Serum Indices: Reduction of clinical errors in laboratory medicine

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Serum Indices:Reduction of clinical errors in laboratory medicineGoing straight for the answer

Serum Indices: Reduction of clinical errors in laboratory medicine 3

cobas® brand

Roche introduces the cobas® brand as the umbrella for products used tocomplete or expand the screening,diagnostic and monitoring applicationsof the professional laboratory.

cobas brand includes:serum work area with clinicalchemistry and immunochemistrydata management and pre-analyticalsolutionsproducts for coagulation analysis andurinalysisinstruments for rapid blood and cardiovascular testingPCR-based applications for virologyand women’s health testing

Clinical errors in laboratory medicineGoing straight for the answer

Content

Preamble . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5Endogenous interferences in laboratory assays . . . . . . . . . . . . . . . . . . . . . . . 7Interference by Hemolysis . . . . . . . . . . . . 8Mechanisms of Interference byhemolysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8Interference by Icterus . . . . . . . . . . . . . . . 10Mechanisms of bilirubin interference . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10Interference by Lipemia . . . . . . . . . . . . . 12Mechanisms of Lipemic interference . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12Endogenous interferences in immunoassays . . . . . . . . . . . . . . . . . . . . . . . . 14Identifying Clinical Errors . . . . . . . . . . 14

Serum Indices . . . . . . . . . . . . . . . . . . . . . . . . . 16How accurate are the Serum-Indices? . . . . . . . . . . . . . . . . . . . . . . . 17Serum Indices - How are they done on cobas c 501 analyzer? . . . . . . 17Advantages of Automated Serum Indices . . . . . . . . . . . . . . . . . . . . . . . . . 20Improved Result Quality and Patient Care . . . . . . . . . . . . . . . . . . . . . . . . . . . 21What does that really mean? . . . . . . . . 23Reagents on the various Roche systems - interference lists:– Roche/Hitachi Systems . . . . . . . . . . . . 24– COBAS INTEGRA® Systems . . . . . . 26– cobas c 501 analyzer . . . . . . . . . . . . . . . . 29Consolidated Workstations . . . . . . . . . . . 31

Medical laboratory tests can be affected by endogenous and exoge-

nous constituents in the sample matrix. The automated objective

determination of the interfering substances provides benefits com-

pared with the subjective visual interpretation. These benefits include

the traceability, efficiency and effectiveness of the work process.

2 Serum Indices: Reduction of clinical errors in laboratory medicine

We want to thank the following people for their contribution and their support:Prof. L. Thomas, E. Gainska, C.A. Mitchell, Q. May

Serum Indices: Reduction of clinical errors in laboratory medicine 54 Serum Indices: Reduction of clinical errors in laboratory medicine

Preamble

The aim of the clinical laboratory is to report the true value of a concen-tration or activity. But the results are often influenced by interfering fac-tors related to the presence of hemoglobin, bilirubin and lipemia, whichmay be recognized by a colored or turbid appearance of the sample. It isdifficult to predict the effect of hemolysis, turbidity (lipemia) and hyper-bilirubinemia because each sample must be visually examined immedi-ately after centrifugation and the potential interfering property recordedin the laboratory journal.

At hemoglobin concentrations exceeding 300 mg/l (18.8 mmol/l), hemolysisis visible to the eye by the red color of the plasma. Hemolyzed samplesare a rather frequent occurence in laboratory practice, with a prevalenceas high as 3.3% and accounting for nearly 60% of rejected samples.

Lipemia is defined as turbidity in serum samples which is visible to thenaked eye. This is usually observed at trigyceride concentrations above300 mg/dl (3.4 mmol/l).

The visual recognition of hyperbilirubinemia is often not sufficientlysensitive. Because of the high absorbance of bilirubin within the range340 to 500 nm and the high background, the linearity range of themethod can become a limiting factor for spectrophotometric analyzes atthese wavelengths.

Of the visible interferences, hemolysis most often affects the major 20clinical chemistry tests, closely followed by total bilirubin and turbidity.Enzyme tests are hardly affected at all. Certain major tests like creatinine,triglycerides, glucose, cholesterol, phosphorus, uric acid, iron, total proteinand bilirubin may be sensitive to the interference of hemoglobin, bilirubinand turbidity.

