Age-Specific Reference Intervals for PT, aPTT, Fibrinogen and Thrombin Time for Parturient Women

Background Parturient women are healthy individuals who require special consideration. Parturient women are considered to be in a hyper-coagulable state. For example, the fibrinogen (FIB) levels are often higher than the upper limit of normal reference intervals (RIs) in parturient women than in non-parturient healthy individuals (2–4 g/L). Objective The aim of this study is to establish the RIs of pro-thrombin time (PT), activated partial thromboplastin time (aPTT), FIB levels and thrombin time (TT) for parturient women. Materials and Methods Blood levels of PT, aPTT, FIB and TT were assayed on an ACL TOP 700 automatic coagulation analyser using plasma samples from 10,472 parturient women. Outlier results were excluded by using Tukey's test. The RIs were calculated by the Clinical and Laboratory Standards Institute C28-A3 guideline. Results The RIs of PT, aPTT, FIB and TT were 8.7 to 12.1 seconds (8.7–12.2 seconds for 16–20 years old, 8.7–12.1 second for 21–25 years old, 8.6–12.0 second for 26–30 years old, 8.7–12.0 second for 31–35 years old, 8.7–12.6 second for 36–40 years old and 8.8–12.2 second for 41 years old), 22.9 to 42.3 seconds, 1.98 to 5.82 g/L and 9.9 to 16.7 seconds, respectively. PT levels were found to be positively associated with aging. Conclusion The above-established age-specific RIs, defined by using a large dataset, may assist clinicians in making accurate medical decisions. This was the first study in which the RIs of PT, aPTT, FIB and TT were established for parturient women in different age groups.

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Establishing laboratory-specific reference intervals for TSH and fT4 by use of the indirect Hoffman method

PLoS ONE ◽

10.1371/journal.pone.0261715 ◽

2022 ◽

Vol 17 (1) ◽

pp. e0261715

Author(s):

Sylwia Płaczkowska ◽

Małgorzata Terpińska ◽

Agnieszka Piwowar

Keyword(s):

Low Cost ◽

Adult Population ◽

Age Groups ◽

Large Data ◽

Reference Intervals ◽

Medical Laboratory ◽

Specific Reference ◽

Medical Decisions ◽

Indirect Methods ◽

Laboratory Information Systems

Background The results of examinations of laboratory parameters are the basis of appropriate medical decisions. The availability of reliable and accurate reference intervals (RIs) for each laboratory parameter is an integral part of its appropriate interpretation. Each medical laboratory should confirm their RIs. Up-to-date reference intervals for thyroid function hormones are still a matter of ongoing controversy. The aim of the study was the application of the indirect Hoffman method to determine RIs for TSH and fT4 based on the large data pools stored in laboratory information systems and the comparison of these RIs to generally used RIs. Material and methods The TSH and fT4 routine examination results of hospitalized and outpatient populations were collected over five years (2015–2019), and reference limits were established by the improved Hoffmann method after the exclusion of outliers. Comparative verification of established RIs was conducted with the RIs values provided by test manufacturers and literature data. Results Various RIs were observed in different age groups in the examined populations. For TSH, RIs varied between different age groups, with a narrower range of RIs in the studied adult population and a shift of both reference boundaries toward higher values in comparison to manufacturers’ data among children. RIs estimated for fT4 were very similar to the manufacturer and literature data. Conclusion Thyroid hormone levels change during a person’s lifetime and vary between sexes, but this difference does not always influence the clinical interpretation of laboratory results in the context of RIs. The use of indirect methods is justified due to the ease and low cost of their application.

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Establishing Laboratory-Specific Reference Intervals for TSH and fT4 by use of the Indirect Hoffman Method

10.21203/rs.3.rs-763059/v1 ◽

2021 ◽

Author(s):

Sylwia Płaczkowska ◽

Małgorzata Terpińska ◽

Agnieszka Piwowar

Keyword(s):

