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Clinical Pathology

Comparison of Five Common Analyzers in the Measurement of Chemistry Analytes in an Authentic Cohort of Body Fluid Specimens

Abstract

Objectives

Interpretation of body fluid (BF) results is based on published studies and clinical guidelines. The aim of this study is to determine whether the assays from five common commercial vendors produce similar results in BFs for 12 analytes in a BF cohort.

Methods

BFs (n = 25) and serum (n = 5) were analyzed on five instruments (Roche cobas c501, Ortho 5600, Beckman AU5800 and DXI800, Siemens Vista 1500, and Abbott Architect c8000) to measure albumin, amylase, total bilirubin, cholesterol, creatinine, glucose, lactate dehydrogenase (LDH), lipase, total protein, triglycerides, urea nitrogen, and carcinoembryonic antigen. Deming regression and Bland-Altman analysis were used for method comparison to Roche.

Results

Results were significantly different from Roche for LDH and lipase on Ortho and lipase on Siemens but similar for both BFs and serum. BF differences were larger than serum differences when measuring creatinine, glucose, and urea nitrogen on Ortho and glucose on Siemens.

Conclusions

Five instruments used to perform BF testing produce results that are not significantly different except for lipase and LDH measurements. Bias of similar magnitude observed in both BF and serum should not affect interpretation. Further investigations into Ortho and Siemens measuring glucose and Ortho measuring creatinine and urea nitrogen are warranted.

Key Points

  • Twelve analytes measured in body fluids were compared among five different instruments to determine if method differences existed that could affect interpretation.

  • Lactate dehydrogenase and lipase results differed significantly between instruments but were similar in magnitude for serum and body fluids, thereby not affecting interpretation.

  • Some instruments displayed bias in body fluid not observed in serum for glucose, creatinine, and urea nitrogen, suggesting discretion may be warranted.

Introduction

Clinical laboratories provide a valuable service when performing testing on alternate specimen types such as pleural, synovial, peritoneal, and drain fluids. These specimens are submitted to establish, narrow, and confirm a diagnosis in patients with pathologic effusions. The interpretation of results is often made in comparison to measurement in serum, compared with expected concentrations of the analyte in serum, or using an absolute concentration as a decision limit above or below, which is considered positive or negative for a particular condition. Laboratories offering this testing on a routine basis are challenged to provide interpretations in the information system to assist with result interpretation and clinical decision making. Numerous studies have been published dating back to the 1970s to establish the usefulness of measuring analytes in body fluids (BFs), but based on the paucity of method description and age of some of these studies, laboratories are challenged to confidently transfer the decision limits into use.1 The aim of this study is to determine whether the assays from five common commercial vendors produce similar results in a cohort of BFs and serum for 11 common chemistry analytes (albumin, amylase, total bilirubin, cholesterol, creatinine, glucose, lactate dehydrogenase [LDH], lipase, total protein, triglycerides, urea nitrogen) and carcinoembryonic antigen (CEA).

In total, 117 remnant BFs after clinical testing was completed were collected over 30 days from Mayo Clinic Central Clinical Laboratory in Rochester, MN (IRB 18-007287). Fluid types consisted of amniotic (n = 2), drain (n = 18), pericardial (n = 3), peritoneal (n = 54), peritoneal dialysate (n = 3), pleural (n = 33), and synovial (n = 4). A cohort of serum samples (n = 31) was also analyzed as a normative analytical control between instruments and methods for an approved sample type. Specimens were aliquoted into four tubes and shipped frozen overnight to each study site except for specimens requiring analysis of LDH, which were gathered over 2 days and shipped at room temperature. Specimens tested for bilirubin were protected from light. Viscous synovial fluids were pretreated with hyaluronidase according to Block et al.2

The multisite study consisted of four tertiary care health systems and five diagnostic instruments. Measurement of BF chemistries was performed at Mayo Clinic Rochester by use of the Roche cobas c501, the University of North Carolina at Chapel Hill by use of the Ortho 5600 (Ortho Clinical Diagnostics), Atrium Health in Charlotte North Carolina by use of the Beckman AU5800, and the Minneapolis Veterans Affairs Hospital by use of the Siemens Vista 1500 (Siemens Medical Solutions) and Abbott Architect c8000. CEA was measured at Mayo Clinic Rochester and Atrium Health on the Beckman Coulter DXI and compared with the other listed instruments Table 1.

Specimens were frozen until shipped to each site on the same day. Upon receipt, LDH was measured, and all frozen samples were stored 2 weeks until testing could be completed at the same time at each site. Frozen samples were prepared for testing first by equilibration to room temperature on a sample rocker for 30 minutes, followed by centrifugation at 3,500 rpm for 5 minutes prior to testing. All measurements for an analyte were tested on the same day by four methods and compared with Roche results obtained prior to freezing.

MATERIALS AND METHODS

Cohort of BF Specimens

Table 1 summarizes the methodology, traceability, measuring range, and representative reference interval for serum for each of the five instruments. Specimens were analyzed according to the manufacturer’s standard protocols for each instrument. Each analyte had 25 BFs (except LDH had 22) and five serum samples measured (Supplemental Table 1 specifies BFs tested for each analyte; all supplemental materials can be found at American Journal of Clinical Pathology online). All instruments used a valid serum calibration and acceptable quality control according to standard laboratory practices. Results below the manufacturer’s analytical measuring range were excluded for analysis.

Diagnostic Instruments and Assays

Results were compiled in Microsoft Excel. Deming regression analysis was performed for each instrument using Roche as the arbitrary reference value using EP Evaluator (Data Innovations) to calculate slope, intercept, r, and bias. Bland-Altman plots were created in OriginPro (OriginLab). Statistical analysis was accomplished using one-way analysis of variance (ANOVA) pairwise comparison of instruments, which used a Holm correction to control the type I error rate for the multiple comparisons with P < .05 considered statistically significant. The intraclass correlation coefficients (ICCs) were also calculated to quantify how consistent the values were between Roche and each of the other four methods using R software (R Foundation for Statistical Computing). Mean difference (method – Roche) and percent difference (method – Roche) / Roche × 100% and standard deviations were calculated to compare disproportionate differences between specimen types for creatinine, glucose, and urea nitrogen.