With the so-called serum indices, the automated determination of potentialinterferences of hemolysis, hyperbilirubinemia and turbidity (lipemia),Roche has created a tool which (i) makes laboratory professionals awareof interferences, (ii) helps to increase the quality of the sample, and (iii)minimizes aberrant test results.

“With the cobas® 6000 analyzer series, the handling of serum indices hasbeen improved further, thereby simplifying the cross check of data andthe identification of affected requests. The work process is thus shorterand safer.”

Prof. Lothar Thomas, Frankfurt, Germany

Introduction

A laboratory error may be defined as “any real or potentially negativeeffect on patient management.”

Laboratory reporting has a great influence on clinical decision making.Laboratory medicine has high performance quality control which areensured by regulatory authorities and certification procedures.

All laboratories make use of statistical quality control procedures toenhance their analytical quality. But, clinical laboratory quality standardsand error detection rates still fall below industrial quality standards.

Many studies (1, 2, 3) have shown that the majority of clinical laboratoryerrors occur in the pre- and post-analytical phases but within the analyti-cal phase, where the minority of errors occur (13-32 %), there may beundetected errors due to the way in which these errors were identified.

Lapworth and Teal (4) reported finding in the literature an overall errorrate of approx. 0.3 % but the authors acknowledged that some errorsmay have gone unnoticed due to the design of the study. Kalra (5) quotesreported error rates of between 0.1–9.3 %. Many studies of error detectionrates do not include erroneous results that were unreported due to theresult fitting other clinical data.

Bonini (6) et al found error rates of 0.60 % in inpatients and 0.039 % inoutpatients

Chambers (7) reported an error rate of 0.3 % in a large laboratory and ear-lier studies by McSwiney and Woodrow (8) found an occurrence of 2.3 %.

Goldschmidt and Lent (9) found that 12.5 % of laboratory errors lead toan erroneous medical decision, 75 % of erroneous results were withinthe reference range and 12.5 % of the erroneous results were so wrong asto be implausible. Plebani and Carraro (1) found that 74 % of laboratoryerrors did not influence patient outcome and 19 % resulted in increasedcosts and/or further investigations. The authors also commented that6.4 % of laboratory errors caused inappropriate care or inappropriatechanges to therapy.

No influence

Further investigations

Inappropriate care

Delays

Potential damage

None

Medical intervention

Impact on patient outcome (Plebani and Carraro)

Impact on patient outcome (Goldschmidt)

6 Serum Indices: Reduction of clinical errors in laboratory medicine Serum Indices: Reduction of clinical errors in laboratory medicine 7

Endogenous interferences in laboratory assays

Plebani and Carraro also found that only 13.3 % of total clinical labora-tory errors were attributed to the analytical phase, but the most commonerrors here were due to interference or lack of sensitivity of the analyticalmethod.

Some aspects of the testing procedure are often outside the laboratory’scontrol and are outside the bounds of typical analytical process control.These may be differences in biological variation, systematic errors andinterfering substances.

Kroll and Elin (10) defined interference as “the effect of a substancepresent in the sample that alters the correct value of the result”.

Medical laboratory tests can be affected by endogenous constituents inthe sample. Some of these may be recognized by a colored appearance ofthe sample (hemolysis, icterus and turbidity) but others (drugs) requiremore detailed information or direct analysis. Interference in an analyticalmethod can produce a false result, which does not reflect the in vivosituation.

Abs

orba

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Wavelength

NADH

Lipemia

Icterus

Hemolysis

340 480

Range 1

505 546 570 600 660 700 (nm)

Range 2 Range 3

Chemical InterferenceBlood cell constituents can interfere directly or indirectly in the meas-urement of analytes. Adenylate kinase released from erythrocytes maycause an increase of creatine kinase and CK-MB activity.

Free hemoglobin with its pseudo-peroxidase activity interferes in thebilirubin procedure of Jendrassik and Grof by inhibiting the diazoniumcolor formation. Proteases released from blood cells reduce the activityof coagulation factors and fibrin split product formation may increase.

Hemoglobin may also interfere by reacting with one or more constituentsof the reagent and the interference may differ with different reagentsources.

