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Background Hemolysis is a common reason for nonreporting results in biochemistry and is measured using the hemolysis index (HI), with nonreporting limits set for analytes by manufacturers. Objective To verify the nonreporting HI limit for potassium, phosphate, magnesium, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), iron, CA19-9, and vitamin D on the Beckman Coulter AU5800/DxI800 analyzers. Method Hemolysate was created from EDTA-lined tubes of whole blood using an osmotic shock procedure. The hemolysate underwent serial dilutions with saline and was spiked in paired serum. The delta changes in HI and analyte concentration were measured, assessed using regression analysis, and compared against calculated reference change values. Results A linear relationship between increasing HI and increasing analyte concentration (R 2 > 0.9) was observed for potassium (y = 0.8864x), phosphate (y = 0.1079x), magnesium (y = 0.0678x), AST (y = 29.035x), and LDH (y = 350x). Increasing HI values did not have a linear effect on iron (y = −0.2544x), CA19-9 (y = 2.7019x), or vitamin D (y = 8.036x) concentrations. Conclusion The results from this experiment support increasing the HI nonreporting limit to 100 mg/dL for potassium; 200 mg/dL for magnesium; and 300 mg/dL for phosphate, CA19-9, and vitamin D. The iron assay is not affected by hemolysis as high as 500 mg/dL. The current HI nonreporting limit of 50 mg/dL is appropriate for LDH. [ABSTRACT FROM AUTHOR]

An 81-year-old man was admitted to hospital with symptomatic coronavirus disease (COVID-19) infection. He had a background of progressive chronic inflammatory demyelinating polyneuropathy associated with Waldenstrom's macroglobulinaemia. His plasma creatinine on four separate samples was inconceivably low (all ≤13 μmol/L), as measured by a Beckman Coulter enzymatic assay) after being 72 μmol/L 3 months earlier. On further investigation, his serum immunoglobulin M (IgM) was 15.4 g/L and his plasma creatinine measured by Roche enzymatic and Roche Jaffe methods was 62 μmol/L and 64 μmol/L, respectively. This was consistent with results post dilution studies and polyethylene glycol (PEG) precipitation on the Beckman Coulter assay. There was no evidence of similar interference when reviewing creatinine results from 10 other patients with IgM paraproteinaemia who had been tested in our laboratory. Clinicians and laboratorians are reminded that enzymatic creatinine is not free from interferences. IgM paraprotein negative interference of enzymatic creatinine is rare and specific to a patient's IgM and assay combination, but should be considered in patients with an unexplained low enzymatic creatinine result. Useful investigations to identify an interference include dilution studies, PEG precipitation and measuring creatinine on an alternative method such as Jaffe, mass spectrometry or an enzymatic method from a different platform. [ABSTRACT FROM AUTHOR]

Abstract Background The ovarian reserve in women is known to correlate with anti-Müllerian hormone (AMH) levels, and currently the latest, third-generation, fully-automated AMH immunoassays, such as Access and Cobas, are beginning to be used for measuring AMH levels. However, the age-specific reference values obtained for AMH levels have been based on samples from an American population, measured using first-generation immunoassays. In this study, we attempted to determine the age-specific AMH reference values based on a large set of samples taken from Japanese infertile women measured by Access so that they could be used by infertility centers treating Japanese and those with similar racial and life-style characteristics. Methods The study included 5483 Japanese patients who enrolled in infertility treatment programs at two in-vitro fertilization centers, Shimbashi YUME Clinic and Natural ART Clinic Nihombashi in Tokyo, and who had their serum AMH levels measured between December 2015 and November 2017 by Access. Each patient was represented only once in the study. The mean, median, and standard deviation values were obtained from the measured values for single-year intervals from 28 through 48 years of age (21 age groups in total). The 3D-fitted curve of age-specific mean and median values measured by Access was obtained by regression analysis. Results The mean and median values decreased with advancing age (mean: R2 = 0.9864; median: R2 = 0.9926). In all age groups, the mean values were higher than the median values; however, the differences between these values decreased with increasing age. Conclusions The age-specific AMH reference values measured by Access in this study may serve as a useful diagnostic marker in infertility centers, especially those treating Japanese patients or patients with similar characteristics.

