Short Communication Clinical decision limits for interpretation of direct bilirubin — A CALIPER study of healthy multiethnic children and case report reviews Manjit S. Devgun a, ⁎, Man Khun Chan b , Adil M. El-Nujumi c , Rosemary Abara d , David Armbruster e , Khosrow Adeli b,f,1 a Clinical Laboratories, Department of Biochemistry, NHS Lanarkshire, Wishaw General Hospital, 50 Netherton Street, Wishaw ML2 0DP, Scotland, UK b Clinical Biochemistry Division, Department of Pediatric Laboratory Medicine, the Hospital for Sick Children, Toronto, Ontario, Canada c Department of Medicine and Gastroenterology, NHS Lanarkshire, Wishaw General Hospital, 50 Netherton Street, Wishaw ML2 0DP, Scotland, UK d Department of Paediatrics and Neonatology, NHS Lanarkshire, Wishaw General Hospital, 50 Netherton Street, Wishaw ML2 0DP, Scotland, UK e Abbott Diagnostics, Abbott Park, IL, USA f Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada abstract article info Article history: Received 16 June 2014 Received in revised form 29 October 2014 Accepted 30 October 2014 Available online 7 November 2014 Keywords: Direct bilirubin Conjugated bilirubin Reference interval Clinical decision limit Hyperbilirubinemia Inherited hyperbilirubinemia Objective: Measurement of total and direct bilirubin is routinely performed for the differential diagnosis of hyperbilirubinemias. The diagnostic efficiency of a test is dependent on the chosen clinical decision limit. This study is designed to address the clinical decision limits for direct bilirubin. Design and methods: Routine laboratory method was used to measure total and direct bilirubin in children up to the age of 18 years. Case study data and serum from a group of healthy children were analyzed and statis- tical exercise was performed to establish decision limits. Results: The reference interval for total bilirubin was 1–12 μmol/L and for direct bilirubin 1–9 μmol/L with the median direct bilirubin of 3 μmol/L. In 17% of children with non-pathological jaundice, median total bilirubin was 173 μmol/L, median direct bilirubin was 8 μmol/L and median direct bilirubin percent was 49%. From birth direct bilirubin percentage decreased until total bilirubin was 41 μmol/L, then it remained at ≤10%. Albumin in- creased with age, and was on average 2.4 g/L higher when measured using bromocresol-green compared with bromocresol-purple. An increased amount of direct bilirubin was observed when albumin (detected using the bromocresol-purple method) was N 35 g/L. Conclusions: Direct bilirubin concentration of ≥10 μmol/L should be used to consider the presence of conju- gated hyperbilirubinemia provided that total bilirubin is also above the reference interval. A high direct bilirubin percentage is unlikely to offer any clinical value when total bilirubin is not increased. It is, however, a useful diagnostic tool when there is a persistence of hyperbilirubinemia or when total bilirubin increases during times of stress with direct bilirubin N 10%. Crown copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. Introduction A high level of measured serum total bilirubin (TBIL) establishes the presence of hyperbilirubinemia, and may help differentiate intrahepatic biliary obstruction from extrahepatic obstruction and in assessment and the prognosis of end stage liver disease. A disordered bilirubin metabolism can also result from increased production, impaired conjugation, reduced transport, and impaired excretion. Measurement of direct bilirubin (DBIL) is therefore a necessary and a useful diagnostic tool to elucidate the metabolic defect. The reference interval for TBIL is well-established [1–3] and is comprehensible to clinical professionals. Comparatively, the knowledge and interpretation of DBIL results by care-providers are not so inclusive [4,5]. The paucity of knowledge or the lack of appreciation of the clinical significance of DBIL measurement may ultimately be governed by how the result was conveyed to the care provider; that is, whether the DBIL result and its reference interval were expressed as a concentration and/or as a percentage of TBIL concentra- tion. The CALIPER (Canadian Laboratory Initiative in Pediatric Reference Intervals) Project, a collaborative study among pediatric centers across Canada, has already addressed some critical gaps in pediatric reference intervals based on factors such as age, sex, and ethnicity [3]. In this study, we report on the nature of DBIL decision limits, and, how this should be better communicated for its effective clinical utility. Methods Blood samples were collected from 946 healthy children from birth to 18 years of age, centrifuged, separated, and serum aliquots kept Clinical Biochemistry 48 (2015) 93–96 ⁎ Corresponding author. E-mail addresses: manjit.devgun@lanarkshire.scot.nhs.uk, msdevgun@googlemail.com (M.S. Devgun). 1 Senior author of the CALIPER study and the manuscript. http://dx.doi.org/10.1016/j.clinbiochem.2014.10.011 0009-9120/Crown copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved. Contents lists available at ScienceDirect Clinical Biochemistry journal homepage: www.elsevier.com/locate/clinbiochem