Hemolytic Interference?! - Sample operation with interference check on cobas® 6000 analyzer series; Prof. L. Thomas

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In vivo Hemolysis(Haptoglobin:

low or 0)

Application datavia cobas® link

Serum Indexdetermination of the

individual sample

S.I. sample value:

H-index

Sample: H-result: < ? > ? as

specified limit

Sample: H-result < asspecified limit

Sample: H-result > asspecified limit

All patient sampleswith hemolysis

Individual samplewith Hemolysis

+ Haptoglobin normal

Request for new sample

“Results are disturbed in a clinical relevant way; espc.

K, Phos, LDH, AST, NSE!

Result validated,report of result


Interference by Hemolysis

Plasma samples with increasing degrees of hemolysis Differences in the individual appearance is hard to distinguish from level to level (Increase of inter-

ference level in steps of 100, starting from “zero”)

Hemolysis is defined as the release of intracellular components fromerythrocytes and other blood cells into the extra cellular fluid and can becaused by many mechanisms.

Hemolysis may be in vivo as the result of biochemical, immunological,physical or chemical mechanisms. More commonly hemolysis is in vitroand is usually caused by inappropriate or incorrect sample processing.Even if hemolysis is not visible there may still be discharge of cellularcontents into the serum/plasma.

A study by Carraro and Plebani found that up to 3.3 % of all specimensreceived by the laboratory were hemolyzed. It is widely accepted thathemolysis can be a source of error in many chemical analyses.

Mechanisms of Interference by hemolysis (11, 12, 13)

Rise of intracellular constituents in the extra-cellular spaceSome cell constituents have an intra-cellular concentration 10 times higherthan the extra-cellular concentration. Hemolysis in the plasma/serumwill cause an increase in concentration of these analytes (for example,potassium, lactate dehydrogenase, aspartate aminotransferase).

Spectral interferenceHemoglobin absorbs light very strongly at its characteristic wavelengthof 415 nm. The effect of hemolysis on various analytes measured in clini-cal chemistry has been thoroughly investigated. The observed increase ordecrease of a result by hemoglobin has been found to be dependent onmethod and analyte concentration.

Dilution-level Tube # n 0 1 2 3 4 5 6 7 8 9 10Index H 0 100 200 300 400 500 600 700 800 900 1000

Icteric Interference?! - Sample operation with interference check on cobas® 6000analyzer series; Prof. L. Thomas


individual sample

1+1 dilution of sample with purified

serum albumin (40g/L)

Report result


No interference with analyte

S.I. sample value:

I-index

Does bilirubininterfere with

analyte?

Analyte has interference limit for bilirubin:

Specified limit is indicated

I-index below specified limit – no interference occured

I-index above specified limit

Report of resultResult to be

multiplied by 2 report result

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Interference by Icterus

Plasma samples with increasing degrees of icterusRetrievable differentiation can be performed with automated process – to distinguish the individual

appearance can potentially classify the sample in another level (Increase of interference level in steps

of 6.6, starting from “zero”)

Elevated concentrations of bilirubin are another source of endogenousinterference. Such elevations can be found in a variety of conditionsincluding acute and chronic liver disease, biliary cirrhosis, alcoholism oras a physiological response to many drugs.

Mechanisms of bilirubin interference (11, 12)

Spectral interferenceBilirubin absorbs strongly between 340 nm and 500 nm wavelengths andthe high background absorbance can lead to absorbance readings inexcess of the linearity of spectrophotometric procedures.In a strongly acidic solution the absorption of conjugated bilirubin shiftsto the UV wavelengths. Therefore bilirubin interferes in the determinationof some analytes that use these wavelengths. Under alkaline conditionsbilirubin is oxidized and loses some of its absorption properties.

Chemical interferenceBilirubin may interfere by acting as a reducing substance as it is easilyoxidized to biliverdin and bilipurpurin with a reduction in absorbance.Assays that utilize oxidase/peroxidase based reactions to produce hydrogenperoxide, may produce lower results because bilirubin reacts with theH2O2 formed in the test system. The reduction in H2O2 is relative to theconcentration of bilirubin present. This is true for enzymatic proceduresthat are used for the measurement of glucose, cholesterol, triglyceridesand uric acid.In albumin assays that employ dye binding, bilirubin can competitivelybind to the dye and produce lower albumin results.