Objectives: Accurate hematologic test interpretation based on normative reference standards is critical to ensure appropriate clinical decision making. However, healthy pediatric reference data for most hematology parameters are lacking. To address this gap, this study establishes age- and sex-specific hematologic reference standards in the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) cohort of healthy children and adolescents.Methods: Fresh whole blood samples collected from a total of 566 healthy children and adolescents (birth to <21 years) with informed consent were analyzed for 47 hematologic parameters on the Beckman Coulter DxH 900. Age- and sex-specific reference standards were calculated based on the Clinical and Laboratory Standards Institute guidelines.Results: Reference value distributions for most hematology parameters demonstrated dynamic changes across the pediatric age range with significant age-specific differences observed for 39 of the 47 parameters examined. Sex-specific differences were also observed for eight hematologic parameters, primarily during and after puberty.Conclusions: This study establishes a robust database of pediatric reference standards for 47 hematologic parameters in the CALIPER cohort for the first time. These comprehensive reference value data sets report potentially important and physiologically relevant trends in hematologic markers, clearly demonstrating the need for pediatric reference standards for hematologic test interpretation. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to establish comprehensive age- and sex-specific reference intervals for hematologic parameters in the CALIPER cohort of healthy children and adolescents.Methods: A total of 536 healthy children and adolescents (birth to 21 years) were recruited with informed consent, and whole blood samples were analyzed for 27 hematologic parameters on the Beckman Coulter DxH 520 system. Age- and sex-specific pediatric reference standards were established. Reference values obtained on the DxH 520 were also compared with data obtained on a larger laboratory-based instrument (DxH 900).Results: Most hematologic parameters showed significant age- and/or sex-specific changes during growth and development. Of the 27 hematologic parameters, all except four (mean corpuscular hemoglobin concentration, basophil percentage, low hemoglobin density, immature cell percentage) required age partitioning, and eight required sex partitioning.Conclusions: This study establishes a robust pediatric hematology reference database that will assist in more accurate test result interpretation. Our data clearly demonstrate significant variation in hematologic parameter concentrations in children and adolescents, necessitating the use of pediatric-specific reference standards. [ABSTRACT FROM AUTHOR]

• We compared the Beckman hsTnI assay between DxI800 to Access2 platforms across multiple sites. • DxI800 and Access2 were robust across sites, but some differences were noted at low concentrations. • DxI800 analytical sensitivity was lower than Access2. • DxI800 runs significantly higher than Access2 at low concentrations <10 ng/L. • Platform-specific differences are important factors to consider when establishing common clinical cutoffs. Previous analytical evaluations of the Beckman Coulter Access high sensitivity troponin (hsTn) I assay have focused on single platforms and laboratory sites. The purpose of this study was to determine assay robustness across different platforms at multiple sites, platform-specific characteristics, and equivalence to other hsTn methods in a large laboratory network. Barricor plasma was used to assess imprecision, linearity, sensitivity (limit of blank and detection, LOB/LOD), and comparability to the conventional AccuTnI+3 and other hsTn assays. Various studies were conducted across a total of 9 laboratories using Beckman DxI800 and Access2 platforms. Within-laboratory precision was <10% across all target patient pool concentrations, however, DxI800 mean values were 20% higher than Access2 in the range of 3.6–44.9 ng/L. LOBs and LODs were lower on DxI800, 0.27 and 0.90 ng/L, respectively, compared to 2.9 and 3.2 ng/L, on Access2. Both showed excellent linearity across the full range. In method comparison to AccuTnI+3, DxI800 had a higher slope (0.9417 versus 0.8495) and positive bias (+18.1% versus −9.9%) compared to Access2, a trend further pronounced at concentrations <150 ng/L. At values <150 ng/L, there was good agreement with Abbott hsTnI (slope = 1.017, r = 0.932), but poor agreement with the Roche hsTnT assay (slope = 1.687, r = 0.589). Inter-laboratory split sample comparisons across 2 DxI800 and 7 Access2 sites showed close agreement, except at low concentrations <10 ng/L where DxI800 was 2.8 ng/L higher (p<0.001). The Beckman hsTnI assay showed robust analytical performance across different laboratories and platforms. However, discrepancies between platforms were found at low concentrations where rapid acute myocardial infarction (AMI) rule-out decisions occur. These differences have important implications for AMI risk assessment, suggesting that laboratories should develop platform-specific parameters rather than using them interchangibly. [ABSTRACT FROM AUTHOR]

