Development and implementation of a coagulation factor testing method utilizing autoverification in a high-volume clinical reference laboratory environment

Background: Testing coagulation factor activities requires that multiple dilutions be assayed and analyzed to produce a single result. The slope of the line created by plotting measured factor concentration against sample dilution is evaluated to discern the presence of inhibitors giving rise to nonparallelism. Moreover, samples producing results on initial dilution falling outside the analytic measurement range of the assay must be tested at additional dilutions to produce reportable results. Methods: The complexity of this process has motivated a large clinical reference laboratory to develop advanced computer algorithms with automated reflex testing rules to complete coagulation factor analysis. A method was developed for autoverification of coagulation factor activity using expert rules developed with on an off the shelf commercially available data manager system integrated into an automated coagulation platform. Results: Here, we present an approach allowing for the autoverification and reporting of factor activity results with greatly diminished technologist effort. Conclusions: To the best of our knowledge, this is the first report of its kind providing a detailed procedure for implementation of autoverification expert rules as applied to coagulation factor activity testing. Advantages of this system include ease of training for new operators, minimization of technologist time spent, reduction of staff fatigue, minimization of unnecessary reflex tests, optimization of turnaround time, and assurance of the consistency of the testing and reporting process

Sensitization profiles to hazelnut allergens across the United States

Background: Measurement of IgE antibody to hazelnut components can aid in the prediction of allergic responses to the food. Objective: To investigate the association between patient demographics (age, location) and patterns of allergic sensitization to hazelnut components across the United States and to investigate the degree of correlation between hazelnut sensitization with sensitization to other tree nuts, peanuts, and their components. Methods: Serum samples from 10,503 individuals with hazelnut extract specific IgE (sIgE) levels of 0.35 kU(A)/L or higher were analyzed for IgE antibodies to Cor a 1, 8, 9, and 14 by ImmunoCAP. A subset of these patients were analyzed for IgE antibodies to peanut, walnut, and cashew nut IgE along with associated components. Results: Among hazelnut sensitized individuals, children (<3 years old) were predominantly sensitized to Cor a 9 and Cor a 14. Conversely, Cor a 1 sIgE sensitization was much higher in adults than children, especially in the Northeastern United States. Cor a 8 sensitization was relatively constant (near 10%) across all ages. Cosensitization of hazelnut with other tree nuts and peanuts was related to correlation of IgE concentrations of individual component families. Conclusion: We conclude that sensitization to individual hazelnut components is highly dependent on age and/or geographic location. Component correlations suggest that cosensitization to hazelnut and walnut may be caused by their pathogenesis-related protein 10 allergens, nonspecific lipid transfer proteins, or seed storage proteins, whereas hazelnut and peanut cosensitization is more often caused by cross-reactivity of pathogenesis-related protein 10 (Cor a 1 and Ara h 8) and nonspecific lipid transfer proteins (Cor a 8 and Ara h 9). (c) 2018 American College of Allergy, Asthma & Immunology

Sensitization profiles to peanut allergens across the United States

Background: Measurement of IgE antibody to peanut components can aid in the prediction of allergic responses the food. Objective: To investigate the association between patient demographics (age, location) and allergic sensitization to peanut components across the United States. Methods: Serum samples from 12,155 individuals with peanut extract specific IgE levels of 0.35 kUA/L or higher were analyzed for IgE antibodies to Ara h 1, 2, 3, 8, and 9 by ImmunoCAP. Results: Among this population of peanut sensitized individuals, 79.1% of children (<3 years old) were sensitized to one or more peanut storage proteins (Ara h 1, 2, and/or 3), in contrast to 64.2% of adolescents (12-15 years old) and 22.1% of adults (>20 years old). Although sensitization was more prevalent to Ara h 2 than to the other storage proteins, a sizable fraction of patients were sensitized to Ara h 1 and/or 3 but not to Ara h 2 (eg, 13% of children <3 years old). Moreover, 9.6% of children, 10.2% of adolescents, and 10.5% of adults were sensitized to Ara h 9, whereas 2.4% of children, 49.4% of adolescents, and 42.9% of adults produced IgE to Ara h 8 (pathogenesis-related protein 10). Sensitization to Ara h 8 alone was markedly higher in the Northeastern United States relative to other regions of the country. Conclusion: We conclude that sensitization to individual peanut components is highly dependent on age and geographic location. Given that a severe allergic reaction to peanut is unlikely in individuals with isolated sensitization to Ara h 8, a sizable fraction of patients, in particular adolescents and adults, may be at lower risk than anticipated based only on demonstration of sensitization to whole peanut extract