Dilution-level Tube # n 0 1 2 3 4 5 6 7 8 9 10Index I 0 6.6 13.2 19.8 26.4 33.0 39.6 46.2 52.8 59.4 66.0

Volume depletion effectLipoproteins have a “solvent displacing effect” on sampling by reducingthe available water of the sample volume. Most analytes are dissolved inthe aqueous phase of the plasma/serum. Thus, the effect is to decreasethe apparent concentration of the analyte because the volume occupiedby lipoproteins in plasma or serum is included in the calculation of theanalyte concentration. For analytes that are lipid soluble, including certaindrugs that are taken up by lipoproteins, there is an apparent increase inconcentration.

Physico-chemical effectsAn analyte that is soluble in lipids may not be accessible to the reagentfor reactivity. Similarly, electrophoretic and chromatographic proceduresmay be affected by lipoproteins present in the matrix.

Lipemic Interference?! - Sample operation with interference check on cobas® 6000analyzer series; Prof. L. Thomas

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individual sample

S.I. sample value:

L-index

Does lipemiainterfere with

analyte?

Method 1 + 2 Failed - high speed centrifu-

gation: possible?!

YES: Centrifugation

> 40000g x 30min

YES (2): S/PI mix 1+1with PEG 6000 -

incubate 30min at 4°C- centrifuge 1000g x 10min

Blood sampling: after12h fasting + after 8h

infusion of lipids

Start processfrom beginning

YES (1): centrifugation(12000g x 10min)

S/PI lipid separation

Separate clearsupematant analyte

Report resultNO:

Request of new sample

Determinationand report of

result

Interference by Lipemia

Plasma samples with increasing degrees of turbidity Any changes in the individual appearance from level to level might hardly be distinguished

(Increase of interference level in steps of 200, starting from “zero”)

Lipemia is defined as turbidity in samples which is visible to the nakedeye. The most common cause of turbidity is an increased concentrationof triglycerides. Lipemic samples cannot be avoided as increased concen-tration of lipids is often secondary to other disease states such as: diabetesmellitus, ethanol use, chronic renal failure and pancreatitis etc.

Mechanisms of Lipemic interference (11, 12, 14, 15)

Spectral interferenceThe interference caused by lipemia is fundamentally different from theinterference from hemolysis and icterus. Lipemia interferes by scatteringthe light and disturbing (absorbing) the transmission of light throughthe reaction mixture. In lipemia there is a number of lipid componentsthat can scatter light to produce a milky appearance or turbidity.The degree of light scattering depends on the number, size and refractiveindex of the suspended lipid particles. As patient serum samples are amixture of various particle sizes, the sample appears white because thelight is scattered at all angles.

Larger lipid entities such as chylomicrons and VLDL cause light to bescattered to the greatest degree. Chylomicrons constitute a diverse groupof particles with varying sizes and vary from individual to individual.VLDL particles are a heterogeneous mixture of sizes and lipid content andthe number of VLDL particles can be increased in various disease states.

The interference can be either positive or negative depending on theblanking procedure of the assay. At high turbidity, no measurement maybe possible due to the limits of the linearity of the spectrophotometer.


Dilution-level Tube # n 0 1 2 3 4 5 6 7 8 9 10Index L 0 200 400 600 800 1000 1200 1400 1600 1800 2000

Endogenous interferences in immunoassays

Immunoassays may be susceptible to the same endogenous interferencesas mentioned above if the measuring system used is photometric such asfor enzyme linked immunoassay or fluorescence immunoassay.

Roche analyzers have a measuring system that employs heterogeneouschemilluminscence, which is less prone to these interferences, althoughsome immunoassays may still have interference from unusual serum con-stituents.

Immunoassays employ antibodies to specific proteins and rely on thebinding of these antibodies to the antigen. Unusual proteins in thepatient sera, for example, endogenous heterophilic antibodies such asrheumatoid factor, anti-animal antibodies or other non-specific antibod-ies may interfere in the binding process.

Hemolysis interference in immunoassays may be caused by constituents ofred blood cells being released into the serum/plasma. These constituentsmay influence antibody-antigen binding and produce lower or higherresults depending on where they interfere in the reaction.

Interference from Icterus in immunoassays is not common because thewavelengths employed in chemilluminescent technology are separatedfrom the absorbance maxima of bilirubin.

Lipemia interference in immunoassays relates to the solubility of theantigen to be measured in lipid and is therefore no longer available tobind with the antibody.

Identifying Clinical Errors

It is the responsibility of the laboratory to produce true and accurateresults and to decrease or avoid completely those with a real or potential-ly significant negative effect on patients’ health.