Introduction Beckman Coulter recently reformulated their commercial TSH assay with primary calibration to the World Health Organization 3rd TSH international standard. An extensive evaluation of the performance characteristics for this assay was completed. Methods Intra-day and inter-day precision was evaluated using 3 concentrations of commercial quality control material. Linearity, reportable range, stability, sensitivity and susceptibility to common inferences were determined using pooled patient specimens. Inter-assay variability was assessed across 5 different platforms (n = 47 patient specimens). Results Intra-day and inter-day CVs were < 10% at all concentrations evaluated. The LOQ, LOD and LOB were 0.0047 μ IU/ml (10% CV), 0.0012 μ IU/ml and 0.0005 μ IU/ml, respectively. Variable bias was observed for the TSH3 assay when evaluated against the previous generation assay and other platforms, but overall TSH3 gave comparable results. Conclusions The TSH3 assay for UniCel DxI 800, is precise, highly sensitive and comparable to the previous generation assay. The assay is acceptable for clinical testing. [ABSTRACT FROM AUTHOR]

Aim of the study Recently, Beckman Coulter Diagnostics set up a new TSH immunoassay for the automated DxI platform. The aim of this study was to evaluate and compare the analytical performance and clinical results of this method with those of previous method. Material and methods A multicenter study (named TSH ELAS Study) was organized using 593 serum samples, collected from healthy subjects and patients with thyroid disorders, and 13 control samples, circulated in an External Quality Assessment (EQA) scheme. Results The values of LoB and LoD, and LoQ at 20% CV were 0.0004 mIU/L, 0.001 mIU/L and 0.0023 mIU/L, respectively. Moreover, TSH concentrations > 0.01 mIU/L actually show imprecision values lower than 5% CV. This new TSH assay showed a systematic underestimation (on average of 6.25%) compared to old method, which is mainly due to larger differences between methods for samples with low TSH concentrations, related to the better analytical sensitivity of new compared to old method. In a reference population, including 279 apparently healthy adult subjects, Caucasian volunteers (mean age 43.6 years, age 20–63 years, 138 women and 141 males) the distribution of TSH concentrations was: mean (CI 95%) 1.694 mIU/L (1.588–1.779), median 1.495 mIU/L (1.412–1.588 mIU/L), 97.5th percentile 3.707 mIU/L. Conclusions The new TSH immunoassay for DxI platform shows some relevant improvements compared to the previous one: use of the most recent WHO 3rd IRP 81/563 standard and monoclonal antibodies (instead of polyclonal antibodies of the old method), and better analytical sensitivities and reproducibility. [ABSTRACT FROM AUTHOR]

Objectives Anti-Müllerian hormone (AMH) measurement is useful as an aid in the evaluation of ovarian reserve. In the past, its conventional use was restricted by the low-throughput and variability of existing manual AMH assays. We developed the automated Access AMH assay for the quantitative determination of AMH levels on the Access family of immunoassay systems. The analytical performance of this new assay was evaluated. Design and methods Sensitivity, dilution linearity, assay imprecision, AMH sample stability, lot-to-lot comparison and correlation with AMH Gen II assay (Beckman Coulter, Inc.) were evaluated. Reference intervals for Access AMH were established in healthy females, males, newborns (≤ 60 days) and pediatric males classified by Tanner stages. Results The limit of blank and limit of detection were below 0.0077 and 0.0098 ng/mL, respectively. The limit of quantitation was 0.010 ng/mL. The total imprecision ranged from 2.4 to 5.2%. Linearity was observed up to 24 ng/mL. Sample storage at room temperature up to 48 h, at 2–8 °C up to 7 days and at − 20 °C up to 15 months had no impact on measured AMH. The correlation study gave a coefficient between 0.99 and 1 and a regression slope between 0.89 and 0.92. Excellent lot-to-lot comparability was observed on controls and patient samples with a maximum bias of 3.7% between 2.81 and 15.03 ng/mL. Conclusions The fully automated Access AMH immunoassay demonstrates excellent analytical performance. As a consequence, the availability of this assay will represent a robust, fast and precise alternative to manual AMH assay testing. [ABSTRACT FROM AUTHOR]