Table 1

Summary of Method Details for Analytes and Instruments Included in This Study

Analyte Abbott Architect c8000 Beckman AU5800 Ortho Vitros 5600 Roche cobas c501 Siemens Vista 1500
Amylase, U/L           
 Method  Enzymatic substrate CNPG3  Enzymatic substrate CNPG3  Enzymatic substrate amylopectin  Enzymatic substrate ethylidene-G7-PNP  Enzymatic substrate CNPG3 
 Traceability  NA  Absorptivity of CNPG3  NA  IFCC  IFCC 
 Measuring range  3-6,554  10-2,000  30-1,200  3-1,400  2-650 
 Reference interval  25-125  20-103  30-110  28-100  25-115 
Albumin, g/dL           
 Method  Bromocresol green  Bromocresol green  Bromocresol green  Bromocresol green  Bromocresol purple 
 Traceability  ERM-DA 470  ERM-DA 470K  NIST SRM 927  CRM 470  CRM 470 
 Measuring range  0.4-10.5  1.5-6.0  1.0-6.0  0.3-6.0  0.1-8.0 
 Reference interval  3.5-5.2  F: 3.7-5.3
M: 3.5-5.7 
3.5-5.0  3.5-5.2  3.4-5.0 
Bilirubin, total, mg/dL           
 Method  Diazonium salt/diazonium ion with blank  Diazonium salt/diazonium ion with blank  Diazonium salt–dyphylline  Diazonium salt/diazonium ion with blank  Diazo-caffeine/benzoate coupling (Jendrassik-Grof) with blank 
 Traceability  NIST SRM 916  Jendrassik-Grof method  NIST SRM 916  Doumas method  NIST SRM 916 
 Measuring range  0.1-25.0  0.0-30.0  0.1-27.0  0.2-30.0  0.1-25.0 
 Reference interval  0.2-1.2  0.3-1.0  0.1-1.2  0.2-1.2  0.2-1.0 
  Centaur XP  DXI       
CEA, ng/mL           
 Method  Sandwich IA mouse anti-CEA mAb  Paramagnetic, Chemilumin IA-2 mouse anti-CEA mAb (DXI 800)  Sandwich IA mouse anti-CEA mAb    Sandwich IA mouse anti-CEA mAb 
 Traceability  First international preparation 73/601  NA  First international preparation 73/601    Internal standards 
 Measuring range  0.5-1,500  0.7-850 Mayo
0.1-1,000 Atrium 
0.5-400    0.5-100 
 Reference interval  <5.0  <5.0  0.5-5.0    <5.0 
Cholesterol, mg/dL           
 Method  Enzymatic  Enzymatic  Enzymatic  Enzymatic  Enzymatic 
 Traceability  Total cholesterol verification set  NIST SRM 1951 b  NIST SRM 911  IDMS  NIST SRM 911 
 Measuring range  7-705  25-700  50-325  10-750  50-600 
 Reference interval  NCEP and the National Lipid Association         
Creatinine, mg/dL           
 Method  Enzymatic  Kinetic alkaline picrate (Jaffe reaction)  Enzymatic  Enzymatic  Enzymatic 
 Traceability  NIST SRM 914  NIST SRM 967a/IDMS  IDMS  IDMS  NIST SRM 914/IDMS 
 Measuring range  0.1-40  0.2-25.0  0.15-14.0  0.1-23.0  0.1-20.0 
 Reference interval (male)  0.7-1.2   0.7-1.3  0.70-1.30a  0.74-1.35a  0.67-1.17 
Glucose, mg/dL           
 Method  Hexokinase G6PDH/UV  Hexokinase G6PDH/UV  Oxidase, colorimetric  Hexokinase G6PDH/UV  Hexokinase G6PDH/UV 
 Traceability  NIST SRM 965  NIST SRM 965b  NIST SRM 917  IDMS  NIST SRM 917 
 Measuring range  5-800  10-800  20-625  2-675  1-500 
 Reference interval  American Diabetes Association Guidelines         
LDH, U/L           
 Method  Lactate → pyruvate  Lactate → pyruvate  Pyruvate → lactate  Lactate → pyruvate  Lactate → pyruvate 
 Traceability  IFCC  Molar absorptivity of NADH  NA  IFCC  IFCC 
 Measuring range  10-3,333  25-1,200  100-2,150  10-900  6-1,000 
 Reference interval  125-220  140-271  338-610  F: 135-214
M: 135-225 
F: 84-246
M: 87-241 
Lipase, U/L           
 Method  Enzymatic colorimetric substrate 1,2 diglyceride, quinone dye  Enzymatic colorimetric substrate 1,2 diglyceride, quinone dye  Enzymatic colorimetric substrate 1-oleoyl-2,3-diacetylglycerol  Enzymatic colorimetric substrate 1,2 diglyceride, quinine dye (Sekisui Diagnostics)  Enzymatic colorimetric substrate DGGR, methylresorufin dye 
 Traceability  NA  NA  NA  NA  NA 
 Measuring range  4-1,200    10-2,000  10-750  10-1,500 
 Reference interval  8-78  11-82  44-232 a  13-60a  73-393 
Total protein, g/dL           
 Method  Biuret  Biuret  Biuret  Biuret  Biuret 
 Traceability  NIST SRM 927  NIST SRM 927d  NIST SRM 927  NIST SRM 927  NIST SRM 927 
 Measuring range  0.8-18.4  3.0-12.0  2.0-11.0  0.5-12.0  0.1-12.0 
 Reference interval  6.4-8.3  6.4-8.9  6.5-8.3a  6.6-8.7  6.4-8.2 
Triglycerides, mg/dL           
 Method  Enzymatic glycerol phosphate oxidase without blank  Enzymatic glycerol phosphate oxidase without blank  Enzymatic colorimetric without blank  Enzymatic glycerol phosphate oxidase without blank  Enzymatic glycerol phosphate oxidase without blank 
 Traceability  ACS grade glycerol  NIST SRM 1951b  NIST SRM1951  IDMS  ACS grade glycerol 
 Measuring range  7-1,420  10-1,000  10-525  10-775  2-1,000 
 Reference interval  NCEP and the National Lipid Association         
Urea nitrogen, mg/dL           
 Method  Urease with glutamate dehydrogenase coupled enzymes  Urease with glutamate dehydrogenase coupled enzymes  Urease quinolinium dye  Urease with glutamate dehydrogenase coupled enzymes  Urease with glutamate dehydrogenase coupled enzymes 
 Traceability  NIST SRM 912  NIST SRM 909b  NIST SRM 912  NIST SRM 912  NIST SRM 912 
 Measuring range  2-125  2-130  2-120  2-100  1-150 
 Reference interval  F: 7.0-18.7
M: 8.9-20.6 
7-25  7-21a  6-20  7-18 
Analyte Abbott Architect c8000 Beckman AU5800 Ortho Vitros 5600 Roche cobas c501 Siemens Vista 1500
Amylase, U/L           
 Method  Enzymatic substrate CNPG3  Enzymatic substrate CNPG3  Enzymatic substrate amylopectin  Enzymatic substrate ethylidene-G7-PNP  Enzymatic substrate CNPG3 
 Traceability  NA  Absorptivity of CNPG3  NA  IFCC  IFCC 
 Measuring range  3-6,554  10-2,000  30-1,200  3-1,400  2-650 
 Reference interval  25-125  20-103  30-110  28-100  25-115 
Albumin, g/dL           
 Method  Bromocresol green  Bromocresol green  Bromocresol green  Bromocresol green  Bromocresol purple 
 Traceability  ERM-DA 470  ERM-DA 470K  NIST SRM 927  CRM 470  CRM 470 
 Measuring range  0.4-10.5  1.5-6.0  1.0-6.0  0.3-6.0  0.1-8.0 
 Reference interval  3.5-5.2  F: 3.7-5.3
M: 3.5-5.7 
3.5-5.0  3.5-5.2  3.4-5.0 
Bilirubin, total, mg/dL           
 Method  Diazonium salt/diazonium ion with blank  Diazonium salt/diazonium ion with blank  Diazonium salt–dyphylline  Diazonium salt/diazonium ion with blank  Diazo-caffeine/benzoate coupling (Jendrassik-Grof) with blank 
 Traceability  NIST SRM 916  Jendrassik-Grof method  NIST SRM 916  Doumas method  NIST SRM 916 
 Measuring range  0.1-25.0  0.0-30.0  0.1-27.0  0.2-30.0  0.1-25.0 
 Reference interval  0.2-1.2  0.3-1.0  0.1-1.2  0.2-1.2  0.2-1.0 
  Centaur XP  DXI       
CEA, ng/mL           
 Method  Sandwich IA mouse anti-CEA mAb  Paramagnetic, Chemilumin IA-2 mouse anti-CEA mAb (DXI 800)  Sandwich IA mouse anti-CEA mAb    Sandwich IA mouse anti-CEA mAb 
 Traceability  First international preparation 73/601  NA  First international preparation 73/601    Internal standards 
 Measuring range  0.5-1,500  0.7-850 Mayo
0.1-1,000 Atrium 
0.5-400    0.5-100 
 Reference interval  <5.0  <5.0  0.5-5.0    <5.0 
Cholesterol, mg/dL           
 Method  Enzymatic  Enzymatic  Enzymatic  Enzymatic  Enzymatic 
 Traceability  Total cholesterol verification set  NIST SRM 1951 b  NIST SRM 911  IDMS  NIST SRM 911 
 Measuring range  7-705  25-700  50-325  10-750  50-600 
 Reference interval  NCEP and the National Lipid Association         
Creatinine, mg/dL           
 Method  Enzymatic  Kinetic alkaline picrate (Jaffe reaction)  Enzymatic  Enzymatic  Enzymatic 
 Traceability  NIST SRM 914  NIST SRM 967a/IDMS  IDMS  IDMS  NIST SRM 914/IDMS 
 Measuring range  0.1-40  0.2-25.0  0.15-14.0  0.1-23.0  0.1-20.0 
 Reference interval (male)  0.7-1.2   0.7-1.3  0.70-1.30a  0.74-1.35a  0.67-1.17 
Glucose, mg/dL           
 Method  Hexokinase G6PDH/UV  Hexokinase G6PDH/UV  Oxidase, colorimetric  Hexokinase G6PDH/UV  Hexokinase G6PDH/UV 
 Traceability  NIST SRM 965  NIST SRM 965b  NIST SRM 917  IDMS  NIST SRM 917 
 Measuring range  5-800  10-800  20-625  2-675  1-500 
 Reference interval  American Diabetes Association Guidelines         
LDH, U/L           
 Method  Lactate → pyruvate  Lactate → pyruvate  Pyruvate → lactate  Lactate → pyruvate  Lactate → pyruvate 
 Traceability  IFCC  Molar absorptivity of NADH  NA  IFCC  IFCC 
 Measuring range  10-3,333  25-1,200  100-2,150  10-900  6-1,000 
 Reference interval  125-220  140-271  338-610  F: 135-214
M: 135-225 
F: 84-246
M: 87-241 
Lipase, U/L           
 Method  Enzymatic colorimetric substrate 1,2 diglyceride, quinone dye  Enzymatic colorimetric substrate 1,2 diglyceride, quinone dye  Enzymatic colorimetric substrate 1-oleoyl-2,3-diacetylglycerol  Enzymatic colorimetric substrate 1,2 diglyceride, quinine dye (Sekisui Diagnostics)  Enzymatic colorimetric substrate DGGR, methylresorufin dye 
 Traceability  NA  NA  NA  NA  NA 
 Measuring range  4-1,200    10-2,000  10-750  10-1,500 
 Reference interval  8-78  11-82  44-232 a  13-60a  73-393 
Total protein, g/dL           
 Method  Biuret  Biuret  Biuret  Biuret  Biuret 
 Traceability  NIST SRM 927  NIST SRM 927d  NIST SRM 927  NIST SRM 927  NIST SRM 927 
 Measuring range  0.8-18.4  3.0-12.0  2.0-11.0  0.5-12.0  0.1-12.0 
 Reference interval  6.4-8.3  6.4-8.9  6.5-8.3a  6.6-8.7  6.4-8.2 
Triglycerides, mg/dL           
 Method  Enzymatic glycerol phosphate oxidase without blank  Enzymatic glycerol phosphate oxidase without blank  Enzymatic colorimetric without blank  Enzymatic glycerol phosphate oxidase without blank  Enzymatic glycerol phosphate oxidase without blank 
 Traceability  ACS grade glycerol  NIST SRM 1951b  NIST SRM1951  IDMS  ACS grade glycerol 
 Measuring range  7-1,420  10-1,000  10-525  10-775  2-1,000 
 Reference interval  NCEP and the National Lipid Association         
Urea nitrogen, mg/dL           
 Method  Urease with glutamate dehydrogenase coupled enzymes  Urease with glutamate dehydrogenase coupled enzymes  Urease quinolinium dye  Urease with glutamate dehydrogenase coupled enzymes  Urease with glutamate dehydrogenase coupled enzymes 
 Traceability  NIST SRM 912  NIST SRM 909b  NIST SRM 912  NIST SRM 912  NIST SRM 912 
 Measuring range  2-125  2-130  2-120  2-100  1-150 
 Reference interval  F: 7.0-18.7
M: 8.9-20.6 
7-25  7-21a  6-20  7-18 