Because laboratory errors caused by interferences are rare, it is difficultto detect and prevent them from being reported. Many errors may not

necessarily produce detectable abnormal results or raise questions for theclinician. Errors caused by interfering substances cannot be detected orprevented by the use of statistical QC procedures. Such procedures canonly control process (analytical) variations. Results released from “in-control” runs may contain spurious results that are not detected.

In a study conducted by Glick (16) in an acute care hospital he deter-mined the frequency with which turbidity, hemolysis or icterus wasencountered in serum samples. 32 % of all samples were found to havemore than trace concentrations of an interferent. Of these, approximately63 % were icteric, 29 % hemolyzed and 8 % lipemic.

Ryder (17) studied serum from outpatients and found that 9.7 % ofspecimens received contained at least one visible interferent. Of these,76 % were lipemic (probably because of non-fasting state), 16.5 % werehemolyzed and 5.5 % were icteric.

Frequency of Endogenous Interferences

Therefore to prevent the reporting of erroneous results every sampleshould be evaluated for the possibility of interference. The consequenceis the improvement of the quality of the service provided and improve-ments in patient care by reducing false results that can occur from inter-ferences.

%

Lipemia0

20

40

60

80

Hemolysis Icterus

Inpatient

Outpatient


Within the manufacturing industry, Shingo (18) showed that because ofthe rare nature of errors, they can only be controlled with 100 % inspec-tion but this must be easy and inexpensive. He also reports that theinspection must be upstream of the product before it results in an error,which is before the result is released.

Hinkley (19) observed that human inspection methods failed to detectmost errors. Glick (16) found that the visual interpretation of hemolysis,lipemia and icterus showed very little agreement to the actual concentra-tion of interferent. Even when comparison samples are used, visual grad-ing was still problematic. He noted that because of this inconsistency anunbiased method is required to quantitate the level of interference.

Serum Indices

Serum indices are calculations of absorbance measurements that providea semi-quantitative representation of levels of icterus, hemolysis, orlipemia that are present in unknown samples. Thus the quality of thesample is assessed at the same time as the sample is processed.

Roche analyzers have been capable of semi-quantitative measurementand reporting of the Serum-Indices since the early 1980s using 9 % NaClas reagent.

The bichromatic wavelength pairs used for serum index measurementare 480 nm and 505 nm (range 1), 570 nm and 600 nm (range 2), and660 nm and 700 nm (range 3). Calculation formulas include correctionsto compensate for the spectral overlap.

How accurate are the Serum-Indices?

Lipemia and Intralipid®The Lipemic Index L is measured in lipemia units and is based on theoptical behaviour of the lipid substitute Intralipid (L units are linear upto 2000 mg/dL). The Lipemic Index provides an estimate of sample tur-bidity, not the concentration of triglycerides. This is because the lipemicIndex is a measure of light scatter, which is dependent on particle size.

Hemolysis and hemoglobinRecovery of the Hemolysis Index correlates well with the hemoglobinconcentration in the patient’s sample depending on the method used tomeasure Hb.

Icterus and bilirubinRecovery of the Icteric Index correlates well with the bilirubin concen-tration in the patient’s sample.


Serum Indices - How are they done on cobas c 501 analyzer?

Serum indexes are calculations of absorbance measurements that providea semiquantitative representation of levels of icterus, hemolysis orlipemia (turbidity) present in patient samples.

A quantification of these interfering materials is possible with the SerumIndex Gen.2 (SI2) application which can be installed on all cobas c systems.When measuring Serum Indices, the analyzer takes an aliquot of thepatient sample (cobas c 501 analyzer takes 6 µl), dilutes it with 0.9% NaCl,and then measures the absorbances at three pairs of wavelengths:1. For measurement of lipemia (L), wavelengths 700/660 nm are used

because this range is free from influence by hemolysis and icterus (seefigure page 7).

2. Hemolysis (H) is measured at 600/570 nm and correction is made forabsorption due to lipemia.

3. Icterus (I) is measured at 505/480 nm and correction is made forabsorption due to lipemia and hemolysis.


If measured values are higher than specified limits of the individual test,the analyzer issues alarms for the measured results: “Serum 1” - for oneindex higher, “Serum 2” - when two or all three indices are higher thantheir limits.The benefit for the user: if the results are affected by endogenous sampleinterference – there is no need to manually crosscheck the pack insert forthe index level nor is an additional LIS check needed.

