Indirectly determined reference intervals for automated white blood cell differentials of pediatric patients in Berlin and Brandenburg.

OBJECTIVES: Establishing direct reference intervals for pediatric patients is a costly, challenging, and time-consuming enterprise. Indirectly established reference intervals can help to ameliorate this situation. It was our objective to establish population-specific reference intervals for automated white blood cell differentials via data mining and non-parametric percentile method. METHODS: Blood counts and automated white blood cell differentials of patients aged 0 days to 18 years, performed from the 1st of January 2018 until the 30th of June 2022, were identified in our laboratory information system. Reference intervals were established in accordance with IFCC and CLSI recommendations as well as the propositions by Haeckel et al. RESULTS: Initially, 47,173 blood counts on our SYSMEX XN-9000 were identified. 11,707 data sets were excluded, leaving 35,466 sample sets for analysis. Of these, 17,616 contained automated white blood cell differentials. Due to insufficient patient numbers, no reference intervals for automated white blood cell differentials could be established for children aged <7 months. In comparison to the corresponding reference intervals published by Herklotz et al., reference intervals determined by us showed relevant differences throughout all age groups. CONCLUSIONS: The combination of non-parametric percentile method and the propositions by Haeckel et al. utilizing conscientious data mining appears to be potent alternative to direct reference interval determination.

Indirectly determined hematology reference intervals for pediatric patients in Berlin and Brandenburg.

OBJECTIVES: Establishing direct reference intervals (RIs) for pediatric patients is a very challenging endeavor. Indirectly determined RIs can address this problem by utilization of existing clinical laboratory databases. In order to provide better laboratory services to the local pediatric population, we established population-specific hematology RIs via data mining. METHODS: Our laboratory information system (LIS) was searched for pediatric blood counts of patients aged from 0 days to 18 years, performed from 1st of January 2018 until 31st of March 2021. In total, 27,554 blood counts on our SYSMEX XN-9000 were initially identified. After application of pre-defined exclusion criteria, 18,531 sample sets remained. Age- and sex-specific RIs were established in accordance with International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and Clinical & Laboratory Standards Institute (CLSI) recommendations. RESULTS: When compared to pediatric RIs supplied by other authors, the RIs determined specifically for pediatric patients from Berlin and Brandenburg showed several relevant differences, especially with regard to white blood cell counts (WBCs), red blood cell counts (RBCs), red cell distribution widths (RDW) and platelet counts (PLTs) within the distinct age groups. Additionally, alterations to several published age-specific partitions had to be made, while new sex-specific partitions were introduced for WBCs and PLTs. CONCLUSIONS: Generic RIs from textbooks, manufacturer information and medical publications - even from nationwide or multicenter studies - commonly used in many laboratories might not reflect the specifics of local patient populations properly. RIs should be tailored to the serviced patient population whenever possible. Careful data mining appears to be suitable for this task.

Interference From High-Dose Biotin Intake in Immunoassays for Potentially Time-Critical Analytes by Roche.

CONTEXT.­: Immunoassays using the interaction between streptavidin and biotin are used for clinical chemical analytes on platforms by many different manufacturers. The design can be susceptible to interference from high-dose biotin intake in patients, which remains an often-overlooked confounder despite recently increased awareness. OBJECTIVE.­: To evaluate an easily implementable method of in vitro biotin depletion for the removal of biotin interference in immunoassays for potentially time-critical analytes. DESIGN.­: A biotin stock solution was made and de-identified patient samples were spiked to reach a biotin concentration of 1.126 × 106 pg/mL, the maximum reported biotin concentration 1 to 2 hours after a single oral dose of 300 mg biotin. Then, the resulting interference in Elecsys immunoassays for cortisol, cyclosporine A, tacrolimus, digitoxin, thyroid-stimulating hormone, free triiodothyronine, free thyroxine, C-peptide, insulin, N-terminal pro-B-type natriuretic peptide, troponin T high sensitive, human immunodeficiency virus, procalcitonin, ß human chorionic gonadotropin, toxoplasma immunoglobulin M, and toxoplasma immunoglobulin G was evaluated before and after biotin depletion using streptavidin particles. RESULTS.­: All tested immunoassays, with the exception of toxoplasma immunoglobulin M and toxoplasma immunoglobulin G, suffered from significant biotin interference. The depletion protocol removed assay interference due to biotin and produced results that were close or identical to initial prespike measurements. CONCLUSIONS.­: Despite an increase in turnaround times, biotin adsorption is a feasible countermeasure for biotin interference in Elecsys immunoassays. Until test kits with an increased resistance to the interference from high-dose biotin intake are distributed, the evaluated protocol can provide results properly reflecting the patient's clinical condition.

Persistent Isolated Elevation of Aspartate Aminotransferase in an Asymptomatic Female Patient: a Case Report and Review of Current Literature.

BACKGROUND: Persistent isolated elevation of aspartate aminotransferase (AST) is a rare observation and might lead to unnecessary laboratory testing and invasive procedures, if the possibility of macro-AST is not considered. METHODS: We report the case of a healthy 28-year-old female patient with persistent isolated elevation of AST. In order to confirm the suspected diagnosis of macro-AST, polyethylene glycol (PEG) precipitation and repeated measurements of enzyme activity after refrigeration at 2 - 8°C were performed. RESULTS: PEG precipitation confirmed the presence of macro-AST, while repeated measurements after refrigeration did not show any relevant decrease in enzyme activity. CONCLUSIONS: Especially in clinically asymptomatic patients, macro-AST must be considered as a cause of persistent isolated elevations in AST activity to avoid costly and potentially harmful medical tests or procedures. PEG precipitation is a feasible and cost-effective way to establish the diagnosis, while repeated measurement of enzyme activity after refrigeration potentially leads to wrong conclusions.

Interference of High Dose Biotin Supplementation with Thyroid Parameters in Immunoassays Utilizing the Interaction between Streptavidin and Biotin: a Case Report and Review of Current Literature.

BACKGROUND: Automated immunoassays utilizing the interaction between streptavidin and biotin are widely used. Nonetheless, biotin remains an often overlooked confounder. METHODS: We report the case of a 54-year-old female patient with progressive multiple sclerosis and Hashimoto's thyroiditis who presented herself for a follow-up. Measurements on Roche's cobas® 8000 modular analyzer series suggested severe hyperthyroidism. Initially, no relevant confounders could be identified. RESULTS: All requested thyroid parameters were measured with alternative methods, yielding plausible results. CONCLUSIONS: Biotin is a significant confounder in many immunoassays. Alternative measurement methods or methods of biotin neutralization need to be implemented for certain situations.