ACS, American Chemical Society; CEA, carcinoembryonic antigen; CNPG3, 2-chloro-4-nitrophenyl-α-D-maltotrioside; CRM, certified reference material; DGGR, 1,2-o-dilauryl-rac-glycero-glutaric acid-(6′-methylresorufin) ester; ERM, European reference material; ethylidene-G7PNP, 4,6-ethylidene-(G7) p-nitrophenyl-(G1)-α-D-maltoheptaoside; G6PDH/UV, glucose-6-phosphate dehydrogenase/ultraviolet; IA, immunoassay; IDMS, isotope dilution mass spectrometry; IFCC, International Federation of Clinical Chemistry; mAb, monoclonal antibody; NA, not available; NCEP, National Cholesterol Education Program; NIST, National Institute of Standards and Technology; SRM, Standard Reference Material.

a Internal study/established.


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Overall, there were no statistical differences between the five instruments measuring chemistry analytes (eg, P > .05) except for lipase and LDH Table 2. No distinct bias was observed between serum and BFs or different BF types when measuring albumin, total protein, amylase, LDH, lipase, bilirubin, and triglyceride. Further instrument- and method-specific details are provided for each analyte.

Table 2

Results From Analysis of Method Comparison Data

Characteristic No. Slope (95% CI) y-intercept (95% CI) r Mean Bias (%) P ICC
Albumin               
 Abbott  30  1.00 (0.93 to 1.08)  0.03 (–0.14 to 0.20)  0.98  0.04 (1.9)  1.0  0.98 
 Beckman  21  0.94 (0.82 to 1.05)  0.13 (–0.17 to 0.43)  0.97  –0.02 (–0.8)  .9  0.97 
 Ortho  23  1.12 (0.86 to 1.39)  –0.4 (–1.1 to 0.2)  0.87  –0.13 (–5.6)  1.0  0.86 
 Siemens  30  0.89 (0.83 to 0.94)  0.02 (–0.11 to 0.14)  0.99  –0.21 (–10.7)  1.0  0.96 
Total protein               
 Abbott  29  1.07 (1.02 to 1.12)  –0.3 (–0.5 to –0.1)  0.99  –0.06 (–1.5)  1.0  0.99 
 Beckman  21  0.99 (0.95 to 1.03)  0.02 (–0.2 to 0.2)  1.00  –0.03 (–0.6)  1.0  1.00 
 Ortho  23  1.01 (0.96 to 1.06)  –0.3 (–0.6 to 0.1)  0.99  –0.26 (–5.7)  1.0  0.98 
 Siemens  30  1.05 (1.03 to 1.07)  –0.1 (–0.2 to 0.01)  1.00  0.10 (2.6)  1.0  1.00 
Amylase               
 Abbott  28  0.95 (0.94 to 0.97)  –2.1 (–6.9 to 2.7)  1.00  –10.3 (–6.2)  1.0  1.00 
 Beckman  26  0.76 (0.74 to 0.77)  –0.9 (–4.9 to 3.1)  1.00  –46.0 (–24.9)  1.0  0.95 
 Ortho  13  1.02 (0.96 to 1.08)  3.8 (–25.8 to 33.4)  1.00  10.9 (3.2)  .4  1.00 
 Siemens  28  0.99 (0.96 to 1.01)  –3.8 (–12.2 to 4.6)  1.00  –6.0 (–3.5)  1.0  1.00 
LDH               
 Abbott  21  1.11 (1.06 to 1.16)  –17.2 (–32.8 to –1.7)  1.00  8.7 (3.6)  1.0  0.99 
 Beckman  21  0.94 (0.88 to 0.99)  –19.2 (–35.7 to –2.7)  0.99  –35.0 (–14.5)  1.0  0.98 
 Ortho  21  2.75 (2.54 to 2.96)  –42 (–108 to 24)  0.99  380 (157)  <.01a  0.39 
 Siemens  21  0.98 (0.97 to 1.00)  –0.8 (–4.8 to 3.3)  1.00  –4.7 (–2.0)  1.0  1.00 
Lipase               
 Abbott  30  0.96 (0.95 to 0.97)  2.2 (–1.2 to 5.5)  1.00  –8.2 (–3.4)  1.0  1.00 
 Beckman  30  0.98 (0.96 to 1.00)  –2.2 (–10.7 to 6.3)  1.00  –7.1 (–2.9)  1.0  1.00 
 Ortho  30  3.42 (3.11 to 3.73)  20 (–95 to 135)  0.97  601 (250)  <.01 a  0.31 
 Siemens  29  3.14 (2.81 to 3.47)  32 (–93 to 157)  0.96  563 (227)  <.01 a  0.33 
Bilirubin               
 Abbott  30  1.03 (1.02 to 1.04)  0.1 (–0.1 to 0.2)  1.00  0.3 (3.4)  1.0  1.00 
 Beckman  30  1.02 (1.01 to 1.04)  –0.2 (–0.4 to 0.1)  1.00  0.06 (0.7)  1.0  1.00 
 Ortho  30  0.96 (0.94 to 0.98)  0.4 (0.1 to 0.7)  1.00  –0.05 (–0.5)  1.0  1.00 
 Siemens  30  1.00 (0.98 to 1.02)  0.1 (–0.2 to 0.4)  1.00  0.09 (0.9)  1.0  1.00 
Cholesterol               
 Abbott  30  1.03 (1.00 to 1.06)  –1.8 (–5.7 to 2.1)  1.00  0.6 (0.7)  1.0  1.00 
 Beckman  26  1.02 (1.00 to 1.05)  –6.0 (–9.3 to –2.8)  1.00  –3.9 (–4.0)  1.0  1.00 
 Ortho  12  0.97 (0.93 to 1.01)  –2.9 (–10.4 to 4.7)  1.00  –7.8 (–4.9)  .7  1.00 
 Siemens  15  0.92 (0.86 to 0.97)  4.8 (–4.8 to 14.5)  1.00  –6.7 (–4.8)  1.0  1.00 
Creatinine               
 Abbott  30  1.04 (1.02 to 1.05)  –0.1 (–0.2 to 0.0)  1.00  0.05 (1.1)  1.0  1.00 
 Beckman  29  1.01 (0.99 to 1.02)  –0.1 (–0.2 to 0.0)  1.00  –0.0 (–0.8)  1.0  1.00 
 Ortho  30  0.97 (0.95 to 0.98)  –0.1 (–0.2 to 0.0)  1.00  –0.2 (–4.8)  1.0  1.00 
 Siemens  30  1.03 (1.02 to 1.04)  –0.1 (–0.1 to 0.0)  1.00  0.1 (1.3)  1.0  1.00 
Glucose               
 Abbott  30  1.04 (1.02 to 1.05)  –5.1 (–8.5 to –1.7)  1.00  1.2 (0.8)  1.0  1.00 
 Beckman  28  1.03 (1.02 to 1.04)  –2.3 (–4.9 to 0.3)  1.00  2.2 (1.3)  1.0  1.00 
 Ortho  27  0.89 (0.86 to 0.92)  4.1 (–3.0 to 11.2)  1.00  –15.4 (–8.7)  1.0  0.99 
 Siemens  30  0.96 (0.94 to 0.99)  –1.5 (–6.3 to 3.4)  1.00  –7.2 (–4.5)  1.0  1.00 
Triglycerides               
 Abbott  30  0.95 (0.89 to 1.00)  6.8 (–3.1 to 16.7)  0.99  1.6 (1.7)  1.0  0.99 
 Beckman  30  1.02 (0.99 to 1.04)  –3.1 (–7.3 to 1.1)  1.00  –1.4 (–1.5)  1.0  1.00 
 Ortho  30  0.94 (0.88 to 1.00)  1.5 (–9.1 to 12.0)  0.99  –4.3 (–4.6)  1.0  0.98 
 Siemens  30  0.93 (0.90 to 0.96)  6.9 (2.1 to 11.8)  1.00  0.5 (0.5)  1.0  1.00 
Urea nitrogen               
 Abbott  30  1.02 (1.00 to 1.03)  0.3 (–0.4 to 1.0)  1.00  0.9 (2.7)  1.0  1.00 