Differences in the Distribution of IGF-I Concentrations Between European and US Populations.

peer reviewed[en] Context: Method-specific reference intervals (RIs) determine utility of IGF-I as a biomarker in GH-related diseases. Differences between populations might affect applicability of RIs. Objective: To compare population-specific RIs derived from IGF-I routine testing in laboratories in the United States and Europe using the same assay. Design and setting: Uncensored routine IGF-I testing results generated over 5 years in 4 accredited laboratories (US, n = 778 173 males/710 752 females; Europe, n = 23 220 males/40 183 females). Main outcome measures: Construction of RIs by indirect statistical methods designed to use routine testing data (modified Hoffmann approach). Comparison to published RIs, between the US and Europe, and between regions in the United States with lower and higher mean body mass indexes (BMIs). Results: Lower limits (LLs) of RIs calculated from all routine data sets do not differ from the published LLs. The same is true for upper limits (ULs) calculated from European routine data. ULs derived from US routine data are significantly higher (children, 10-18 years [mean, %]: boys + 149.3 ng/mL [+34.6%]; girls + 94.9 ng/mL [+19.8%]); adults (19-95 years: males + 45 ng/mL [+20.3%]; and females + 29.7 ng/mL [+13.8%]). Average IGF-I is higher in samples from Colorado (lower mean BMI) compared with Alabama (P < 0.0001), although the difference is smaller than between each of them and Europe. Conclusions: We provide evidence that in large datasets from the same population, direct sampling and the indirect Hoffmann approach provide comparable RIs. Although LLs are comparable between Europe and the United States, the UL is significantly higher in the United States. We suggest use of adapted RIs for the United States

Trueness, precision and stability of the LIAISON 1-84 parathyroid hormone (PTH) third-generation assay: comparison to existing intact PTH assays

BACKGROUND: Over the past few decades, parathyroid hormone (PTH) immunoassays have progressed through successive generations resulting in increased specificity and accuracy for detecting circulating PTH. With the introduction of third-generation assays, in which the biologically active PTH(1-84) is specifically targeted, the PTH(7-84) and other fragments are not detected. The specific recognition of only PTH(1-84) whole molecule allows for more reliable standardization and calibration than with the existing assays. METHODS: Samples from patients on hemodialysis or with primary hyperparathyroidism and apparently healthy subjects were examined in different collection matrices (EDTA plasma, unspun EDTA plasma and SST) stored for 0, 24 or 72 h at room temperature to reflect the prevailing sample collection methods, shipping and processing conditions of centralized labs in the United States. Samples were analyzed by the LIAISON 1-84 PTH and N-TACT assays, and by three additional commercially available intact PTH assays. RESULTS: Defined samples, prepared using two different standards (WHO 95/646 international standard and the synthetic Bachem PTH(1-84)), show little bias with the LIAISON 1-84 PTH assay, but not with the other intact PTH assays. Furthermore, PTH is stable for up to 72 h in plasma, but less stable in serum beyond 24 h. CONCLUSIONS: The FDA-approved LIAISON 1-84 PTH assay is accurate and reliably measures the biologically active PTH molecule in plasma or serum stored at room temperature for up 72 and 24 h, respectively

Vitamin D and musculoskeletal health, cardiovascular disease, autoimmunity and cancer: Recommendations for clinical practice

Recommendations were restricted to clinical practice and concern adult patients with or at risk for fractures, falls, cardiovascular or autoimmune diseases, and cancer. The panel reached substantial agreement about the need for vitamin D supplementation in specific groups of patients in these clinical areas and the need for assessing their 25-hydroxyvitamin D (25(OH)D) serum levels for optimal clinical care. A target range of at least 30 to 40 ng/mL was recommended. As response to treatment varies by environmental factors and starting levels of 25(OH)D, testing may be warranted after at least 3 months of supplementation. An assay measuring both 25(OH)D(2) and 25(OH)D(3) is recommended. Dark-skinned or veiled individuals not exposed much to the sun, elderly and institutionalized individuals may be supplemented (800 IU/day) without baseline testing