Adult Reference Intervals Research Articles

Updated total IgE reference intervals in Norwegian adults.

It is important and expected of laboratories to provide updated reference intervals to the clinician. As no recent publications report adult total IgE reference intervals on a Scandinavian population, the aim of our study was therefore to provide an estimate on healthy Norweigian adults. A reference interval study was conducted in accordance to CLSI guidelines. Samples were collected from n = 252 presumably healthy adult participants enrolled through the regional blood donation program. Total IgE measurements were performed on the ImmunoCAPTM platform (Thermo Fisher Diagnostics) traceable to the WHO-reference standard (75/502) for total IgE measurements. An upper 95% total IgE reference limit was estimated to 302 kU/L (90% CI 177-388 kU/L), and the 97.5% percentile was estimated to 391 kU/L (90% CI 344-560 kU/L). No significant differences were found between participants who self-reported having an allergic disease and participants who did not self-report having an allergic disease. Our results and other recent publications find markedly higher values than adult reference intervals established four decades ago which still remain widely used by clinical laboratories. We therefore recommend total IgE reference intervals should be critically reviewed and updated.

The Origin of Ferritin Reference Intervals: A Systematic Review

Background: Iron-deficiency is one of the most prevalent conditions worldwide and causes significant morbidity and mortality. Iron-deficiency most commonly affects individuals of lower socio-economic status (SES). Previous research has shown that those of lower SES are both less likely to be diagnosed and treated for iron deficiency. Ferritin is an iron-storage protein that is a sensitive diagnostic marker of iron-deficiency. However, the utility of ferritin is limited due to discrepancies in the thresholds used in clinical guidelines and clinical laboratories. There is growing concern that the lower limit of "normal" ferritin is inappropriately low, particularly for females, and is underestimating and promulgating the prevalence of iron-deficiency. As such, we conducted a systematic review to evaluate the data informing ferritin reference intervals (RIs) in adults. Methods: A systematic review was conducted as per PRISMA guidelines using MEDLINE, EMBASE and CENTRAL databases from inception to November, 2021 to identify studies that reported ferritin RIs in the adult population. Additional articles were hand-selected from screening the reference lists of included studies and the first ten pages of Google Scholar in July, 2022. A search of the grey literature was also conducted using Health Canada, European Medicines Agency, and the U.S. Food and Drug Administration databases to review the manufacturer product inserts for the five most commonly used assays globally. Two reviewers screened and performed data abstraction based on the protocol submitted to PROSPERO. The objectives were to summarize the research studies on the derivation of ferritin RIs and to conduct a quality assessment based on a modified version of the Clinical and Laboratory Standards (CLSI) guidelines for establishing RIs as well as quality indicators specific to iron-deficiency. We also aimed to describe reported ferritin lower limit of normal (LLN) in general and in relevant subgroups of patients using descriptive statistics (i.e., median, range). Results: 2307 studies were screened, and 62 full texts were included. The included studies consisted of "apparently healthy individuals", but only 5 (8%) studies assessed for bleeding history/conditions, 5 (8%) for menstrual history, 7 (11%) for menopause status, 22 (35%) for pregnancy status, 9 (14%) for diet history, and 16 (25%) for iron supplementation. 36 (58%) studies measured the hemoglobin, 19 (31%) measured the mean corpuscular volume, and 22 (35%) measured inflammatory markers. For the quality of the studies, only 28 (45%) referenced a RI guideline, 21 (34%) performed outlier detection, 46 (74%) described RI calculation method, and 18 (29%) reported confidence intervals. The top 5 commercial ferritin lab assays report ferritin RIs with a median LLN of 10.5 μg/L (range: 5-13) for females and 22 μg/L (18-30) for males. One lab assay provided a ferritin RI for pre-menopausal versus post-menopausal women. The studies informing the ferritin lab assays did not explicitly exclude patients at risk of iron-deficiency and none adhered to CLSI RI establishment guidelines. 40 studies were included in the analysis of ferritin LLN in a general population which were comprised of a total of 30,474 females (20-8678 females per study) and 29,615 males (20-8913 males per study). The median ferritin LLN was 8 μg/L (0-40) in females and 27 μg/L (6-133) in males. 11 studies analyzed ferritin RIs in presumed pre- and post-menopausal females with an age threshold of 45-50 years. A median ferritin LLN of 6 μg/L (2-31) was found in pre-menopausal versus 11 μg/L (0-70) in post-menopausal females. There were 4 studies of pregnant individuals (n=1599), and we found a median ferritin LLN of 5.6 μg/L (0-9.3) among them. Conclusions: This systematic review showed that the published literature on numerous ferritin assays have a LLN well below 30 μg/L, despite robust evidence suggesting a ferritin below 30 μg/L is in keeping with clinical iron-deficiency. Data driving existing ferritin RIs appear at high risk of bias given the lack of exclusion of individuals at risk for iron-deficiency and lack of adherence to CLSI standards in the presumed "normal" sample. Therefore, we suggest adoption of evidence-based laboratory clinical decision limits to help clinicians detect and treat iron-deficiency to minimize propagation of related health inequity and medico-social injustice.