 Beckman  30  1.00 (0.98 to 1.03)  0.9 (–0.1 to 1.9)  1.00  0.9 (2.9)  1.0  1.00 
 Ortho  30  0.92 (0.88 to 0.96)  0.7 (–1.1 to 2.5)  0.99  –1.8 (–5.8)  1.0  1.00 
 Siemens  30  1.00 (0.98 to 1.02)  0.5 (–0.4 to 1.3)  1.00  0.5 (1.6)  1.0  1.00 
CEA               
 Abbott  29  0.99 (0.87 to 1.12)  7.9 (–25.6 to 41.4)  0.95  7.0 (5.7)  1.0  0.95 
 Beckman  30  0.97 (0.95 to 0.98)  0.0 (–3.6 to 3.6)  1.00  –4.2 (–3.5)  1.0  1.00 
 Ortho  30  0.94 (0.82 to 1.05)  2.7 (–27.7 to 33.1)  0.95  –5.1 (–4.3)  1.0  0.95 
 Siemens  26  0.72 (0.67 to 0.78)  0.3 (–15.3 to 15.9)  0.98  –38.2 (–27.5)  1.0  0.92 
Characteristic No. Slope (95% CI) y-intercept (95% CI) r Mean Bias (%) P ICC
Albumin               
 Abbott  30  1.00 (0.93 to 1.08)  0.03 (–0.14 to 0.20)  0.98  0.04 (1.9)  1.0  0.98 
 Beckman  21  0.94 (0.82 to 1.05)  0.13 (–0.17 to 0.43)  0.97  –0.02 (–0.8)  .9  0.97 
 Ortho  23  1.12 (0.86 to 1.39)  –0.4 (–1.1 to 0.2)  0.87  –0.13 (–5.6)  1.0  0.86 
 Siemens  30  0.89 (0.83 to 0.94)  0.02 (–0.11 to 0.14)  0.99  –0.21 (–10.7)  1.0  0.96 
Total protein               
 Abbott  29  1.07 (1.02 to 1.12)  –0.3 (–0.5 to –0.1)  0.99  –0.06 (–1.5)  1.0  0.99 
 Beckman  21  0.99 (0.95 to 1.03)  0.02 (–0.2 to 0.2)  1.00  –0.03 (–0.6)  1.0  1.00 
 Ortho  23  1.01 (0.96 to 1.06)  –0.3 (–0.6 to 0.1)  0.99  –0.26 (–5.7)  1.0  0.98 
 Siemens  30  1.05 (1.03 to 1.07)  –0.1 (–0.2 to 0.01)  1.00  0.10 (2.6)  1.0  1.00 
Amylase               
 Abbott  28  0.95 (0.94 to 0.97)  –2.1 (–6.9 to 2.7)  1.00  –10.3 (–6.2)  1.0  1.00 
 Beckman  26  0.76 (0.74 to 0.77)  –0.9 (–4.9 to 3.1)  1.00  –46.0 (–24.9)  1.0  0.95 
 Ortho  13  1.02 (0.96 to 1.08)  3.8 (–25.8 to 33.4)  1.00  10.9 (3.2)  .4  1.00 
 Siemens  28  0.99 (0.96 to 1.01)  –3.8 (–12.2 to 4.6)  1.00  –6.0 (–3.5)  1.0  1.00 
LDH               
 Abbott  21  1.11 (1.06 to 1.16)  –17.2 (–32.8 to –1.7)  1.00  8.7 (3.6)  1.0  0.99 
 Beckman  21  0.94 (0.88 to 0.99)  –19.2 (–35.7 to –2.7)  0.99  –35.0 (–14.5)  1.0  0.98 
 Ortho  21  2.75 (2.54 to 2.96)  –42 (–108 to 24)  0.99  380 (157)  <.01a  0.39 
 Siemens  21  0.98 (0.97 to 1.00)  –0.8 (–4.8 to 3.3)  1.00  –4.7 (–2.0)  1.0  1.00 
Lipase               
 Abbott  30  0.96 (0.95 to 0.97)  2.2 (–1.2 to 5.5)  1.00  –8.2 (–3.4)  1.0  1.00 
 Beckman  30  0.98 (0.96 to 1.00)  –2.2 (–10.7 to 6.3)  1.00  –7.1 (–2.9)  1.0  1.00 
 Ortho  30  3.42 (3.11 to 3.73)  20 (–95 to 135)  0.97  601 (250)  <.01 a  0.31 
 Siemens  29  3.14 (2.81 to 3.47)  32 (–93 to 157)  0.96  563 (227)  <.01 a  0.33 
Bilirubin               
 Abbott  30  1.03 (1.02 to 1.04)  0.1 (–0.1 to 0.2)  1.00  0.3 (3.4)  1.0  1.00 
 Beckman  30  1.02 (1.01 to 1.04)  –0.2 (–0.4 to 0.1)  1.00  0.06 (0.7)  1.0  1.00 
 Ortho  30  0.96 (0.94 to 0.98)  0.4 (0.1 to 0.7)  1.00  –0.05 (–0.5)  1.0  1.00 
 Siemens  30  1.00 (0.98 to 1.02)  0.1 (–0.2 to 0.4)  1.00  0.09 (0.9)  1.0  1.00 
Cholesterol               
 Abbott  30  1.03 (1.00 to 1.06)  –1.8 (–5.7 to 2.1)  1.00  0.6 (0.7)  1.0  1.00 
 Beckman  26  1.02 (1.00 to 1.05)  –6.0 (–9.3 to –2.8)  1.00  –3.9 (–4.0)  1.0  1.00 
 Ortho  12  0.97 (0.93 to 1.01)  –2.9 (–10.4 to 4.7)  1.00  –7.8 (–4.9)  .7  1.00 
 Siemens  15  0.92 (0.86 to 0.97)  4.8 (–4.8 to 14.5)  1.00  –6.7 (–4.8)  1.0  1.00 
Creatinine               
 Abbott  30  1.04 (1.02 to 1.05)  –0.1 (–0.2 to 0.0)  1.00  0.05 (1.1)  1.0  1.00 
 Beckman  29  1.01 (0.99 to 1.02)  –0.1 (–0.2 to 0.0)  1.00  –0.0 (–0.8)  1.0  1.00 
 Ortho  30  0.97 (0.95 to 0.98)  –0.1 (–0.2 to 0.0)  1.00  –0.2 (–4.8)  1.0  1.00 
 Siemens  30  1.03 (1.02 to 1.04)  –0.1 (–0.1 to 0.0)  1.00  0.1 (1.3)  1.0  1.00 
Glucose               
 Abbott  30  1.04 (1.02 to 1.05)  –5.1 (–8.5 to –1.7)  1.00  1.2 (0.8)  1.0  1.00 
 Beckman  28  1.03 (1.02 to 1.04)  –2.3 (–4.9 to 0.3)  1.00  2.2 (1.3)  1.0  1.00 
 Ortho  27  0.89 (0.86 to 0.92)  4.1 (–3.0 to 11.2)  1.00  –15.4 (–8.7)  1.0  0.99 
 Siemens  30  0.96 (0.94 to 0.99)  –1.5 (–6.3 to 3.4)  1.00  –7.2 (–4.5)  1.0  1.00 
Triglycerides               
 Abbott  30  0.95 (0.89 to 1.00)  6.8 (–3.1 to 16.7)  0.99  1.6 (1.7)  1.0  0.99 
 Beckman  30  1.02 (0.99 to 1.04)  –3.1 (–7.3 to 1.1)  1.00  –1.4 (–1.5)  1.0  1.00 
 Ortho  30  0.94 (0.88 to 1.00)  1.5 (–9.1 to 12.0)  0.99  –4.3 (–4.6)  1.0  0.98 
 Siemens  30  0.93 (0.90 to 0.96)  6.9 (2.1 to 11.8)  1.00  0.5 (0.5)  1.0  1.00 
Urea nitrogen               
 Abbott  30  1.02 (1.00 to 1.03)  0.3 (–0.4 to 1.0)  1.00  0.9 (2.7)  1.0  1.00 
 Beckman  30  1.00 (0.98 to 1.03)  0.9 (–0.1 to 1.9)  1.00  0.9 (2.9)  1.0  1.00 
 Ortho  30  0.92 (0.88 to 0.96)  0.7 (–1.1 to 2.5)  0.99  –1.8 (–5.8)  1.0  1.00 
 Siemens  30  1.00 (0.98 to 1.02)  0.5 (–0.4 to 1.3)  1.00  0.5 (1.6)  1.0  1.00 
CEA               
 Abbott  29  0.99 (0.87 to 1.12)  7.9 (–25.6 to 41.4)  0.95  7.0 (5.7)  1.0  0.95 
 Beckman  30  0.97 (0.95 to 0.98)  0.0 (–3.6 to 3.6)  1.00  –4.2 (–3.5)  1.0  1.00 
 Ortho  30  0.94 (0.82 to 1.05)  2.7 (–27.7 to 33.1)  0.95  –5.1 (–4.3)  1.0  0.95 
 Siemens  26  0.72 (0.67 to 0.78)  0.3 (–15.3 to 15.9)  0.98  –38.2 (–27.5)  1.0  0.92 