Low Cost ◽

Adult Population ◽

Age Groups ◽

Large Data ◽

Reference Intervals ◽

Medical Laboratory ◽

Specific Reference ◽

Medical Decisions ◽

Indirect Methods ◽

Laboratory Information Systems

Abstract Background: The results of examinations of laboratory parameters are the basis of appropriate medical decisions. The availability of reliable and accurate reference intervals (RIs) for each laboratory parameter is an integral part of its appropriate interpretation. Each medical laboratory should confirm their RIs. Up to date reference intervals for thyroid function hormones are still a matter of ongoing controversy. The aim of the study was application of the indirect Hoffman method to determine RIs for TSH and fT4 based on the large data pools stored in laboratory information systems, and the comparison of these RIs to generally used RIs.Material and methods: The TSH and fT4 routine examination results of a hospitalized and outpatients population over five years (2015-2019) were collected, and reference limits were established by the improved Hoffmann method after the exclusion of outliers. Comparative verification of established RIs was conducted with the RIs values provided by test manufacturers and literature data.Results: The various RIs in different age groups in examined populations were observed. For TSH RIs varied between different age groups, with a narrower range of RIs in the studied adult population, while for children, a shift of both reference boundaries toward higher values in comparison to manufacturers' data was observed. RIs estimated for fT4 were very similar to the manufacturer and literature data.Conclusion: Thyroid hormone levels change during a person's lifetime and vary between sexes, but this difference does not always influence the clinical interpretation of laboratory results in the context of RIs. The use of indirect methods is justified due to the ease and low cost of their application.

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Comparing Ethnicity-Specific Reference Intervals for Clinical Laboratory Tests from EHR Data

The Journal of Applied Laboratory Medicine ◽

10.1373/jalm.2018.026492 ◽

2018 ◽

Vol 3 (3) ◽

pp. 366-377 ◽

Cited By ~ 3

Author(s):

Nadav Rappoport ◽

Hyojung Paik ◽

Boris Oskotsky ◽

Ruth Tor ◽

Elad Ziv ◽

...

Keyword(s):

Race And Ethnicity ◽

Laboratory Tests ◽

Clinical Laboratory ◽

Local Population ◽

Reference Intervals ◽

Medical Decision ◽

Specific Reference ◽

Healthy Individuals ◽

Electronic Health Record Data ◽

Novel Approach

Abstract Background The results of clinical laboratory tests are an essential component of medical decision-making. To guide interpretation, test results are returned with reference intervals defined by the range in which the central 95% of values occur in healthy individuals. Clinical laboratories often set their own reference intervals to accommodate variation in local population and instrumentation. For some tests, reference intervals change as a function of sex, age, and self-identified race and ethnicity. Methods In this work, we develop a novel approach, which leverages electronic health record data, to identify healthy individuals and tests for differences in laboratory test values between populations. Results We found that the distributions of >50% of laboratory tests with currently fixed reference intervals differ among self-identified racial and ethnic groups (SIREs) in healthy individuals. Conclusions Our results confirm the known SIRE-specific differences in creatinine and suggest that more research needs to be done to determine the clinical implications of using one-size-fits-all reference intervals for other tests with SIRE-specific distributions.

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Age- and sex-specific reference intervals for the serum cystatin C/creatinine ratio in healthy children (0–18 years old)

Journal of International Medical Research ◽

10.1177/0300060519855575 ◽

2019 ◽

Vol 47 (7) ◽

pp. 3151-3159 ◽

Cited By ~ 2

Author(s):

Changjin Liu ◽

Jing Wen ◽

Jialin Xiang ◽

Xuhong Ouyang ◽

Yan Yang ◽

...

Keyword(s):

Cystatin C ◽

Pediatric Population ◽

Age Groups ◽

Serum Markers ◽

Reference Intervals ◽

Specific Reference ◽

Healthy Children ◽

Serum Samples ◽

Serum Cystatin C ◽

Age And Sex

Objective This study aimed to investigate serum levels of the cystatin C (CysC)/creatinine (Cr) ratio and renal serum markers (CysC, Cr, urea, and uric acid [UA]) for different ages and by sex. We also aimed to establish pediatric reference intervals for the serum CysC/Cr ratio. Methods Serum samples were collected from 4765 healthy children (0–18 years old). Serum markers of renal function were measured, and the CysC/Cr ratio of each participant was calculated and statistically analyzed. Results The renal marker CysC did not substantially change after 1 year old. Cr, urea, and UA levels generally increased with age. However, the serum CysC/Cr ratio steadily decreased with age. The CysC/Cr ratio showed significant differences in age among all age groups and varied with sex, except for in the 1 to 6-year-old groups. The overall serum CysC/Cr ratio in girls was higher than that in boys. Conclusion Reference intervals of the serum CysC/Cr ratio in the pediatric population were established. These intervals need to be partitioned by age and sex.