Routine clinical chemistry and haematological test reference intervals for healthy adults in the Bhutanese population.

Laboratory medicine plays a critical role in the modern healthcare system, and it is reported to influence 60-70% of clinical decision makings. The quantitative laboratory test results are interpreted by comparing to the Reference Intervals (RIs) and therefore the use of appropriate RIs is critical. Clinical laboratories in Bhutan have been randomly using RIs from textbooks and manufacturer's package inserts without even verifying their applicability and therefore lessening their contribution to clinical decision makings. To improve the healthcare service delivery in Bhutan, this study aims to establish routine clinical chemistry and haematological test RIs for healthy adults in the Bhutanese population. Out of 1150 (male, n = 570; female, n = 580) healthy Bhutanese adults listed for the study through a simple random sampling technique, 1002 (male, n = 405; female, n = 597) individuals were assessed and 815 (male, n = 372; female, n = 443) individuals were enrolled in the study. An adequate volume of venous blood was drawn from these participants with the use of standard phlebotomy technique for clinical chemistry and haematological analysis. The laboratory data were analysed with the use of statistical methods recommended by the International Federation of Clinical Chemistry and Laboratory Medicine and Clinical and Laboratory Standards Institute. After excluding the test results indicating underlying pathology and statistically detected outliers, a maximum of 775 (male, n = 346; female, n = 429) and 784 (male, n = 351; female, n = 433) individuals test values were eligible for clinical chemistry and haematology RIs establishment respectively. Statistically, there were no significant differences between age groups of same-sex for both test categories; however, significant differences between sex were observed for various test parameters in both test categories. Our RIs are generally comparable to other published literature. The established RIs are applicable to all the adult Bhutanese population; however, clinical laboratories should validate the transference of these RIs before using them for clinical purposes.

Performance evaluation of the BC-720 auto hematology analyzer and establishment of the reference intervals of erythrocyte sedimentation rate in healthy adults.

BackgroundErythrocyte sedimentation rate (ESR) is a new reporting parameter of the BC-720 auto hematology analyzer; however, no biological reference interval for healthy adults has been established for this parameter.MethodsOutpatients or hospitalized patients with ESR test orders were selected. The ESR was measured by the standard method of ESR (Westergren) recommended by the International Council for Standardization in Hematology (ICSH), the BC-720 hematology analyzer, and the LBY-XC40B auto ESR analyzer. The data were statistically analyzed and compared among different methods. The repeatability and carryover rate (CR) of the BC-720 were assessed in randomly selected samples for each range segment. Blood Samples from three hospitals in China were collected, and the reference interval of the BC-720 ESR was determined.ResultsThe ESR results measured by the BC-720 correlated well with the Westergren method (r=0.957, y = 0.359 + 1.016x), and there was no significant difference between these two methods (P>0.05). The correlation between LBY-XC40B auto ESR analyzer and Westergren was y = 1 + 1.25x and r=0.856. The BC-720 ESR has good repeatability [standard deviation (SD) ≤1 mm/h, coefficient of variation (CV) ≤5%], and the CR was less than 1%. The 95th percentile of the biological reference interval for BC-720 ESR is 15 mm/h for men and 24 mm/h for women.ConclusionsThe Mindray BC-720 ESR showed high accuracy and good repeatability, which provided a faster, safer, and more reliable method to measure ESR. The reference intervals for BC-720 ESR could guide better clinical decisions for the laboratories utilizing this new method.

