scholarly journals Diurnal variation of leukocyte counts affects the indirect estimation of reference intervals

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Antje Torge ◽  
Rainer Haeckel ◽  
Mustafa Özcürümez ◽  
Alexander Krebs ◽  
Ralf Junker
Keyword(s):  
Diurnal Variation ◽  
Indirect Method ◽  
Venous Blood ◽  
Direct Methods ◽  
Reference Intervals ◽  
Indirect Methods ◽  
Indirect Estimation ◽  
Late Afternoon ◽  
Reference Limits ◽  
Leukocyte Counts

Abstract It has been observed that the estimation of reference intervals of leukocytes in whole venous blood leads to higher upper reference limits (uRLs) with indirect methods than has been reported in the literature determined by direct approaches. This phenomenon was reinvestigated with a newer, more advanced indirect method, and could be confirmed. Furthermore, a diurnal variation was observed with lower values during the morning and higher values in the late afternoon and at night. This observation can explain why indirect approaches using samples collected during 24 h lead to higher uRLs than direct methods applied on samples collected presumably in the morning.

A new indirect estimation of reference intervals: truncated minimum chi-square (TMC) approach

2019 ◽  
Vol 57 (12) ◽  
pp. 1933-1947 ◽  
Author(s):  
Werner Wosniok ◽  
Rainer Haeckel
Keyword(s):  
Detection Limit ◽  
Simulated Data ◽  
Reference Interval ◽  
Reference Intervals ◽  
Skewed Data ◽  
Chi Square ◽  
Indirect Methods ◽  
Indirect Estimation ◽  
Estimated Parameters ◽  
Data Files

Abstract All known direct and indirect approaches for the estimation of reference intervals (RIs) have difficulties in processing very skewed data with a high percentage of values at or below the detection limit. A new model for the indirect estimation of RIs is proposed, which can be applied even to extremely skewed data distributions with a relatively high percentage of data at or below the detection limit. Furthermore, it fits better to some simulated data files than other indirect methods. The approach starts with a quantile-quantile plot providing preliminary estimates for the parameters (λ, μ, σ) of the assumed power normal distribution. These are iteratively refined by a truncated minimum chi-square (TMC) estimation. The finally estimated parameters are used to calculate the 95% reference interval. Confidence intervals for the interval limits are calculated by the asymptotic formula for quantiles, and tolerance limits are determined via bootstrapping. If age intervals are given, the procedure is applied per age interval and a spline function describes the age dependency of the reference limits by a continuous function. The approach can be performed in the statistical package R and on the Excel platform.

scholarly journals Indirect methods for reference interval determination – review and recommendations

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Graham R.D. Jones ◽  
Rainer Haeckel ◽  
Tze Ping Loh ◽  
Ken Sikaris ◽  
Thomas Streichert ◽  
...  
Keyword(s):  
Clinical Chemistry ◽  
Direct Methods ◽  
Analytical Techniques ◽  
Reference Interval ◽  
Reference Population ◽  
Reference Intervals ◽  
Statistical Techniques ◽  
Indirect Methods ◽  
Indirect Approach ◽  
Patient Health

Abstract Reference intervals are a vital part of the information supplied by clinical laboratories to support interpretation of numerical pathology results such as are produced in clinical chemistry and hematology laboratories. The traditional method for establishing reference intervals, known as the direct approach, is based on collecting samples from members of a preselected reference population, making the measurements and then determining the intervals. An alternative approach is to perform analysis of results generated as part of routine pathology testing and using appropriate statistical techniques to determine reference intervals. This is known as the indirect approach. This paper from a working group of the International Federation of Clinical Chemistry (IFCC) Committee on Reference Intervals and Decision Limits (C-RIDL) aims to summarize current thinking on indirect approaches to reference intervals. The indirect approach has some major potential advantages compared with direct methods. The processes are faster, cheaper and do not involve patient inconvenience, discomfort or the risks associated with generating new patient health information. Indirect methods also use the same preanalytical and analytical techniques used for patient management and can provide very large numbers for assessment. Limitations to the indirect methods include possible effects of diseased subpopulations on the derived interval. The IFCC C-RIDL aims to encourage the use of indirect methods to establish and verify reference intervals, to promote publication of such intervals with clear explanation of the process used and also to support the development of improved statistical techniques for these studies.

scholarly journals Review of potentials and limitations of indirect approaches for estimating reference limits/intervals of quantitative procedures in laboratory medicine