Background: The manual Generation II (Gen II) ELISA method used to measure Anti-Müllerian Hormone (AMH) from Beckman Coulter has recently been superseded by a fully automated AMH immunoassay. The aim of this study was to evaluate the performance of the Access AMH assay and directly compare it to the modified Gen II ELISA method. A secondary aim was to verify that the fertile age-related AMH range previously established using the Gen II ELISA could be used to interpret results from the new automated Access assay. Methods: The precision, stability, linearity, measurement range and detection limits were determined using recombinant AMH and patient serum samples. Different diluents and their effects on AMH concentration were compared. A correlation study was performed on patient samples to compare the Access AMH assay to the ELISA method on the Access2 and DxI800 analysers. The fertile AMH range was verified by comparing the 10th, 50th and 90th percentile values from both methods obtained from 489 natural conception pregnant women. Results: The Access AMH assay showed good performance across the measuring range for both intra-assay (CV 1.41-3.30 %) and inter-assay (CV 3.04-5.76 %) precision and acceptable sample stability. Dilution of the high concentration samples with the recommended diluent resulted in a small but significant downward shift in values. The assay was linear over the range of values recommended by the manufacturer, allowing for accurate reporting within the reported range. The two assay types were highly correlated (R2 = 0.9822 and 0.9832 for Access2 and DxI800, respectively), and the differences observed between the Access2 and DxI800 analysers were within clinically acceptable ranges, indicating that the methods are interchangeable. Furthermore, we demonstrated that results from the published reference range for the Gen II ELISA correlate with those from the automated Access AMH assay. Conclusion: Here, we verified the published performance of the Access AMH assay and showed excellent correlation with the Gen II ELISA method. Moreover, we validated this correlation by confirming that the results from a fertile AMH reference range established using the preceding Gen II ELISA are interchangeable with the new automated Access AMH assay. [ABSTRACT FROM AUTHOR]

Background Beckman Coulter recently introduced a new hCG assay manufactured for the Access 2 and DxI platforms. This assay is the first to use the 5th International Standard (5th IS) as its primary calibration material. Clinical laboratories are required to validate the method performance before testing and reporting patient results. Methods Beckman Coulter Access 2 instruments (n = 41) across Kaiser Permanente Northern California were evaluated for their performance characteristics using the hCG5 reagent. Precision, linearity, dilution verification, and patient sample comparisons were performed on each instrument. Results The assay was linear up to 1350 IU/L. Intra-day and inter-day precision ranged from 1.0%–3.3% and 1.8–7.3%, respectively, for the low QC material (mean concentration 4.6 IU/L). Percent bias between the previous assay (hCG2) and the hCG5 assay was 3.2 to 22.7% for hCG concentrations < 1000 IU/L and − 2.9 to 30% for concentrations > 1000 IU/L. On board and manual dilutions agreed within 15% following proper adjustment of the instrument dilution factor. Conclusions Achieving Access 2 inter-instrument agreement on specimens needing dilutions (hCG > 1350 IU/L) requires validation of the on board dilution factor. Laboratories should use QC material above the linear range to monitor instrument dilution accuracy and precision. [ABSTRACT FROM AUTHOR]