CEA, carcinoembryonic antigen; CI, confidence interval; ICC, intraclass correlation coefficient; LDH, lactate dehydrogenase.

a Statistically significant.


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Preanalytical Specimen Handling

RESULTS

Analytical Methods and Calibration Traceability

LDH measurement revealed there was a statistical difference between the five instruments (P < .05). The pairwise comparison and ICC demonstrated Ortho was the outlier Table 2. Figure 1D demonstrates the largest bias (157%) between Roche and Ortho methods, followed by Roche and Beckman (–15%).

Lipase measurement also revealed there was a statistical difference between the five instruments (P < .05). The pairwise comparison and ICC demonstrated significant differences between Roche and both Ortho and Siemens. The pairwise comparison of Ortho to Siemens did not reveal a significant difference, suggesting they produce comparable results. Figure 1E demonstrates Abbott and Beckman methods produced results with the smallest bias (–3.5% and –3.0%, respectively) compared with Roche while the Ortho and Siemens methods had the greatest bias (250% and 227%, respectively).

Figure 2A demonstrates minimal bias with all methods with differences less than +1 mg/dL or 10%. The largest bias overall (0.3 mg/dL or 3%) was between Abbott and Roche.

Bias calculated between Roche and all platforms was within ±5% Table 2. Figure 2B demonstrates most negative bias occurred at low concentrations less than 100 mg/dL.

Overall, the greatest overall bias (–5%) was observed between Roche and Ortho Table 2. Figure 2C demonstrates BFs with a concentration more than 3 mg/dL had a greater mean absolute (SD) and percent difference (SD) (–0.5 [0.3] mg/dL or –6.6% [4.0%]) using Ortho compared with serum (<0.01 [0.1] mg/dL or –0.6% [2.6%]). Peritoneal dialysis fluid (n = 3) had the largest mean (SD) difference (–0.7 [0.3] mg/dL) and percent difference (–8.2% [1.0%]), a trend also observed in drain and peritoneal fluids. The absolute differences remained within ±0.1 mg/dL at concentrations less than 2 mg/dL for all methods. The other methods did not demonstrate such BF to serum bias compared with Roche Figure 2C and Table 3.

The largest overall bias was observed between Roche and Ortho methods (–8.7%) Table 2. Figure 2D demonstrates there were differences observed between BFs and serum for Ortho and Siemens. The peritoneal fluid tested by Ortho had the largest mean (SD) percent difference at –13.5% (2.1%) (n = 5) relative to serum (–1.6% [2.7%], n = 5). The BFs tested by Siemens had a mean –6.7% difference (n = 19 with concentration >50 mg/dL) compared with serum (4.6%, n = 5) with no obvious specimen type differences Table 3.

The greatest amount of overall bias was observed between Ortho and Roche (–4.6%) while all other methods had a bias less than +2% Table 2. Figure 2E demonstrates the absolute differences are less than ±10 mg/dL or ±20% for 90% of samples tested by Ortho, 93% by Abbott and Beckman, and 100% by Siemens.

Data Analysis

The regression analysis demonstrated the greatest amount of bias between Ortho and Roche at –6%, and all other methods had bias within 3% Table 2. The absolute differences were less than ±1.6 mg/dL at concentrations less than 24 mg/dL, with Ortho’s proportional bias (slope = 0.92) giving rise to larger negative percent differences at concentrations more than 30 mg/dL Figure 2F, demonstrating mean difference (SD) and percent difference (SD) of –6.4 (3.2) mg/dL and –9.9% (3.8%), with peritoneal and peritoneal dialysis fluid contributing most significantly to the observed bias Table 3. There was an observed trend for all methods in which serum appeared to have the most positive bias compared with Roche, with no BF-specific trends Table 3.

Albumin

Figure 2G demonstrates the poorest agreement between Siemens and Beckman instruments with slope = 0.72 and bias = –32% Table 2. The best agreement was with Beckman, as expected, when comparing two similar instruments. Overall agreement between all non-Siemens methods demonstrated bias within +5%. The absolute differences below 10 ng/mL were less than ±5 ng/mL, but there were slightly lower correlations (ICCs ranged from 0.92 to 0.95) and percent differences ranging from 50% to –100%.

Figure 2
 Bland-Altman plot showing absolute difference and percent difference for bilirubin (A), cholesterol (B), creatinine (C), glucose (D), triglycerides (E), and urea nitrogen (F). Bland-Altman plot showing carcinoembryonic antigen (CEA) (G, H). The following colors apply to Ortho (black), Abbott (red), Siemens (blue), and Beckman (green). The following symbols apply to peritoneal fluid (■), pleural fluid (●), drain fluid (▲), pericardial fluid (►), peritoneal dialysate fluid (◄), synovial fluid (⋆), amniotic fluid (✚), and serum (▼).