2021 ◽  
Vol 45 (2) ◽  
pp. 35-53
Author(s):  
Rainer Haeckel ◽  
Werner Wosniok ◽  
Thomas Streichert
Keyword(s):  
Direct Methods ◽  
Reference Population ◽  
Reference Intervals ◽  
Simulation Studies ◽  
Indirect Methods ◽  
Medical Laboratories ◽  
Pathological Conditions ◽  
Crucial Difference ◽  
External Sources ◽  
Direct And Indirect Methods

Abstract Reference intervals (RIs) can be determined by direct and indirect procedures. Both approaches identify a reference population from which the RIs are defined. The crucial difference between direct and indirect methods is that direct methods select particular individuals after individual anamnesis and medical examination have confirmed the absence of pathological conditions. These individuals form a reference subpopulation. Indirect methods select a reference subpopulation in which the individuals are not identified. They isolate a reference population from a mixed population of patients with pathological and non-pathological conditions by statistical reasoning. At present, the direct procedure internationally recommended is the “gold standard”. It has, however, the disadvantage of high expenses which cannot easily be afforded by most medical laboratories. Therefore, laboratories adopt RIs established by direct methods from external sources requiring a high responsibility for transference problems which are usually neglected by most laboratories. These difficulties can be overcome by indirect procedures which can easily be performed by most laboratories without causing economic problems. The present review focuses on indirect approaches. Various procedures are presented with their benefits and limitations. Preliminary simulation studies indicate that more recently developed concepts are superior to older approaches.

Definition of Reference Limits for Autoantibodies to Thyroid Peroxidase and Thyroglobulin in a Large Population of Outpatients Using an Indirect Method Based on Current Data

2008 ◽  
Vol 132 (12) ◽  
pp. 1924-1928 ◽  
Author(s):  
Renato Tozzoli ◽  
Davide Giavarina ◽  
Danilo Villalta ◽  
Giuliano Soffiati ◽  
Nicola Bizzaro
Keyword(s):  
Information System ◽  
Indirect Method ◽  
Direct Method ◽  
Large Population ◽  
Direct Methods ◽  
Current Data ◽  
Thyroid Peroxidase ◽  
Thyroid Antibodies ◽  
Upper Limits ◽  
Reference Limits

Abstract Context.—The reference limits for thyroid antibodies are generally made by measuring thyroid peroxidase and thyroglobulin antibody values in a group of healthy subjects (direct method), as proposed by the National Academy of Clinical Biochemistry. Objective.—To define the upper reference limits of thyroid peroxidase and thyroglobulin, by using an indirect method to analyze data from a large number of outpatients that were stored in the information system of a general hospital laboratory. Design.—Thyroid peroxidase and thyroglobulin values from 21 492 patients, who had undergone antithyroid antibody measurements, were retrieved from the laboratory information system; the upper reference limits (in the top 97.5 percentile) were calculated using the indirect Kairisto method, after exclusion of outliers. Results.—The mean upper reference limits for females and males were 15 kIU/L and 9 kIU/L for thyroid peroxidase, and 21 kIU/L and 19 kIU/L for thyroglobulin, respectively. The upper limits showed minimal or no differences in the different age classes in either females or males. Conclusions.—Using a vast population of patients, we demonstrated that the upper limits for thyroid antibodies are much lower than the values obtained with classic, direct methods and that they do not vary in relation to age and sex.

scholarly journals Calculation of indirect reference intervals of plasma lipase activity of adults from existing laboratory data based on the Reference Limit Estimator integrated in the OPUS::L information system

2021 ◽  
Vol 45 (2) ◽  
pp. 131-134
Author(s):  
Britta Amodeo ◽  
Aline Schindler ◽  
Ulrike Schacht ◽  
Hans Günther Wahl
Keyword(s):  
Information System ◽  
Lipase Activity ◽  
Clinical Chemistry ◽  
Laboratory Data ◽  
Direct Methods ◽  
Reference Interval ◽  
Reference Intervals ◽  
Specific Reference ◽  
Reference Limit ◽  
Reference Limits