Adult and neonate TSH blood spot reference intervals.

Background: Neonatal congenital hypothyroidism screening is performed by measuring thyroid-stimulating hormone (TSH) in a dried blood spot (DBS) sample, whereas acquired hypothyroidism uses serum TSH. There is no established DBS TSH reference interval, but knowing this is useful, as some patients cannot tolerate venepuncture, so DBS collection is seen as an acceptable alternative. The aim of this study was to establish DBS TSH reference intervals in adults and neonates (day 5-8), and determine the relationship between serum and DBS TSH.Methods: Euthyroid adults, not on thyroid medication and with a normal haematocrit, were selected. If they had a paired lithium heparin sample, DBS were prepared by spotting 50µL of whole blood onto filter paper. Dried blood spot TSH was measured using the PerkinElmer Neonatal hTSH kit on the GSP instrument and serum using the Abbott Architect assay. The relationship between DBS and serum TSH was analysed using Passing-Bablok regression and the adult DBS TSH reference interval calculated using transformed data. The neonatal reference interval was calculated from screening results using the non-parametric method.Results: Overall, 109 adult samples were included in the study (61 female). The Passing-Bablok regression was: DBS TSH = 0.68 × serum TSH + 0.07, and reference interval was 0.49-3.07 mU/L. The neonatal DBS reference interval was 0.40-4.10 mU/L from 8351 results.Conclusion: This study derived adult and neonate TSH DBS reference intervals using the GSP analyser and established the relationship between serum and DBS TSH. Knowing this information will allow for improved interpretation of DBS TSH results.

Blood chemistry and rectal temperature changes in a population of healthy, fall-born, suckling beef calves from birth to 72 h of age

To determine changes in suckling neonatal beef calf blood chemistry and body temperature during the first 72 h of life, jugular blood samples and rectal temperatures were obtained from 24 healthy, fall-born Angus-cross and Hereford calves (average calving date = September 11) at 0 (after standing, but pre-suckling), 6, 12, 24, 48, and 72 h postnatally. Serum chemistry panels were conducted, and plasma triglycerides and serum non-esterified fatty acids (NEFA) were also determined. Data were analyzed using sampling hour as a repeated effect, and individual data points were compared to adult bovine reference intervals. All serum chemistry measures were affected by hour of age except bicarbonate (P = 0.48). Serum glucose, total protein, and globulin concentrations increased (P < 0.001) from 0 to 24 h. Plasma triglycerides increased (P < 0.001) from 0 to 6 h and 24 to 72 h. Serum urea nitrogen increased (P < 0.001) from 0 to 6 h and decreased (P = 0.01) from 48 to 72 h. Serum NEFA and creatine kinase (CK) increased (P < 0.001) from 0 to 6 h, but decreased (P ≤ 0.02) from 12 to 72 h. Serum magnesium, aspartate aminotransferase (AST), and total and direct bilirubin increased (P < 0.001) during the first 12 h, then decreased (P < 0.001) from 24 to 72 h. Gamma-glutamyl transpeptidase (GGT) increased (P < 0.001) from 0 to 12, and then decreased (P < 0.003) from 12 to 48 h. Serum creatinine decreased (P < 0.001) from 0 to 72 h, and albumin decreased (P < 0.01) from 0 to 12 h but increased (P < 0.001) from 24 to 48 h. Anion gap decreased (P ≤ 0.05) from 6 to 24 h. No serum components measured were within adult bovine reference intervals for all calves at all sampling times. All serum albumin concentrations were outside of reference intervals, and the majority of serum glucose, calcium, phosphorus, potassium, CK, GGT, and total bilirubin were outside of reference intervals. More serum chemistry measures diverged from reference intervals in the first 24 h of neonatal life. Rectal temperature decreased (P = 0.003) from 0 to 6 h of age, then increased (P ≤ 0.02) from 12 to 48 h. In summary, blood chemistry profiles of healthy, suckling neonatal beef calves change over the first 72 h of life, indicating rapid changes in metabolism and physiology. Bovine reference intervals based on adults do not appear to represent neonatal calves; thus, neonatal status and animal age should be taken into consideration when interpreting serum chemistry in a clinical or research setting.