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Processing-independent proANP measurement for low concentrations in plasma: reference intervals and effect of body mass index and plasma glucose

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2017-0309 ◽

2017 ◽

Vol 56 (1) ◽

Author(s):

Peter D. Mark ◽

Ingrid Hunter ◽

Dijana Terzic ◽

Jens P. Goetze

Keyword(s):

Body Mass Index ◽

Body Mass ◽

Plasma Glucose ◽

Age Groups ◽

Radioactive Tracer ◽

Reference Intervals ◽

Specific Reference ◽

Regression Analyses ◽

Obesity And Diabetes ◽

Gender Specific

AbstractBackground:Decreased concentrations of pro-atrial-derived natriuretic peptides (proABP) in plasma have been associated with obesity and suggested as a predictor of type 2 diabetes. However, assays for measuring proANP are generally aimed to quantitate higher concentrations of proANP associated with cardiac disease. Therefore, we aimed to measure plasma proANP concentrations in a non-obese Scandinavian reference material and evaluate potential associations of plasma proANP with body mass index (BMI) and plasma glucose, respectively.Methods:We report an optimized processing-independent assay (PIA) for proANP in the lower concentration range. The assay was optimized by raising the amount of radioactive tracer and modifying the mixing ratio of resuspended plasma and buffer. Blood samples from a Scandinavian plasma cohort of 693 healthy subjects were then analyzed and age and gender-specific reference intervals were determined.Results:Simple linear regression analyses of proANP and both BMI and plasma glucose in fasting subjects displayed insignificant associations. Multiple regression analyses supported these findings. However, a higher median plasma concentration of proANP was noted among women <50 years compared to men, whereas no gender-specific differences were seen in other age groups.Conclusions:Our results show that in a healthy non-obese population, BMI and plasma glucose in fasting subjects do not affect plasma proANP concentrations. Our method should be considered for future studies on low proANP concentration studies, e.g. in obesity and diabetes.

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Age-, sex-, and race-related differences in myoglobin concentrations in the serum of healthy persons.

Clinical Chemistry ◽

10.1093/clinchem/26.13.1864 ◽

1980 ◽

Vol 26 (13) ◽

pp. 1864-1868 ◽

Cited By ~ 28

Author(s):

I W Chen ◽

R David ◽

H R Maxon ◽

M Sperling ◽

E A Stein

Keyword(s):

Black Women ◽

Black Men ◽

White Women ◽

Age Groups ◽

White Men ◽

Reference Intervals ◽

Creatinine Ratio ◽

Healthy Individuals ◽

Female Population ◽

Serum Myoglobin

Abstract A radioimmunoassay was used to study the relation of race, sex, and age to serum myoglobin concentrations in ostensibly healthy individuals: 75 white men, 76 white women, 75 black men, and 66 black women, ranging in age from 20 to 85 years. Mean serum myoglobin values were significantly higher in men than in women in both races (35 vs 31 microgram/L for whites and 44 vs 29 microgram/L for blacks). Black men had higher values than white men, but no corresponding difference was observed in the female population. Except for the group of black men, which consistently had the highest values for serum myoglobin, values were always higher for the older groups (greater than or equal to 50 years) than the younger, irrespective of race or sex. Serum myoglobin and age were significantly and directly correlated only among white men (r = 0.3408 p < 0.01, n = 75). If results were expressed as a myoglobin/creatinine ratio, the distinctions by race, sex, and age were partly eliminated. Reference intervals for serum myoglobin, expressed both ways, are given for different race, sex, and age groups.

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Immunoglobulin G (IgG) and IgG subclass reference intervals in children, using Optilite® reagents

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2018-0001 ◽

2018 ◽

Vol 56 (8) ◽

pp. 1319-1327 ◽

Cited By ~ 2

Author(s):

Olivier Grunewald ◽

Benjamin Lopez ◽

Séverine Brabant ◽

Stéphanie Rogeau ◽

Antoine Deschildre ◽

...

Keyword(s):

Immunoglobulin G ◽

Age Groups ◽

Reference Intervals ◽

Igg Subclasses ◽

Specific Reference ◽

Igg Subclass ◽

Serum Samples ◽

Gender Specific Differences ◽

Specific Igg ◽

Changes Over Time

Abstract Background: Immunoglobulin G (IgG) and IgG subclass assays are indicated in patients with suspected primary immunodeficiency (PID). Commercially available assays for IgG subclass determination are calibrated against various preparations, and so specific reference values are required for each of them. Using Optilite® reagents from The Binding Site Group Ltd., we sought to determine the pediatric IgG and IgG subclass reference intervals with respect to the ERM-DA470k certified reference material. Methods: Levels of IgG and IgG subclasses were analyzed in serum samples collected from a large cohort of PID-free children and adolescents. Reference intervals were calculated for previously published age groups (6–12 months, 12–18 months, 18 months–2 years, 2–3 years, 3–4 years, 4–6 years, 6–9 years, 9–12 years and 12–18 years), according to the Clinical and Laboratory Standards Institute’s C28-A3c protocol. Results: A total of 456 serum samples were analyzed. The correlation between the total IgG and the sum of the IgG subclasses was good (r2=0.96). No statistically significant gender-specific differences were observed. Our results for the changes over time in IgG and IgG subclass levels are consistent with previous reports. The differences between our lower/upper reference limits and those in the literature are probably due to variations in calibration. Conclusions: Our present results provide a reliable basis for the diagnosis of PIDs in childhood and for the accreditation of laboratories using Optilite® immunoturbidimetric reagents for IgG subclass measurement. Laboratory scientists and clinicians should be aware of the need for manufacturer-specific IgG subclass reference intervals.