Abstract Objectives Most laboratories have difficulties to determine their own reference intervals for the diagnostic evaluation of patient results by direct methods. Therefore, data is often just taken from the literature or package inserts of the analytical tests. Methods The section on Reference Limits of the German Society for Clinical Chemistry and Laboratory Medicine (DGKL) first uploaded the Reference Limit Estimator (RLE) as an R-program with MS Excel-interface on the DGKL home page and now this tool is implemented in the commercial Laboratory Information System OPUS::L (OSM AG Essen, Germany). We used this OPUS::L “Population specific Reference Limits” tool online with our laboratory database. First calculations were done using the example of lipase. Results The manufacturer’s original reference interval for lipase 12–53 U/L (adults) was changed to age dependent upper reference limits of <41 U/L (<20 years), <60 U/L (20–80 years) and <70 U/L (>80 years). Conclusions By means of the OPUS::L “Population specific Reference Limits” tool we were able to establish our laborarotry specific reference interval for plasma lipase activity. The new reference limits helped to solve an old problem of implausible low elevated lipase values.

scholarly journals Observational Study on Variation of Longitudinal Platelet Counts in Calves over the First 14 Days of Life and Reference Intervals from Cross-Sectional Platelet and Leukocyte Counts in Dairy Calves up to Two Months of Age

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 347
Author(s):  
Emma Strous ◽  
Arne Vanhoudt ◽  
Anja Smolenaars ◽  
Gerdien van Schaik ◽  
Matthijs Schouten ◽  
...  
Keyword(s):  
Platelet Count ◽  
Observational Study ◽  
Reference Intervals ◽  
Dairy Calves ◽  
Cross Sectional ◽  
Adult Cattle ◽  
Platelet Counts ◽  
Holstein Friesian ◽  
Leukocyte Counts ◽  
Count Reference

Platelet and leukocyte count reference intervals (RIs) for cattle differ by age and while adult RIs are known, RIs for calves are studied less. The aims of this observational study are to evaluate variation of platelet counts of Holstein Friesian calves over the first 14 days of life and to propose RIs for platelet and leukocyte counts of Holstein Friesian calves aged 0–60 days. In a longitudinal study, 19 calves were blood sampled 17 times, in the first 14 days of their lives. Blood was collected in a citrate blood tube and platelet counts were determined. We assessed the course of platelet counts. In a field study, 457 healthy calves were blood sampled once. Blood was collected in an EDTA blood tube and platelet and leukocyte counts were determined. The RIs were calculated by the 2.5 and 97.5 percentiles. Platelet counts started to increase 24 h after birth (mean platelet count 381 × 109/L ± 138 × 109/L) and stabilized after five days (mean platelet count 642 × 109/L ± 265 × 109/L). In calves up to six days of age, platelet counts were lower than in calves older than five days. In conclusion, the RIs of platelet and leukocyte counts in calves were wider in range than the RIs for adult cattle, therefore, calf specific RIs for platelet and leukocyte counts should be used. From 6 until 60 days of age, we propose an RI for platelet counts of 287–1372 × 109/L and for the first 60 days of life an RI for leukocyte counts of 4.0–18.9 × 109/L.

Reference intervals for venous blood gas measurement in adults

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Kirsty L. Ress ◽  
Gus Koerbin ◽  
Ling Li ◽  
Douglas Chesher ◽  
Phillip Bwititi ◽  
...  
Keyword(s):  
Partial Pressure ◽  
Meta Analysis ◽  
Venous Blood ◽  
Reference Interval ◽  
Reference Intervals ◽  
Published Data ◽  
Blood Gas ◽  
Arterial Blood Gas ◽  
Arterial Blood ◽  
Venous Blood Gas

AbstractObjectivesVenous blood gas (VBG) analysis is becoming a popular alternative to arterial blood gas (ABG) analysis due to reduced risk of complications at phlebotomy and ease of draw. In lack of published data, this study aimed to establish reference intervals (RI) for correct interpretation of VBG results.MethodsOne hundred and 51 adult volunteers (101 females, 50 males 18–70 y), were enrolled after completion of a health questionnaire. Venous blood was drawn into safePICO syringes and analysed on ABL827 blood gas analyser (Radiometer Pacific Pty. Ltd.). A non-parametric approach was used to directly establish the VBG RI which was compared to a calculated VBG RI based on a meta-analysis of differences between ABG and VBGResultsAfter exclusions, 134 results were used to derive VBG RI: pH 7.30–7.43, partial pressure of carbon dioxide (pCO2) 38–58 mmHg, partial pressure of oxygen (pO2) 19–65 mmHg, bicarbonate (HCO3−) 22–30 mmol/L, sodium 135–143 mmol/L, potassium 3.6–4.5 mmol/L, chloride 101–110 mmol/L, ionised calcium 1.14–1.29 mmol/L, lactate 0.4–2.2 mmol/L, base excess (BE) −1.9–4.5 mmol/L, saturated oxygen (sO2) 23–93%, carboxyhaemoglobin 0.4–1.4% and methaemoglobin 0.3–0.9%. The meta-analysis revealed differences between ABG and VBG for pH, HCO3−, pCO2 and pO2 of 0.032, −1.0 mmol/L, −4.2 and 39.9 mmHg, respectively. Using this data along with established ABG RI, calculated VBG RI of pH 7.32–7.42, HCO3− 23 – 27 mmol/L, pCO2 36–49 mmHg (Female), pCO2 39–52 mmHg (Male) and pO2 43–68 mmHg were formulated and compared to the VBG RI of this study.ConclusionsAn adult reference interval has been established to assist interpretation of VBG results.

