , Hans-Georg Ruf , Udo Steigerwald , Thomas Streichert , Antje Torge , Wolfgang Rascher , Hans-Ulrich Prokosch , Manfred Rauh und Markus Metzler
Veröffentlicht/Copyright: 22. April 2019
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Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 57 Heft 10

Abstract

Background

Interpreting hematology analytes in children is challenging due to the extensive changes in hematopoiesis that accompany physiological development and lead to pronounced sex- and age-specific dynamics. Continuous percentile charts from birth to adulthood allow accurate consideration of these dynamics. However, the ethical and practical challenges unique to pediatric reference intervals have restricted the creation of such percentile charts, and limitations in current approaches to laboratory test result displays restrict their use when guiding clinical decisions.

Methods

We employed an improved data-driven approach to create percentile charts from laboratory data collected during patient care in 10 German centers (9,576,910 samples from 358,292 patients, 412,905–1,278,987 samples per analyte). We demonstrate visualization of hematology test results using percentile charts and z-scores (www.pedref.org/hematology) and assess the potential of percentiles and z-scores to support diagnosis of different hematological diseases.

Results

We created percentile charts for hemoglobin, hematocrit, red cell indices, red cell count, red cell distribution width, white cell count and platelet count in girls and boys from birth to 18 years of age. Comparison of pediatricians evaluating complex clinical scenarios using percentile charts versus conventional/tabular representations shows that percentile charts can enhance physician assessment in selected example cases. Age-specific percentiles and z-scores, compared with absolute test results, improve the identification of children with blood count abnormalities and the discrimination between different hematological diseases.

Conclusions

The provided reference intervals enable precise assessment of pediatric hematology test results. Representation of test results using percentiles and z-scores facilitates their interpretation and demonstrates the potential of digital approaches to improve clinical decision-making.

Keywords: hematology; laboratory test result display; pediatric reference intervals

Acknowledgments

We thank the members of the German Society for Clinical Chemistry and Laboratory Medicine’s working group on guide limits (“AG Richtwerte der DGKL”) for their valuable input.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: Supported by the Interdisciplinary Center for Clinical Research (IZKF) at the University Hospital of the University of Erlangen-Nuremberg.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Supplementary Material

The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2018-1236).

Article note:

Prior presentations: 22th Congress of the European Hematology Association (EHA), Madrid, Spain, June 2017 (abstract/e-poster); 14th Annual Congress of the German Society of Clinical Chemistry and Laboratory Medicine (DGKL), Oldenburg, Germany, October 2017 (talk and poster); XIVth International Congress of Paediatric Laboratory Medicine, Durban, South Africa October 2017 (talk and poster), IFCC WorldLab 2017, Durban, South Africa, October 2017 (poster); preliminary percentile charts have been published by the German Society for Paediatric Oncology and Haematology (GPOH) at www.kinderblutkrankheiten.de

Received: 2018-11-18
Accepted: 2019-03-02
Published Online: 2019-04-22
Published in Print: 2019-09-25

©2019 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Blood biomarkers in neurology: “a call to arms” for laboratory professionals
  4. Reviews
  5. Diagnostic accuracy of glycated hemoglobin for gestational diabetes mellitus: a systematic review and meta-analysis
  6. Laboratory medicine: health evaluation in elite athletes
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  15. Preanalytical robustness of blood collection tubes with RNA stabilizers
  16. Continual improvement of the pre-analytical process in a public health laboratory with quality indicators-based risk management
  17. Comparison of six commercial serum exosome isolation methods suitable for clinical laboratories. Effect in cytokine analysis
  18. A multicenter study to evaluate harmonization of assays for N-terminal propeptide of type I procollagen (PINP): a report from the IFCC-IOF Joint Committee for Bone Metabolism
  19. Correlations between serum and CSF pNfH levels in ALS, FTD and controls: a comparison of three analytical approaches
  20. Dynamics of extracellular matrix proteins in cerebrospinal fluid and serum and their relation to clinical outcome in human traumatic brain injury
  21. Free light chains in the cerebrospinal fluid. Comparison of different methods to determine intrathecal synthesis
  22. Reference Values and Biological Variations
  23. Reference interval by the indirect approach of serum thyrotropin (TSH) in a Mediterranean adult population and the association with age and gender
  24. Next-generation reference intervals for pediatric hematology
  25. Hematology and Coagulation
  26. Preliminary evaluation of a new flow cytometry method for the routine hematology workflow
  27. Diabetes
  28. Trueness assessment of HbA1c routine assays: are processed EQA materials up to the job?
  29. Infectious Diseases
  30. Utility of procalcitonin for differentiating cryptogenic organising pneumonia from community-acquired pneumonia
  31. A high C-reactive protein/procalcitonin ratio predicts Mycoplasma pneumoniae infection
  32. Letters to the Editor
  33. Evaluation of reference change values for a hs-cTnI immunoassay using both plasma samples of healthy subjects and patients and quality control samples
  34. Outlier removal methods for skewed data: impact on age-specific high-sensitive cardiac troponin T 99th percentiles
  35. Comparison of precision and operational performances across six immunochemistry analyzers
  36. Evaluation of the possible interference of abiraterone therapy on testosterone immunoassay
  37. Erroneous thyroid and steroid hormones profile due to anti-streptavidin antibodies
  38. Reference values for 24,25-dihydroxyvitamin D and the 25-hydroxyvitamin D/24,25-dihydroxyvitamin D ratio
  39. Pre-analytical error in a hematology laboratory: an avoidable cause of compromised quality in reporting
  40. Stability of tubular damage markers epidermal growth factor and heparin-binding EGF-like growth factor in urine
  41. Blood from heparin tubes is an acceptable alternative to assess hematocrit determination
https://doi.org/10.1515/cclm-2018-1236
Schlagwörter für diesen Artikel
hematology; laboratory test result display; pediatric reference intervals