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Cardiac-specific troponins in uncomplicated pregnancy and pre-eclampsia: A systematic review

PLoS ONE ◽

10.1371/journal.pone.0247946 ◽

2021 ◽

Vol 16 (2) ◽

pp. e0247946

Author(s):

Samuel Dockree ◽

Jennifer Brook ◽

Brian Shine ◽

Tim James ◽

Lauren Green ◽

...

Keyword(s):

Pregnant Women ◽

Troponin I ◽

Troponin T ◽

High Sensitivity ◽

Reference Intervals ◽

Careful Consideration ◽

Blood Levels ◽

Specific Reference ◽

Uncomplicated Pregnancy ◽

In Pregnancy

Background The risk of myocardial infarction (MI) increases during pregnancy, particularly in women with pre-eclampsia. MI is diagnosed by measuring high blood levels of cardiac-specific troponin (cTn), although this may be elevated in women with pre-eclampsia without MI, which increases diagnostic uncertainty. It is unclear how much cTn is elevated in uncomplicated and complicated pregnancy, which may affect whether the existing reference intervals can be used in pregnant women. Previous reviews have not investigated high-sensitivity troponin in pregnancy, compared to older, less sensitive methods. Methods Electronic searches using the terms “troponin I” or “troponin T”, and “pregnancy”, “pregnancy complications” or “obstetrics”. cTn levels were extracted from studies of women with uncomplicated pregnancies or pre-eclampsia. Results The search identified ten studies with 1581 women. Eight studies used contemporary methods that may be too insensitive to use reliably in this clinical setting. Two studies used high-sensitivity assays, with one reporting an elevation in troponin I (TnI) in pre-eclampsia compared to uncomplicated pregnancy, and the other only examining women with pre-eclampsia. Seven studies compared cTn between women with pre-eclampsia or uncomplicated pregnancy using any assay. Seven studies showed elevated TnI in pre-eclampsia compared to uncomplicated pregnancy or non-pregnant women. One study measured troponin T (TnT) in pregnancy but did not examine pre-eclampsia. Conclusion TnI appears to be elevated in pre-eclampsia, irrespective of methodology, which may reflect the role of cardiac stress in this condition. TnI may be similar in healthy pregnant and non-pregnant women, but we found no literature reporting pregnancy-specific reference intervals using high-sensitivity tests. This limits broader application of cTn in pregnancy. There is a need to define reference intervals for cTn in pregnant women, which should involve serial sampling throughout pregnancy, with careful consideration for gestational age and body mass index, which cause dynamic changes in normal maternal physiology.

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Reference intervals developed from data for hospitalized patients: computerized method based on combination of laboratory and diagnostic data

Clinical Chemistry ◽

10.1093/clinchem/40.12.2209 ◽

1994 ◽

Vol 40 (12) ◽

pp. 2209-2215 ◽

Cited By ~ 41

Author(s):

T Kouri ◽

V Kairisto ◽

A Virtanen ◽

E Uusipaikka ◽

A Rajamäki ◽

...

Keyword(s):

Mean Corpuscular Volume ◽

Age Groups ◽

Hemoglobin Concentration ◽

Reference Intervals ◽

Hospitalized Patients ◽

Healthy Individuals ◽

Reference Limits ◽

Health Related ◽

Final Group

Abstract We utilized the databases of a hospital information system to select for determination of reference values various individual hospitalized patients on the basis of their diagnoses at discharge. The nonparametric 2.5-97.5% "health-related" reference intervals were calculated for hemoglobin concentration, mean corpuscular volume (MCV), and erythrocyte count for both sexes. After excluding patients with diseases possibly affecting erythrocyte variables, we obtained a final group of 1786 women and 1450 men, ages 20-65 years, who were studied in age groups of 20-30, 30-45, 45-55, and 55-65 years. The upper reference limits of the MCV results obtained from hospitalized patients were higher than those produced conventionally from healthy individuals, as would be intuitively suggested by clinical experience. This method, based on selection by diagnosis, could be applicable to various analytes measured in hospital laboratories, provided sufficient data are available as databases.

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