Cord-Blood Derived Chemistry Reference Values in Preterm Infants for Sodium, Chloride, Potassium, Glucose, and Creatinine.

International guidelines recommend that preterm infants should be supported to maintain their serum electrolytes within "normal" ranges. In term babies, cord blood values differed in pathological pregnancies from healthy ones. We examined cord blood sodium, chloride, potassium, glucose, and creatinine to derive maturity-related reference intervals. We examined associations with gestational age, delivery mode, singleton versus multiple, and prenatal maternal adverse conditions. We compared preterm cord values to term, and to adult reference ranges. There were 591 infants, 537 preterm and 54 term. Preterm cord glucose levels were steady (3.7 ± 1.1 mmol/L), while sodium, chloride, and creatinine increased over GA by 0.17, 0.14 mmol/L/week, and 1.07 µmol/L/week, respectively (p < 0.003). Average preterm cord potassium and chloride were higher than the term (p < 0.05). Compared with adult reference intervals, cord preterm reference intervals were higher for chloride (100-111 vs. 98-106 mmol/L), lower for creatinine (29-84 vs. 62-115 µmol/L), and more variable for potassium (2.7-7.9 vs. 3.5-5.0 mmol/L) and sodium (130-141 vs. 136-145 mmol/L). Cesarean section was associated with higher potassium and lower glucose, multiple births with higher chloride and creatinine and lower glucose, and SGA with lower glucose. Cord blood values varied across the GA range with increases in sodium, chloride, and creatinine, while glucose remained steady. Average preterm reference values were higher than term values for potassium and chloride. Preterm reference values differed from published adults' reference values. The changes across GA and by delivery mode, SGA, and being a multiple, which may have direct implications for neonatal care and fluid management. · Cord blood electrolyte, creatinine, and glucose values vary across neonatal gestational age.. · Average preterm cord values of potassium and chloride were higher than term values.. · Cord reference values differ by delivery mode, growth, and multiple impacting neonatal care decisions..

Reference interval for urinary neutrophil gelatinase-associated lipocalin in healthy adults in Jiangsu region in Eastern China: amulticenter study.

Aim: We explored the concentrations of urinary neutrophil gelatinase-associated lipocalin (NGAL) in healthy adults in the Jiangsu region in Eastern China and established a reference interval using latex-enhanced immunoturbidimetry to provide important guidelines for the interpretation and application of urinary NGAL in clinical practice. Methods: In total, 1970 eligible subjects from four regions were included in this study. The urinary NGAL levels were measured using an AU5800 automatic biochemical analyzer with its matched reagents. The urinary NGAL reference interval was established using the one-sided percentile method (95th percentile). Results: The urinary NGAL data were non-normally distributed. The urinary NGAL levels were not significantly different by sex or age. Therefore, the urinary NGAL reference interval in healthy adults in the Jiangsu region in Eastern China was <87.5ng/ml (95th percentile of the upper limit). Conclusion: Urinary NGAL reference interval will play an important role in promoting the clinical value of urinary NGAL.