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 Bland-Altman plot showing absolute difference and percent difference for bilirubin (A), cholesterol (B), creatinine (C), glucose (D), triglycerides (E), and urea nitrogen (F). Bland-Altman plot showing carcinoembryonic antigen (CEA) (G, H). The following colors apply to Ortho (black), Abbott (red), Siemens (blue), and Beckman (green). The following symbols apply to peritoneal fluid (■), pleural fluid (●), drain fluid (▲), pericardial fluid (►), peritoneal dialysate fluid (◄), synovial fluid (⋆), amniotic fluid (✚), and serum (▼).

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Bland-Altman plot showing absolute difference and percent difference for bilirubin (A), cholesterol (B), creatinine (C), glucose (D), triglycerides (E), and urea nitrogen (F). Bland-Altman plot showing carcinoembryonic antigen (CEA) (G, H). The following colors apply to Ortho (black), Abbott (red), Siemens (blue), and Beckman (green). The following symbols apply to peritoneal fluid (■), pleural fluid (●), drain fluid (▲), pericardial fluid (►), peritoneal dialysate fluid (◄), synovial fluid (⋆), amniotic fluid (✚), and serum (▼).

Bland-Altman plot showing absolute difference for albumin (A) and total protein (B) and percent difference for amylase (C), lactate dehydrogenase (LDH) (D), and lipase (E). The following colors apply to Ortho (black), Abbott (red), Siemens (blue), and Beckman (green). The following symbols apply to peritoneal fluid (■), pleural fluid (●), drain fluid (▲), pericardial fluid (►), synovial fluid (⋆), and serum (▼).

 Bland-Altman plot showing absolute difference and percent difference for bilirubin (A), cholesterol (B), creatinine (C), glucose (D), triglycerides (E), and urea nitrogen (F). Bland-Altman plot showing carcinoembryonic antigen (CEA) (G, H). The following colors apply to Ortho (black), Abbott (red), Siemens (blue), and Beckman (green). The following symbols apply to peritoneal fluid (■), pleural fluid (●), drain fluid (▲), pericardial fluid (►), peritoneal dialysate fluid (◄), synovial fluid (⋆), amniotic fluid (✚), and serum (▼).

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The primary utility in comparing results of BF testing across multiple instruments is to first put the magnitude of bias in perspective of other studies, identify whether it is BF specific, and relate these findings to how BF results are interpreted. This information is valuable to laboratories to gauge the transferability of literature findings from one method to another in the provision of interpretive guidance. These comparisons are also useful when replacing instruments in the laboratory, particularly when the vendor changes. The following is a systematic evaluation of each analyte as it relates to the significance of the differences observed from this study.

Table 3

Analysis of Differences Between Specimen Types for Creatinine, Glucose, and Urea Nitrogen