Background High doses of hydroxocobalamin (OHCob) are used to treat cyanide poisoning and cardiac complications. Since OHCob absorbs at multiple wavelengths often used in colorimetric assays, spurious laboratory results are likely to occur. The objective of this study was to examine interference caused by OHCob in colorimetric assays measured using the Beckman Coulter DxC and AU680. Methods OHCob was dissolved in water and spiked into pooled “healthy” and “unhealthy” patient samples at two different concentrations (0.15 and 1.5 mg/mL). Spiked and unspiked samples were analyzed on both instruments and bias was calculated. A total of 23 analytes were tested on the DxC and 27 analytes were tested on the AU680. For analytes showing a bias ≥ 10%, OHCob was titrated from 0.2–1.5 mg/mL. Results The following analytes were affected on the DxC and AU680: alanine aminotransferase, amylase, total bilirubin, cholesterol, creatine kinase, creatinine, magnesium, uric acid. Direct bilirubin, iron, phosphate, total protein and triglycerides were only affected on the DxC. Biases observed were positive or negative and fixed or proportional. Conclusions Between the DxC and AU680, several analytes were affected at therapeutic OHCob concentrations. Hence, it is important for laboratories to know how their instruments are affected, and for clinicians to alert the lab when these samples are expected. [ABSTRACT FROM AUTHOR]

A high-throughput screening protocol has been developed for Mycobacterium tuberculosis glutamine synthetase by quantitative estimation of inorganic phosphate. The Km values determined at pH 6.8 are 22 mM for L-glutamic acid, 0.75 mM for NH4Cl, 3.25 mM for MgCl2, and 2.5 mM for adenosine triphosphate. The Km value for glutamine is affected significantly by the increase in pH of assay buffer. At the saturating level of the substrate, the enzyme activity at pH 6.8 and 25° C is found to be linear up to 3 h. The reduction of enzyme activity is negligible even in presence of 10% DMSO. The Z′ factor and signal-to-noise ratio are found to be 0.75 and 6.18, respectively, when the enzyme is used at 62.5 μg/ml concentration. The IC50 values obtained at pH 6.8 for both L-methionine S-sulfoximine and DL-phosphothriacin are 500 μM and 30 μM, respectively, which is lowest compared to the values obtained at other pH levels. The Beckman Coulter high-throughput screening platform was found to take 5 h 9 min to complete the screening of 60 plates. For each assay plate, a replica plate is used to normalize the data. Screening of 1164 natural product fractions/extracts and synthetic molecules from an in-house library was able to identify 12 samples as confirmed hits. Altogether, the validation data from screening of a small set of an in-house library coupled with Z′ and signal-to-noise values indicate that the protocol is robust for high-throughput screening of a diverse chemical library. [ABSTRACT FROM PUBLISHER]

Background: The ovarian reserve in women is known to correlate with anti-Müllerian hormone (AMH) levels, and currently the latest, third-generation, fully-automated AMH immunoassays, such as Access and Cobas, are beginning to be used for measuring AMH levels. However, the age-specific reference values obtained for AMH levels have been based on samples from an American population, measured using first-generation immunoassays. In this study, we attempted to determine the age-specific AMH reference values based on a large set of samples taken from Japanese infertile women measured by Access so that they could be used by infertility centers treating Japanese and those with similar racial and life-style characteristics.Methods: The study included 5483 Japanese patients who enrolled in infertility treatment programs at two in-vitro fertilization centers, Shimbashi YUME Clinic and Natural ART Clinic Nihombashi in Tokyo, and who had their serum AMH levels measured between December 2015 and November 2017 by Access. Each patient was represented only once in the study. The mean, median, and standard deviation values were obtained from the measured values for single-year intervals from 28 through 48 years of age (21 age groups in total). The 3D-fitted curve of age-specific mean and median values measured by Access was obtained by regression analysis.Results: The mean and median values decreased with advancing age (mean: R2 = 0.9864; median: R2 = 0.9926). In all age groups, the mean values were higher than the median values; however, the differences between these values decreased with increasing age.Conclusions: The age-specific AMH reference values measured by Access in this study may serve as a useful diagnostic marker in infertility centers, especially those treating Japanese patients or patients with similar characteristics. [ABSTRACT FROM AUTHOR]