Reference interval for type III procollagen (PIIINP) using the Advia centaur PIIINP assay in adults and elderly

Objective The amino-terminal peptide of type III procollagen (PIIINP) is a byproduct of type III collagen synthesis that exhibits promise as a biomarker of fibrosis, specifically in monitoring hepatic fibrosis in methotrexate treated patients. The Advia Centaur® PIIINP assay is developed for track-based automated laboratory systems and is suitable for large volume analysis. Reference intervals in children and younger adults have been published previously. Here we measured PIIINP to determine reference ranges, specifically including elderly patients, for whom such are currently lacking. Methods Samples were collected from subjects ranging from 20 to 98 years of age. Blood donors and clinical samples from primary care patients were used for reference interval calculation. Samples were analysed using the Advia Centaur® PIIINP assay. After exclusion of samples high in alanine transaminase (AST), aspartate transaminase (ALT), and C-reactive protein (CRP) 386 samples were used in the reference interval calculation. Results and conclusion We determined the following reference interval for the Advia Centaur® PIIINP assay: the lower limit of the reference interval (2.5% percentile with 95% CI) was 4.42 (4.20–4.65) µg/L and the upper limit of the reference interval (97.5% percentile 95% CI) 16.0 (15.04–17.02) µg/L.No significant differences in mean PIIINP concentrations were found between men and women. While differing mean PIIINP concentrations were seen among subjects in different age groups, the differences were small and partitioning of reference range was determined not to be necessary.

Symmetric dimethylarginine concentrations in healthy neonatal foals and mares.

BackgroundSymmetric dimethylarginine (SDMA) is a renal biomarker correlated with glomerular filtration rate (GFR).ObjectivesDescribe changes in SDMA in clinically healthy foals and their mares during the first month postfoaling.AnimalsConvenience sampling of healthy periparturient Thoroughbred mares and their full‐term foals from a population of client‐owned horses.MethodsSerum and EDTA whole blood samples were collected from mares in their last month of pregnancy and then from mares and foals at approximately <12 hours, 48 hours, 7 days, and 30 days postbirth. Samples were processed at a commercial reference laboratory for CBC and serum biochemistry, including SDMA concentrations.ResultsA total of 125 foals and 104 mares were included. Upper limits for SDMA concentrations in foals were above the adult horse reference interval for the first 20 or more days of life. Median SDMA concentrations decreased from 70 μg/dL (range, 7‐100 μg/dL) to 18 μg/dL (range, 6‐27 μg/dL) during the first 3 to 4 weeks of life. At birth, the SDMA concentration reference range was established as 0 to 100 μg/dL (upper limit of the assay); 0 to 85 μg/dL for 1 to 4 days old, 0 to 36 μg/dL for 5 to 10 days old, and 0 to 24 μg/dL for 20 to 30 days old. The upper reference limits for SDMA concentrations in mares did not differ from the general reference interval for adult horses. No correlation was identified between mare and foal SDMA concentrations (ρ = .06, P = .58).Conclusions and Clinical ImportanceFoal SDMA concentrations remained higher than the upper limit of the adult reference range and foals require a different reference range dependent on age.

Distribution of HOMA-IR in a population-based cohort and proposal for reference intervals.

Insulin resistance (IR) is a hallmark of type 2 diabetes mellitus (DM). The homeostatic model assessment of insulin resistance (HOMA-IR) provides an estimate for IR from fasting glucose and insulin serum concentrations. The aim of this study was to obtain a reference interval for HOMA-IR for a specific insulin immunoassay. The Gutenberg Health Study (GHS) is a population-based, prospective, single-center cohort study in Germany with 15,030 participants aged 35-74years. Fasting glucose, insulin, and C-peptide were available in 10,340 participants. HOMA-IR was calculated in this group and three reference subgroups with increasingly more stringent inclusion criteria. Age- and sex-dependent distributions of HOMA-IR and reference intervals were obtained. In a substudy three insulin assays were compared and HOMA-IR estimated for each assay. Among the 10,340 participants analyzed there were 6,590 non-diabetic, 2,901 prediabetic, and 849 diabetic individuals. Median (interquartile range [IQR]) HOMA-IR was 1.54 (1.13/2.19), 2.00 (1.39/2.99), and 4.00 (2.52/6.51), respectively. The most stringently selected reference group consisted of 1,065 persons. Median (IQR) HOMA-IR was 1.09 (0.85/1.42) with no significant difference between men and women. The 97.5th percentile was 2.35. There was a non-significant trend towards higher values with older age. Comparison of three immunoassays for insulin showed an unsatisfactory correlation among the assays and systematic differences in calculated HOMA-IR. We present HOMA-IR reference intervals for adults derived by more or less stringent selection criteria for the reference cohort. In addition we show that assay specific reference intervals for HOMA-IR are required.

