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Clin Chem Lab Med. 2019 Apr 22. pii: /j/cclm.ahead-of-print/cclm-2018-1236/cclm-2018-1236.xml. doi: 10.1515/cclm-2018-1236. [Epub ahead of print]

Next-generation reference intervals for pediatric hematology.

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Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Loschgestr. 15, 91054 Erlangen, Germany, Phone: +49 9131/85-33731, Fax: +49 9131/85-35742.
Chair of Medical Informatics, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
Department of Statistics, University of Bremen, Bremen, Germany.
Bremer Zentrum für Laboratoriumsmedizin, Klinikum Bremen Mitte, Bremen, Germany.
MVZ wagnerstibbe, amedes Gruppe, Hannover, Germany.
Department of Pediatrics and Adolescent Medicine, University Medical Center Ulm, Ulm, Germany.
Department of Pediatric Oncology/Hematology, Klinikum Augsburg, Augsburg, Germany.
Core Facility of Clinical Chemistry, University Medical Center Ulm, Ulm, Germany.
Department of Transfusion Medicine and Haemostasis, Klinikum Augsburg, Augsburg, Germany.
Central Laboratory, Gesundheit Nord - Bremen Hospital Group, Bremen, Germany.
Institute for Laboratory Medicine and Microbiology, Klinikum Augsburg, Augsburg, Germany.
Institute of Clinical Chemistry, Hannover Medical School, Hannover, Germany.
MVZ Labor PD Dr. Volkmann und Kollegen, Karlsruhe, Germany.
Division of Laboratory Medicine, University Hospital of Würzburg, Würzburg, Germany.
Division of Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany.
Department of Epidemiology & International Public Health, School of Public Health, Bielefeld University, Bielefeld, Germany.
Department of Clinical Chemistry, University Hospital of Cologne, Cologne, Germany.
Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.
Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Erlangen, Germany.


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 ( 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.


hematology; laboratory test result display; pediatric reference intervals


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