Next-generation reference intervals for pediatric hematology

Author:

Zierk Jakob1,Hirschmann Johannes2,Toddenroth Dennis2,Arzideh Farhad3,Haeckel Rainer4,Bertram Alexander5,Cario Holger6,Frühwald Michael C.7,Groß Hans-Jürgen8,Groening Arndt5,Grützner Stefanie9,Gscheidmeier Thomas8,Hoff Torsten10,Hoffmann Reinhard11,Klauke Rainer12,Krebs Alexander13,Lichtinghagen Ralf12,Mühlenbrock-Lenter Sabine10,Neumann Michael14,Nöllke Peter15,Niemeyer Charlotte M.15,Razum Oliver16,Ruf Hans-Georg11,Steigerwald Udo14,Streichert Thomas17,Torge Antje18,Rascher Wolfgang19,Prokosch Hans-Ulrich2,Rauh Manfred19,Metzler Markus19

Affiliation:

1. Department of Pediatrics and Adolescent Medicine , University Hospital Erlangen , Loschgestr. 15 , 91054 Erlangen , Germany , Phone: +49 9131/85-33731, Fax: +49 9131/85-35742

2. Chair of Medical Informatics , Friedrich-Alexander-University Erlangen-Nuremberg , Erlangen , Germany

3. Department of Statistics , University of Bremen , Bremen , Germany

4. Bremer Zentrum für Laboratoriumsmedizin , Klinikum Bremen Mitte , Bremen , Germany

5. MVZ wagnerstibbe, amedes Gruppe , Hannover , Germany

6. Department of Pediatrics and Adolescent Medicine , University Medical Center Ulm , Ulm , Germany

7. Department of Pediatric Oncology/Hematology , Klinikum Augsburg , Augsburg , Germany

8. Core Facility of Clinical Chemistry , University Medical Center Ulm , Ulm , Germany

9. Department of Transfusion Medicine and Haemostasis , Klinikum Augsburg , Augsburg , Germany

10. Central Laboratory , Gesundheit Nord – Bremen Hospital Group , Bremen , Germany

11. Institute for Laboratory Medicine and Microbiology , Klinikum Augsburg , Augsburg , Germany

12. Institute of Clinical Chemistry, Hannover Medical School , Hannover , Germany

13. MVZ Labor PD Dr. Volkmann und Kollegen , Karlsruhe , Germany

14. Division of Laboratory Medicine , University Hospital of Würzburg , Würzburg , Germany

15. Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine , University of Freiburg , Freiburg , Germany

16. Department of Epidemiology & International Public Health, School of Public Health , Bielefeld University , Bielefeld , Germany

17. Department of Clinical Chemistry , University Hospital of Cologne , Cologne , Germany

18. Institute of Clinical Chemistry , University Hospital Schleswig-Holstein, Campus Kiel , Kiel , Germany

19. Department of Pediatrics and Adolescent Medicine , University Hospital Erlangen , Erlangen , Germany

Abstract

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.

Publisher

Walter de Gruyter GmbH

Subject

Biochemistry, medical,Clinical Biochemistry,General Medicine

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