Comparisons of hematologic results for juvenile versus adult shelter dogs presented for ovariohysterectomy or castration.

To compare hematologic results for juvenile versus adult dogs from shelters that outwardly appeared healthy and were presented for ovariohysterectomy or castration. 138 dogs from 13 regional shelters. Each dog underwent a physical examination (including use of a flea comb), age estimation by dental eruption characteristics, PCV, CBC, and tests for Dirofilaria immitis antigen and Anaplasma phagocytophilum, Borrelia burgdorferi, and Ehrlichia canis antibodies. Additional diagnostic tests were performed as needed. Dogs were grouped by age as < 3, ≥ 3 to ≤ 6, or > 6 months of age, with dogs ≤ 6 months of age considered juveniles and dogs > 6 months of age considered adults. Hematologic results were compared across groups. There were 138 dogs, of which 56 were juveniles (34 dogs < 3 months old; 22 dogs ≥ 3 to ≤ 6 months old) and 82 were adults. Juvenile (vs adult) dogs had lower mean calculated Hct and mean PCV whether dogs with infectious agents or parasites were included or excluded. The mean PCV and mean cell hemoglobin concentration were lower and the reticulocyte count higher for juvenile dogs < 3 months old (35.8%, 33.1 g/dL, and 135,000 reticulocytes/μL) versus adults (44.9%, 34.7 g/dL, and 68,500 reticulocytes/μL). Most (98.6%) dogs underwent surgery as scheduled; 2 dogs had surgery postponed because of thrombocytopenia or parvovirus infection. Our findings indicated that outwardly healthy-appearing juvenile shelter dogs often have results for PCV and calculated Hct that are lower than those for adult shelter dogs and adult dog reference intervals but rarely require postponement of ovariohysterectomy or castration.

Distribution of urinary N-acetyl-beta-D-glucosaminidase and the establishment of reference intervals in healthy adults.

BackgroundUrinary N‐acetyl‐beta‐D‐glucosaminidase (NAG) plays an important role in the early diagnosis and progression of diseases related to renal tubular injury. We detected the urinary NAG concentration, assessed the preliminary statistics of its distribution, and established reference intervals for healthy adults in China using the rate method.MethodsA total of 1,095 reference individuals (aged 20 to 79 years) met the requirements for inclusion in this study. Urinary NAG concentrations were detected using an AU5800 automatic biochemical analyzer with its matched reagents. The Kolmogorov‐Smirnov test was used to analyze the normality of the data. According to the guidelines of C28‐A3 and WS/T 402‐2012, the reference intervals of urinary NAG were established using the nonparametric percentile method (unilateral 95th percentile).ResultsThe urinary NAG data showed a non‐normal distribution. The distribution of urinary NAG was significantly different by sex and age. Therefore, the reference intervals of urinary NAG were established using the rate method: males (aged 20–59 years) <19.4 U/L (90% CI: 18.0–20.3 U/L); males (aged 60–79 years) <22.3 U/L (90% CI: 20.2–22.6 U/L); females (aged 20–59 years) <15.7 U/L (90% CI: 15.2–16.5 U/L); and females (aged 60–79 years) <21.4 U/L (90% CI: 20.3–22.3 U/L).ConclusionsWe established preliminary reference intervals of urinary NAG for healthy adults in China to provide guidance for health screening, auxiliary diagnosis, and treatment monitoring of renal tubule‐related diseases.

Reference intervals of common clinical biochemistry analytes in young Nigerian adults.