Serum index limits are provided as a part of the application. Applicationdata is downloaded electronically via a remote access tool, called cobas®link. Potential updates are provided on a daily basis. No manual interac-tion (such as typing in application data from an application sheet) isrequired. The user initiates the download of the data from cobas® link tothe analyzer.

Serum index results are very useful for monitoring the degree of potentialinterference due to lipemia (turbidity), hemolysis and icterus (bilirubin)and therefore

improves the quality of reported results: 100% of samples are checked in almost no time: One simple pipetting step in the analytical phasereplaces both the visual check in the pre-analytical phase and theretrieval of suspicious samples in the post-analytical phasewith minimal cost: only the use of a simple NaCl solution compared tomanually intensive tasks in the pre and post-analytic phasesimproved handling of pediatric samples: enabling efficient and reliablehandling of very small sample volumes

For performing Serum Index check on the cobas c 501 analyzer theoperator needs to apply some easy steps:

download Serum Index (SI2) application (via cobas® link)cross-link SI application with pre-installed H, I and L applicationscalibrate SI (only one blank calibration is required per reagent lot)request SI together with other test requests for a serum sample

Serum indices can be programmed in either conventional or SI units.

Each report on laboratory findings should contain a notation character-izing the sample’s “appearance”. “If lipemia or a relevant color is found,the cobas c 501 analyzer will indicate, in each case, the type of finding(L)-index “lipemic”, (H)-index “hemolytic” and (I), index for “icteric”.”

The diagram shows an example absorption spectra of a turbid serum, ahemolytic solution, and a bilirubin solution.

Once the serum indexes are determined, cobas c 501 analyzer comparesthem with the H, I and L limits given in each individual test application.The limits are indications below which potential interference is consideredclinically not relevent.

Abs

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Wavelength

Bilirubin solution

Lipemic serum

Hemolytic solution

340 480 505 546 570 600 660 700 (nm)

Decreased CostsWith less operator time involved in examining suspicious samples notonly TAT is decreased but the costs involved in repeating “out of limit”results due to interferences are reduced. The serum index result reportedsimultaneously with the test result enables the operator to acknowledgethe presence of interfering substances as the potential cause of the “abnor-mal” result and removes the need to rerun the sample, thus reducing costs.

Improved Result Quality and Patient Care

Vermeer (20) in 2005 reported on improvements in patient results withrespect to endogenous interferences by the introduction of an automateddetection and reporting system. The laboratory information system (LIS)used a rule-based algorithm to assess the effect of interference on eachanalyte measured.

Test-specific serum index decision thresholds were used to:Detect interferenceAlert the operator Add appropriate commentsReject a result where necessary

Advantages of Automated Serum Indices

Advances in technology allow Roche to incorporate an automated featureinto their analytical instruments to verify the quality of the specimen atthe same time as the result is produced.

Up to now, medical laboratories have taken a “judgment inspection”approach to endogenous interferences; the operator decides whether thesample is appropriate or not. If an abnormal result is obtained, the sampleis inspected for visible interferences. Thus judgment inspections can onlydetect errors after they have been made and identified.

Decreased Turnaround Time (TAT)Manual inspection may be performed on every specimen before analysis(pre-analytical) or inspecting specimens that produce “suspect” results(post-analytical). This is very time consuming and as previously reported,this produces very inconsistent results. In addition a “normal” result doesnot create suspicion.

When Serum Indices are produced by the instrument, consistent evaluationsare made and remove the potential for human error and save operator time.

Turn Around Time

Thus: a slight increase in analytical time but a large decrease in pre-and/or post-analytical time – reduced TAT


Pre-analytical Phase Analytical Phase Post-analytical Phase

Sample inspectionof dubious samples

(A) Manual Sample Inspection in Pre/Post-Analytical Phase

Sample inspectionof dubious results

Pre-analytical Phase

Analytical Phase Post-analytical Phase

(B) Serum Index incorporated into Analytical Phase

Automatic inspectionof ALL samples

Sample LIS*

* cobas® 6000 analyzer series in software* Roche/Hitachi Analyzer / COBAS INTEGRA® = LIS

Result

Addcomment

AlertOperator

Releaseresult

H index L index I index

What does that really mean?