Are the currently used reference intervals for creatine kinase (CK) reflecting the general population? The Tromsø Study

2012 ◽  
Vol 50 (5) ◽  
Author(s):  
Hallvard Lilleng ◽  
Stein Harald Johnsen ◽  
Tom Wilsgaard ◽  
Svein Ivar Bekkelund
Keyword(s):  
Creatine Kinase ◽  
General Population ◽  
Reference Interval ◽  
Reference Intervals ◽  
Control Analysis ◽  
Age Group ◽  
Background Population ◽  
Norwegian Population ◽  
Reference Limits ◽  
Laboratory Reference

AbstractLaboratory reference intervals are not necessarily reflecting the range in the background population. This study compared creatine kinase (CK) reference intervals calculated from a large sample from a Norwegian population with those elaborated by the Nordic Reference Interval Project (NORIP). It also assessed the pattern of CK-normalization after standardized control analyses.New upper reference limits (URL) CK values were calculated after exclusion of individuals with risk of hyperCKemia and including individuals with incidentally detected hyperCKemia after they had completed a standardized control analysis. After exclusion of 5924 individuals with possible causes of hyperCKemia, CK samples were analyzed in 6904 individuals participating in the 6th survey of The Tromsø Study. URL was defined as the 97.5 percentile.New URL in women was 207 U/L. In men <50 years it was 395 U/L and in men ≥50 years 340 U/L. In individuals with elevated CK, normalization grade after control analysis was inversely correlated to the CK level (p<0.04).URL CK values in women and in men <50 years of age were in accordance with URL CK values given by the NORIP. In men ≥50 years, a higher URL was found and the findings suggest an upward adjustment of URL in this age group.

scholarly journals Reference intervals for serum lipids and prevalence of dyslipidaemia in 6–12-year-old children: The Health Oriented Pedagogical Project (HOPP)

2018 ◽  
Vol 46 (21_suppl) ◽  
pp. 21-27 ◽  
Author(s):  
Martin Frank Strand ◽  
Per Morten Fredriksen ◽  
Ole Petter Hjelle ◽  
Morten Lindberg
Keyword(s):  
Total Cholesterol ◽  
Serum Lipids ◽  
Venous Blood ◽  
Elevated Serum ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Reference Intervals ◽  
Age And Gender ◽  
Norwegian Population ◽  
And Gender

Aims: Elevated serum lipid concentrations in childhood are thought to be risk factors for the development of cardiovascular disease later in life. The present study aims to provide age- and gender-related reference intervals for total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, and non-HDL cholesterol in healthy school children. We also investigated the prevalence of dyslipidaemia using the published criteria for these biomarkers. Methods: Venous blood and anthropometric data were collected from 1340 children in the HOPP study, aged between 6 and 12 years. Age- and gender-related reference intervals (2.5th and 97.5th percentiles) were established according to the IFCC recommendations, using the software RefVal 4.10. Results: Gender differences were observed for total cholesterol and non-HDL cholesterol, but not for HDL cholesterol. Age differences were observed for total cholesterol. The reference intervals were in the range of 3.1–5.9 mmol/L for total cholesterol, 1.0–2.4 mmol/L for HDL cholesterol and 1.4–4.2 mmol/L for non-HDL cholesterol. Dyslipidaemia prevalence was as follows: increased TC 9.6%, decreased HDL 1.6%, and increased non-HDL 5.6%. Conclusions: Age- and gender-related reference intervals in a Norwegian population are similar to those reported in other countries. The prevalence of dyslipidaemia among Norwegian children is significant, emphasising the importance of appropriate reference intervals in clinical practice.

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