Reference intervals are assessment tools for interpretation of clinical test results. These intervals describe the dispersion of test parameter values of apparently healthy persons in defined populations as health status indicators. Using reference intervals obtained and validated in populations outside the geographical region of derivation for medical decision-making may impact negatively on clinical interpretation and patient management. Many countries have established their reference values, current studies on these data for Nigeria are however scarce. Determination of clinical biochemistry reference intervals for young Nigerian adults which is of particular importance in routine clinical management and conduct of clinical trials in response to existing and emerging diseases will add significantly to the existing body of knowledge. The objective was to establish reference intervals for 24biochemistry analytes among Nigerians aged 18 to 26 years. This was a cross-sectional study among 7,797 consenting male and female military applicants aged 18 to 26 years from 37 States of Nigeria. It was a total study among volunteers for military service. Blood samples were collected and subjected to serological testing for HIV-1 and 2, hepatitis-B, malaria, pregnancy and haematuria to restrict our study population to apparently healthy participants. Biochemical assays were performed on 6,169 participant samples that met the inclusion criteria. Generated data was entered into MS Excel® and exported into SPSS® software version 16 for analysis. Statistical tools used were frequencies, median, mid 95th percentile range with 2.5th and 97.5th percentiles as limits. Reference intervals were estimated using nonparametric methods. No intergender statistical comparison was made. Complete records were obtained for 6,169 eligible participants. Median values and associated reference intervals were similar in both genders. The findings from this study will help in clinical decision-making and play a significant role in supporting the current global rapid expansion of clinical trials in response to the urgent need for preventive and therapeutic solutions to existing and emerging diseases.

Establishment of Pediatric Reference Intervals for Routine Laboratory Tests in Korean Population: A Retrospective Multicenter Analysis.

BackgroundReference intervals defined for adults or children of other ethnicities cannot be applied in the evaluation of Korean pediatric patients. Pediatric reference intervals are difficult to establish because children are in their growing stage and their physiology changes continuously. We aimed to establish reference intervals for routine laboratory tests for Korean pediatric patients through retrospective multicenter data analysis.MethodsPreoperative laboratory test results from 1,031 pediatric patients aged 0 month–18 years who underwent minor surgeries in four university hospitals were collected. Age- and sex-specific reference intervals for routine laboratory tests were defined based on the Clinical and Laboratory Standards Institute (CLSI) EP28-A3c guidelines.ResultsThe pediatric reference intervals determined in this study were different from existing adult reference intervals and pediatric reference intervals for other ethnicities. Most tests required age-specific partitioning, and some of those required sex-specific partitioning for at least one age-partitioned subgroup. Erythrocyte sedimentation rate, monocyte percentage, basophil percentage, activated partial thromboplastin time, glucose, cholesterol, albumin, bilirubin, chloride, and C-reactive protein did not show any difference between age- or sex-partitioned subgroups.ConclusionsWe determined Korean pediatric reference intervals for hematology, coagulation, and chemistry tests by indirect sampling based on medical record data from multiple institutions. These reference intervals would be valuable for clinical evaluations in the Korean pediatric population.

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.

Simple SummaryTo define a healthy animal in an experimental setting or to differentiate and backup a diagnosis in cattle practice, reference intervals (RIs) in haematology diagnostics are necessary. The RIs in calves for blood cell counts, such as platelets and white blood cells, differ from RIs in adult cattle and are not widely studied. Blood results from dairy calves in the Netherlands were used to study the variation in platelet counts in young calves and to calculate an RI for platelet and white blood cell counts. In new-born calves up to six days of age, platelet counts were lower than in calves older than five days. From six days of age until 60 days of age we propose an RI platelet count of 287–1372 × 109/L and for the first 60 days of life an RI for leukocyte count of 4.0–18.9 × 109/L.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.

Determination of a Beckman Coulter AU turbidometric method-specific caeruloplasmin reference interval.