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Blood biomarkers in neurology: “a call to arms” for laboratory professionals
  4. Reviews
  5. Diagnostic accuracy of glycated hemoglobin for gestational diabetes mellitus: a systematic review and meta-analysis
  6. Laboratory medicine: health evaluation in elite athletes
  7. Prostate cancer screening: guidelines review and laboratory issues
  8. Opinion Papers
  9. Extra-analytical sources of uncertainty: which ones really matter?
  10. Benefits and harms of wellness initiatives
  11. Genetics and Molecular Diagnostics
  12. Analytical and clinical validation of a novel amplicon-based NGS assay for the evaluation of circulating tumor DNA in metastatic colorectal cancer patients
  13. General Clinical Chemistry and Laboratory Medicine
  14. Pre-analytical practices for routine coagulation tests in European laboratories. A collaborative study from the European Organisation for External Quality Assurance Providers in Laboratory Medicine (EQALM)
  15. Preanalytical robustness of blood collection tubes with RNA stabilizers
  16. Continual improvement of the pre-analytical process in a public health laboratory with quality indicators-based risk management
  17. Comparison of six commercial serum exosome isolation methods suitable for clinical laboratories. Effect in cytokine analysis
  18. A multicenter study to evaluate harmonization of assays for N-terminal propeptide of type I procollagen (PINP): a report from the IFCC-IOF Joint Committee for Bone Metabolism
  19. Correlations between serum and CSF pNfH levels in ALS, FTD and controls: a comparison of three analytical approaches
  20. Dynamics of extracellular matrix proteins in cerebrospinal fluid and serum and their relation to clinical outcome in human traumatic brain injury
  21. Free light chains in the cerebrospinal fluid. Comparison of different methods to determine intrathecal synthesis
  22. Reference Values and Biological Variations
  23. Reference interval by the indirect approach of serum thyrotropin (TSH) in a Mediterranean adult population and the association with age and gender
  24. Next-generation reference intervals for pediatric hematology
  25. Hematology and Coagulation
  26. Preliminary evaluation of a new flow cytometry method for the routine hematology workflow
  27. Diabetes
  28. Trueness assessment of HbA1c routine assays: are processed EQA materials up to the job?
  29. Infectious Diseases
  30. Utility of procalcitonin for differentiating cryptogenic organising pneumonia from community-acquired pneumonia
  31. A high C-reactive protein/procalcitonin ratio predicts Mycoplasma pneumoniae infection
  32. Letters to the Editor
  33. Evaluation of reference change values for a hs-cTnI immunoassay using both plasma samples of healthy subjects and patients and quality control samples
  34. Outlier removal methods for skewed data: impact on age-specific high-sensitive cardiac troponin T 99th percentiles
  35. Comparison of precision and operational performances across six immunochemistry analyzers
  36. Evaluation of the possible interference of abiraterone therapy on testosterone immunoassay
  37. Erroneous thyroid and steroid hormones profile due to anti-streptavidin antibodies
  38. Reference values for 24,25-dihydroxyvitamin D and the 25-hydroxyvitamin D/24,25-dihydroxyvitamin D ratio
  39. Pre-analytical error in a hematology laboratory: an avoidable cause of compromised quality in reporting
  40. Stability of tubular damage markers epidermal growth factor and heparin-binding EGF-like growth factor in urine
  41. Blood from heparin tubes is an acceptable alternative to assess hematocrit determination
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