Analyte Sample Type/Method No. Mean Difference (SD) Mean % Difference (SD)
Creatinine >3 mg/dL  Drain     
   Ortho    –0.5 (0.3)  –8.7 (9.9) 
   Abbott    0.2 (0.4)  1.0 (3.0) 
   Siemens    0.1 (0.4)  –0.4 (4.1) 
   Beckman    0.1 (0.4)  –1.0 (4.9) 
  Peritoneal     
   Ortho    –0.5 (0.2)  –4.8 (1.5) 
   Abbott    0.1 (0.6)  –0.1 (4.3) 
   Siemens    0.1 (0.3)  1.1 (1.7) 
   Beckman    –0.1 (0.4)  –0.9 (2.5) 
  Peritoneal dialysate fluid     
   Ortho    –0.7 (0.3)  –8.2 (1.0) 
   Abbott    0.2 (0.5)  1.5 (4.8) 
   Siemens    0.2 (0.4)  2.0 (3.5) 
   Beckman    0.0 (0.2)  –0.3 (2.5) 
  Pleural  NA  NA 
  Serum     
   Ortho    0.0 (0.1)  –0.6 (2.6) 
   Abbott    0.2 (0.2)  3.0 (2.5) 
   Siemens    0.1 (0.2)  1.0 (3.1) 
   Beckman    0.1 (0.1)  1.9 (1.6) 
  All body fluids  10     
   Ortho  10  –0.5 (0.3)  –6.6 (4.0) 
   Abbott    0.2 (0.5)  0.6 (3.9) 
   Siemens    0.2 (0.3)  1.1 (2.6) 
   Beckman    0.0 (0.3)  –0.8 (2.6) 
Creatinine <3 mg/dL   Drain       
   Ortho  –0.1 (0.0)   
   Abbott  0.0 (0.0)   
   Siemens  0.0 (0.0)   
   Beckman  –0.1 (0.0)   
  Peritoneal     
   Ortho    0.0 (0.1)   
   Abbott    –0.1 (0.0)   
   Siemens    0.0 (0.1)   
   Beckman    –0.1 (0.1)   
  Peritoneal dialysate fluid  NA  NA 
  Pleural     
   Ortho    –0.1 (0.1)   
   Abbott    –0.1 (0.1)   
   Siemens    0.0 (0.0)   
   Beckman    0.0 (0.0)   
  Serum       
   Ortho    –0.1 (0.0)   
   Abbott    –0.1 (0.0)   
   Siemens    –0.1 (0.0)   
   Beckman    –0.1 (0.1)   
  All body fluids       
   Ortho  15  –0.1 (0.1)   
   Abbott  15  –0.1 (0.1)   
   Siemens  15  0.0 (0.0)   
   Beckman  14  –0.1 (0.0)   
Glucose   Amniotic     
   Ortho      –10.8 (2.4) 
   Abbott      –4.8 (2.0) 
   Siemens      –12.4 (4.6) 
   Beckman      2.6 (3.6) 
  Drain       
   Ortho    –7.5 (1.0) 
   Abbott    –3.8 (3.1) 
   Siemens    –11.7 (9.1) 
   Beckman    –0.9 (2.8) 
  Pleural     
   Ortho      –5.9 (4.8) 
   Abbott      –1.9 (2.6) 
   Siemens      –5.4 (2.4) 
   Beckman      0.4 (1.6) 
  Peritoneal dialysate fluid     
   Ortho      –13.8 
   Abbott      –4.5 
   Siemens      –6.2 
   Beckman      3.5 
  Pericardial     
   Ortho      –2.8 (4.8) 
   Abbott      –5.4 (4.1) 
   Siemens      –7.6 (1.0) 
   Beckman      –2.4 (4.1) 
  Peritoneal     
   Ortho      –13.5 (2.1) 
   Abbott      –2.3 (4.2) 
   Siemens      –8.1 (3.6) 
   Beckman      0.4 (3.5) 
  Synovial       
   Ortho    –5.4 (0.8) 
   Abbott    –1.4 (4.0) 
   Siemens    –9.4 (11.7) 
   Beckman    1.0 (2.9) 
  Serum     
   Ortho      –1.6 (2.7) 
   Abbott      4.5 (3.5) 
   Siemens      4.6 (12.4) 
   Beckman      1.2 (2.8) 
  All body fluids       
   Ortho  22    –8.7 (4.3) 
        –2.6 (3.6) 
   Abbott  25    –8.6 (6.4) 
        0.3 (2.8) 
    Siemens  25     
   Beckman  23     
  Body fluids with glucose >50 mg/dL  19     
   Ortho      –8.9 (4.0) 
   Abbott      –2.1 (3.1) 
   Siemens      –6.7 (2.9) 
   Beckman      0.5 (2.6) 
Urea nitrogen   Drain     
   Ortho    –0.2 (1.2)  –0.9 (7.9) 
   Abbott    0.7 (0.5)  6.7 (4.8) 
   Siemens    0.0 (0.8)  0.9 (10.6) 
   Beckman    1.3 (1.4)  8.6 (3.1) 
  Pleural     
   Ortho    –0.8 (1.3)  –1.4 (3.6) 
   Abbott    0.2 (0.3)  1.0 (1.9) 
   Siemens    0.6 (0.4)  5.5 (6.5) 
   Beckman    1.0 (1.1)  4.3 (5.7) 
  Peritoneal dialysis fluid     
   Ortho    –7.3 (4.0)  –14.7 (2.3) 
   Abbott    0.2 (0.4)  0.8 (1.4) 
   Siemens    0.2 (0.4)  0.8 (1.4) 
   Beckman    0.7 (0.3)  1.5 (0.5) 
  Peritoneal     
   Ortho    –5.3 (3.8)  –10.6 (2.9) 
   Abbott    0.6 (0.8)  1.6 (2.4) 
   Siemens    –0.4 (0.9)  0.6 (3.7) 
   Beckman    –0.6 (1.4)  1.3 (5.0) 
  Serum     
   Ortho    2.1 (2.6)  3.5 (8.6) 
   Abbott    2.8 (2.0)  9.4 (2.1) 
   Siemens    2.6 (2.2)  7.8 (3.7) 
   Beckman    2.8 (2.0)  9.3 (3.0) 
  All body fluids  25     
   Ortho    –2.6 (3.6)  –5.3 (7.0) 
   Abbott    0.5 (0.6)  2.8 (3.9) 
   Siemens    0.1 (0.8)  2.3 (7.0) 
   Beckman    0.6 (1.4)  4.3 (5.3) 
  Body fluids with urea nitrogen >30 mg/dL     
   Ortho    –6.4 (3.2)  –9.9 (3.8) 
   Abbott    0.6 (0.8)  1.0 (1.2) 
   Siemens    –0.4 (0.8)  –0.5 (1.2) 
   Beckman    0.2 (2.3)  0.7 (4.2) 
Analyte Sample Type/Method No. Mean Difference (SD) Mean % Difference (SD)
Creatinine >3 mg/dL  Drain     
   Ortho    –0.5 (0.3)  –8.7 (9.9) 
   Abbott    0.2 (0.4)  1.0 (3.0) 
   Siemens    0.1 (0.4)  –0.4 (4.1) 
   Beckman    0.1 (0.4)  –1.0 (4.9) 
  Peritoneal     
   Ortho    –0.5 (0.2)  –4.8 (1.5) 
   Abbott    0.1 (0.6)  –0.1 (4.3) 
   Siemens    0.1 (0.3)  1.1 (1.7) 
   Beckman    –0.1 (0.4)  –0.9 (2.5) 
  Peritoneal dialysate fluid     
   Ortho    –0.7 (0.3)  –8.2 (1.0) 
   Abbott    0.2 (0.5)  1.5 (4.8) 
   Siemens    0.2 (0.4)  2.0 (3.5) 
   Beckman    0.0 (0.2)  –0.3 (2.5) 
  Pleural  NA  NA 
  Serum     
   Ortho    0.0 (0.1)  –0.6 (2.6) 
   Abbott    0.2 (0.2)  3.0 (2.5) 
   Siemens    0.1 (0.2)  1.0 (3.1) 
   Beckman    0.1 (0.1)  1.9 (1.6) 
  All body fluids  10     
   Ortho  10  –0.5 (0.3)  –6.6 (4.0) 
   Abbott    0.2 (0.5)  0.6 (3.9) 
   Siemens    0.2 (0.3)  1.1 (2.6) 
   Beckman    0.0 (0.3)  –0.8 (2.6) 
Creatinine <3 mg/dL   Drain       
   Ortho  –0.1 (0.0)   
   Abbott  0.0 (0.0)   
   Siemens  0.0 (0.0)   
   Beckman  –0.1 (0.0)   
  Peritoneal     
   Ortho    0.0 (0.1)   
   Abbott    –0.1 (0.0)   
   Siemens    0.0 (0.1)   
   Beckman    –0.1 (0.1)   
  Peritoneal dialysate fluid  NA  NA 
  Pleural     
   Ortho    –0.1 (0.1)   
   Abbott    –0.1 (0.1)   
   Siemens    0.0 (0.0)   
   Beckman    0.0 (0.0)   
  Serum       
   Ortho    –0.1 (0.0)   
   Abbott    –0.1 (0.0)   
   Siemens    –0.1 (0.0)   
   Beckman    –0.1 (0.1)   
  All body fluids       
   Ortho  15  –0.1 (0.1)   
   Abbott  15  –0.1 (0.1)   
   Siemens  15  0.0 (0.0)   
   Beckman  14  –0.1 (0.0)   
Glucose   Amniotic     
   Ortho      –10.8 (2.4) 
   Abbott      –4.8 (2.0) 
   Siemens      –12.4 (4.6) 
   Beckman      2.6 (3.6) 
  Drain       
   Ortho    –7.5 (1.0) 
   Abbott    –3.8 (3.1) 
   Siemens    –11.7 (9.1) 
   Beckman    –0.9 (2.8) 
  Pleural     
   Ortho      –5.9 (4.8) 
   Abbott      –1.9 (2.6) 
   Siemens      –5.4 (2.4) 
   Beckman      0.4 (1.6) 
  Peritoneal dialysate fluid     
   Ortho      –13.8 
   Abbott      –4.5 
   Siemens      –6.2 
   Beckman      3.5 
  Pericardial     
   Ortho      –2.8 (4.8) 
   Abbott      –5.4 (4.1) 
   Siemens      –7.6 (1.0) 
   Beckman      –2.4 (4.1) 
  Peritoneal     
   Ortho      –13.5 (2.1) 
   Abbott      –2.3 (4.2) 
   Siemens      –8.1 (3.6) 
   Beckman      0.4 (3.5) 
  Synovial       
   Ortho    –5.4 (0.8) 
   Abbott    –1.4 (4.0) 
   Siemens    –9.4 (11.7) 
   Beckman    1.0 (2.9) 
  Serum     
   Ortho      –1.6 (2.7) 
   Abbott      4.5 (3.5) 
   Siemens      4.6 (12.4) 
   Beckman      1.2 (2.8) 
  All body fluids       
   Ortho  22    –8.7 (4.3) 
        –2.6 (3.6) 
   Abbott  25    –8.6 (6.4) 
        0.3 (2.8) 
    Siemens  25     
   Beckman  23     
  Body fluids with glucose >50 mg/dL  19     
   Ortho      –8.9 (4.0) 
   Abbott      –2.1 (3.1) 
   Siemens      –6.7 (2.9) 
   Beckman      0.5 (2.6) 
Urea nitrogen   Drain     
   Ortho    –0.2 (1.2)  –0.9 (7.9) 
   Abbott    0.7 (0.5)  6.7 (4.8) 
   Siemens    0.0 (0.8)  0.9 (10.6) 
   Beckman    1.3 (1.4)  8.6 (3.1) 
  Pleural     
   Ortho    –0.8 (1.3)  –1.4 (3.6) 
   Abbott    0.2 (0.3)  1.0 (1.9) 
   Siemens    0.6 (0.4)  5.5 (6.5) 
   Beckman    1.0 (1.1)  4.3 (5.7) 
  Peritoneal dialysis fluid     
   Ortho    –7.3 (4.0)  –14.7 (2.3) 
   Abbott    0.2 (0.4)  0.8 (1.4) 
   Siemens    0.2 (0.4)  0.8 (1.4) 
   Beckman    0.7 (0.3)  1.5 (0.5) 
  Peritoneal     
   Ortho    –5.3 (3.8)  –10.6 (2.9) 
   Abbott    0.6 (0.8)  1.6 (2.4) 
   Siemens    –0.4 (0.9)  0.6 (3.7) 
   Beckman    –0.6 (1.4)  1.3 (5.0) 
  Serum     
   Ortho    2.1 (2.6)  3.5 (8.6) 
   Abbott    2.8 (2.0)  9.4 (2.1) 
   Siemens    2.6 (2.2)  7.8 (3.7) 
   Beckman    2.8 (2.0)  9.3 (3.0) 
  All body fluids  25     
   Ortho    –2.6 (3.6)  –5.3 (7.0) 
   Abbott    0.5 (0.6)  2.8 (3.9) 
   Siemens    0.1 (0.8)  2.3 (7.0) 
   Beckman    0.6 (1.4)  4.3 (5.3) 
  Body fluids with urea nitrogen >30 mg/dL     
   Ortho    –6.4 (3.2)  –9.9 (3.8) 
   Abbott    0.6 (0.8)  1.0 (1.2) 
   Siemens    –0.4 (0.8)  –0.5 (1.2) 
   Beckman    0.2 (2.3)  0.7 (4.2) 

NA, not available.