Method-dependent variation of caeruloplasmin measurement is significant and necessitates the requirement for assay-specific reference intervals. Local determination becomes necessary in the absence of suitable published or manufacturer-quoted reference intervals. Applicability of the Beckman Coulter AU-quoted reference interval was determined by assay of 20 surplus serum samples from patients attending the medical renal stones clinic at University Hospital Southampton. Subsequently, 60 additional samples were collected for local reference interval determination. Samples were analysed for caeruloplasmin using the Beckman Coulter AU turbidometric kit on an AU680 analyser. Outliers were removed, and non-parametric rank analysis of the results was performed. The Beckman Coulter-quoted reference interval of 200-600 mg/L was unsuitable with 40% of the verification samples falling below 200 mg/L. A caeruloplasmin reference interval of 150-320 mg/L was established. Users should be aware the quoted Beckman Coulter AU turbidometric reference interval may not be appropriate. We have established a method-specific adult reference interval for routine use.

Application of the TML method to big data analytics and reference interval harmonization

Abstract Significant variation in reported reference intervals across healthcare centers and networks for many well-standardized laboratory tests continues to exist, negatively impacting patient outcomes by increasing the risk of inappropriate and inconsistent test result interpretation. Reference interval harmonization has been limited by challenges associated with direct reference interval establishment as well as hesitancies to apply currently available indirect methodologies. The Truncated Maximum Likelihood (TML) method for indirect reference interval establishment developed by the German Society of Clinical Chemistry and Laboratory Medicine (DGKL) presents unique clinical and statistical advantages compared to traditional indirect methods (Hoffmann and Bhattacharya), increasing the feasibility of developing indirect reference intervals that are comparable to those determined using a direct a priori approach based on healthy reference populations. Here, we review the application of indirect methods, particularly the TML method, to reference interval harmonization and discuss their associated advantages and disadvantages. We also describe the CSCC Reference Interval Harmonization Working Group’s experience with the application of the TML method in harmonization of adult reference intervals in Canada.

Haematological reference intervals for healthy adults in Bamenda, Cameroon.

BackgroundIn the era of evidence-based medicine, haematological reference intervals are essential for the interpretation of data for clinical decision-making, monitoring of treatment and research. It is not uncommon that reference intervals used in most African countries have been obtained from published scientific literature, textbooks, reagent/instrument manuals.ObjectiveThe aim of this study was to determine haematological reference intervals of healthy adults in Bamenda, Cameroon.MethodsThis was a cross-sectional study conducted between June and November 2015. Participants were voluntary blood donors at the Blood Bank Service of the Regional Hospital Bamenda aged between 18 and 65 years. The mean, median and standard deviation of the mean were calculated for each haematological parameter. The 95th percentile reference intervals were determined using the 2.5th and 97.5th percentile. The differences between gender for all the parameters were evaluated using the Kruskal-Wallis test. Significance was determined at the 95% confidence level.ResultsOut of a total of 340 participants, 202 (59.4%) were men and 138 (40.6%) were women. The median red blood cell, haemoglobin, haematocrit and mean cell haemoglobin concentration were significantly higher in men than women (p < 0.001). The median white blood cell, absolute lymphocytes count, absolute granulocytes and platelet counts for men were significantly lower than those for women (p < 0.011).ConclusionWe propose that the present established haematological reference intervals in this study should be used for clinical management of patients and interpretation of laboratory data for research in Bamenda.

Reference intervals for venous blood gas measurement in adults.

Venous 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. One hundred and 51 adult volunteers (101 females, 50 males, 18-70years) 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 VBG. After exclusions, 134 results were used to derive VBG RI: pH 7.30-7.43, partial pressure of carbon dioxide (pCO2) 38-58mmHg, partial pressure of oxygen (pO2) 19-65mmHg, bicarbonate (HCO3-) 22-30mmol/L, sodium 135-143mmol/L, potassium 3.6-4.5mmol/L, chloride 101-110mmol/L, ionised calcium 1.14-1.29mmol/L, lactate 0.4-2.2mmol/L, base excess (BE)-1.9-4.5mmol/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,-1.0mmol/L,-4.2 and 39.9mmHg, respectively. Using this data along with established ABG RI, calculated VBG RI of pH 7.32-7.42, HCO3- 23- 27mmol/L, pCO2 36-49mmHg (female), pCO2 39-52mmHg (male) and pO2 43-68mmHg were formulated and compared to the VBG RI of this study. An adult reference interval has been established to assist interpretation of VBG results.