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For albumin, the magnitude of bias observed between methods in this study is comparable to the bias reported between methods in serum and plasma pools using several instruments with bromocresol green (BCG) and bromocresol purple (BCP) assays compared with a reference nephelometric method.3 They noted greater bias and a larger difference in albumin between serum and plasma using the BCG assays, leading to the conclusion that laboratories should standardize to the BCP methods. One laboratory using an Abbott instrument reported its conversion experience. It demonstrated the expected –0.35 g/dL difference in serum samples but not peritoneal fluid samples (–0.03 g/dL).4 The comparison presented herein did not appear to demonstrate a disproportionate bias in serum compared with BFs but rather a difference that depended on albumin concentration. Ultimately serum-ascites albumin gradient (SAAG) (the difference between serum albumin and ascites albumin used to differentiate causes of ascites) was reclassified in 4 of the 22 paired samples using the BCP reagent, suggesting further investigation is warranted.4 In conclusion for albumin, while the differences were small, there could be issues with interpreting SAAG values if there is a disproportionate bias in serum and BF matrix that we did not specifically test in this study. Laboratories should be mindful of how well the SAAG decision limit of more than 1.1 g/dL applies to their patient population to properly classify the presence or absence of portal hypertension.5

Discussion

Total Protein

For amylase, the magnitude of bias observed between methods in this study is comparable to the bias reported in commutable trueness verification pools9 and is commensurate with the observed differences in reference intervals Table 1. These differences have been attributed to the variation in substrates and reaction conditions that is known to contribute to nonharmonized enzyme results. The interpretation of BF amylase involves comparing the concentration in a BF to either the measurement of amylase in serum collected near the time the BF is collected or the comparison of BF amylase to the expected concentration for serum, such as the upper limit of normal for the assay, in which a several-fold elevation above serum suggests the presence of pancreatic fluid.7,10 In conclusion for amylase, while there is a notable bias observed between methods, it is similar in magnitude between BF and serum, thereby negating the risk for misinterpreting results using a given assay. In the absence of amylase assay harmonization, users must consider the serum concentration or the manufacturer’s suggested reference interval for serum when interpreting results.

Amylase

For LDH, the methods quantify pyruvate except for Ortho, which quantifies LDH activity by the reverse reaction. Overall, the bias observed in BFs is comparable to serum in accordance with the method-specific serum reference intervals Table 1. LDH is measured in BFs to differentiate transudative from exudative or other inflammatory causes of effusion by comparison to serum or expected values in serum,11-13 although in peritoneal fluid a decision limit above 220 U/L is proposed to differentiate secondary from spontaneous bacterial peritonitis.8 We can conclude that while there are statistical differences, the bias appears to be intrinsic to the method and is not specific to specimen type; therefore, the recommendation to compare BF to serum concentration or expected normal concentration should not present any obvious concerns for interpretation. In the case of peritoneal fluid, use of a decision limit should be done with caution using method-specific concentrations.

For lipase, all the assays use different substrate dye combinations to quantify the enzyme activity, and the differences observed correlate with the observed reference values proposed for the assays Table 1. BF lipase interpretation involves comparing the concentration to either the measurement of lipase in serum collected near the time the BF is collected or the comparison to the expected concentration for serum, such as the upper limit of normal for the assay, similar to amylase.14,15 There is a notable bias observed between lipase methods, and it is similar in magnitude between BF and serum, thereby negating the risk for misinterpreting results using a given assay. Similar to amylase, in the absence of lipase assay harmonization, users must consider the serum concentration or the manufacturer’s suggested reference interval for serum when interpreting results.

For bilirubin, all methods used the diazo dye Table 1. The observed differences were relatively minimal (within 1 mg/dL or 10%) between methods, which is consistent with the magnitude of differences observed in other method comparison studies performed with serum.16 BF bilirubin is interpreted either using a decision limit of more than 5 mg/dL or in comparison to measurement in serum.17,18 Differences of 1 mg/dL when used as a decision limit could impart some risk for misinterpretation, but this can be mitigated by interpreting compared with serum concentration.

LDH

For cholesterol, the comparison showed poorer agreement by ANOVA comparison with Ortho compared with other methods, likely due to the significant number of excluded data points below the low limit of quantitation. The methods are expected to be standardized given the National Cholesterol Education Program (NCEP) guidelines used for interpretation, but manufacturers use different standards for traceability Table 1. Prior analysis in serum pools compared several instruments to a reference method, which demonstrated there is negative bias for most methods and that Roche and Abbott (who happen to also use the same dye) have the least bias, which corresponds to our serum comparison findings. Meta-analysis and reviews of studies using cholesterol to detect malignant ascites have proposed a variety of decision limits ranging between more than 40 and 70 mg/dL,1,19 which likely corresponds to the amount of variation observed between methods at this concentration range. It is worth noting that concentrations of cholesterol are higher in serum compared with BFs, and the Ortho and Siemens manufacturer-defined measuring ranges do not extend below 50 mg/dL, which may limit the sensitivity of these assays for detecting malignant ascites. Further studies defining method-specific decision limits are warranted.

For creatinine, all but Beckman in this study use enzymatic methods and are traceable (through primary or secondary standards) to isotope dilution mass spectrometry, whose desirable total allowable error goals and performance are within 7%.20 The Ortho method demonstrates a larger negative bias in drain, peritoneal fluid, and peritoneal dialysate compared with serum when creatinine concentrations are above 3 mg/dL. BF creatinine is interpreted in comparison to serum,21 which could present an issue when using the Ortho method as the bias observed only in BFs may lead to underestimating the BF to serum ratio, particularly in patients with renal impairment whose background creatinine concentration may be elevated. Additional studies are warranted to verify the extent of this risk, as it is dependent on the magnitude of the bias.

For glucose, all methods used hexokinase, except for Ortho using glucose oxidase, which manufacturers have demonstrated achieves desirable total allowable error goals of less than 7%.22 BF glucose is typically measured to identify infection with low concentrations, using decision limits ranging from ~15 to 50 mg/dL, as well as comparison to serum.8,23-26 Since there appears to be a disproportionate bias between BFs (particularly peritoneal fluid) and serum for the Ortho method and Siemens, it is possible that both decision limits and a BF to serum ratio could be underestimated, and those users should exercise caution.

CONCLUSION

For triglycerides, most assays use a similar design, except for Ortho Table 1, although studies have demonstrated they produce rather similar results within ±15% of the reference method.27 Triglycerides are most often interpreted using single decision limits of less than 50 mg/dL, more than 110 mg/dL for pleural fluid, or more than 187 mg/dL for peritoneal fluid.28,29 Overall, the differences were quite small in the BFs tested and not anticipated to affect interpretation.

For urea nitrogen, all assays used a common design, except for Ortho Table 1. Method comparison studies in a serum pool (~12 mg/dL) demonstrated bias less than 1 mg/dL,27 which is comparable to the observed results in both serum and BFs in that concentration range. However, at elevated concentrations, there are more marked differences particularly affecting BFs tested on Ortho. Urea nitrogen concentrations in BFs are often compared with serum concentrations, with elevations indicating presence of urine.21 This could present an issue when using the Ortho method, as the bias is observed only in BFs and may lead to underestimating the BF to serum ratio, particularly in patients with renal impairment whose background blood urea nitrogen concentration may be elevated. Additional studies are warranted to verify the extent of this risk, as it is dependent on the magnitude of the bias.

Acknowledgments

For urea nitrogen, all assays used a common design, except for Ortho Table 1. Method comparison studies in a serum pool (~12 mg/dL) demonstrated bias less than 1 mg/dL,27 which is comparable to the observed results in both serum and BFs in that concentration range. However, at elevated concentrations, there are more marked differences particularly affecting BFs tested on Ortho. Urea nitrogen concentrations in BFs are often compared with serum concentrations, with elevations indicating presence of urine.21 This could present an issue when using the Ortho method, as the bias is observed only in BFs and may lead to underestimating the BF to serum ratio, particularly in patients with renal impairment whose background blood urea nitrogen concentration may be elevated. Additional studies are warranted to verify the extent of this risk, as it is dependent on the magnitude of the bias.

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