Of all the samples received by the laboratory as many as 22 % may beinfluenced by endogenous interferences. The chance of identifying a possiblevisible interferent is greatly decreased when primary tubes are covered withseveral labels which prevent the clear inspection of the sample.

A serum index result generated simultaneously with the sample resultensures that all samples are correctly identified.

Reporting results that acknowledge the effect of interferences, gives resultsthat are appropriate to the quality of the sample, thus avoiding inaccurateresults as a consequence of the interference.The improved clinical usefulness of the result allows better clinical decisionsand better patient care.Manufacturers of instruments and analytical methods by the FDA andunder the IVD directive are requested to provide details of the degree ofinterference for each assay. Roche conducts the interference studiesaccording to the guidelines of the NCCLS (EP7-P).

They found that by introducing the rule-based system, the detection rateof clinically significant hemolysis increased approximately 70 fold, icterus10 fold and lipemia over 1000 fold.

Glick (22) interferographs are produced for all assays. This is an easilyunderstandable graphical display of the interference data showing thedeviation from the original result caused by the interferent.The level of interference producing a clinically significant difference isindicated in the Roche pack insert.

Effect of Serum Index and LIS

Rec

over

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kno

wn

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l

100 %

90 %

110 %

H > 700IncreasingH index value

Glick interferograph

!

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Manual inspection1

10

100

1000

10’000

Automated SI LIS Processing

Hemolysis

Icterus

Lipemia


Reagents on Roche/Hitachi Systems

List of interferences1 based on serum indices for serum and plasma (not applicable for urine)

Analyte Sample Material

Interference withinspecification up to

(conventional units):

~mg/dl ~mg/dl ~mg/dl ~µmol/l ~µmol/l ~µmol/l Turbidity


(SI units):

withoutunits1

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ACP Acid Phosphatase X � � � � 1 1 100 17 17 62 200ACP-NPP Non-prostatic Acid Phosphatase X � � � � 1 1 100 17 17 62 200Albumin plus Albumin X X X �� 60 60 1000 1026 1026 621 1000Albumin Tina-quant® Albumin (turbidimetric) X X X �� 60 60 1000 1026 1026 621 1000ALP IFCC liquid Alkaline phosphatase IFCC X X �� 70 70 500 1197 1197 310 2000ALP opt Alkaline phosphatase opt X X � �� 60 60 1000 1026 1026 621 1000ALT/GPT IFCC Alanine Aminotransferase IFCC X X X �� 60 60 60 1026 1026 37 500Ammonia Ammonia X �� n/a 60 60 50 1026 1026 31AMYL liquid α-Amylase X X X �� 60 60 500 1026 1026 310 1500P-AMYL liquid α-Amylase Pancreatic X X X �� 60 60 500 1026 1026 310 1500APOA1 Tina-quant® Apolipoprotein A-1 X X X �� 60 60 1000 1026 1026 621 1000APOB Tina-quant® Apolipoprotein B X X X �� 60 60 1000 1026 1026 621 1000ASLO Tina-quant® Antistreptolysin O X X X � �� 26 26 1000 445 445 621 1000AST/GOT IFCC Aspartate Aminotransferase IFCC X X X �� 60 60 25 1026 1026 16 500ATIII Antithrombin III X �� 29 29 1000 496 496 621 1250a1-Antitrypsin α1-Antitrypsin X X X X �� 60 60 1000 1026 1026 621 890b2-Microglobulin β2-Microglobulin X X X � �� 54 54 1000 923 923 621 750BICARB liquid Bicarbonate X X � � �� 60 60 1000 1026 1026 621 2000BILI-Total DPD Bilirubin Total X X X n/a n/a � � n/a n/a 10 n/a n/a 6 75TBILI liquid Bilirubin Total liquid X X X n/a n/a � � n/a n/a 1000 n/a n/a 621 1000C3c Tina-quant® Complement C3c X X X �� 60 60 1000 1026 1026 621 1000C4 Tina-quant® Complement C4 X X X � �� 60 60 900 1026 1026 559 1000Ca Calcium X X �� 60 60 1000 1026 1026 621 1000CARB II CEDIA® Carbamazepine X X X �� 60 60 1000 1026 1026 621 1000CDT Tina-quant® Carbohydrate Deficient Transferrin X �� 60 60 1000 1026 1026 621 750CHE butyryl Cholinesterase X X X �� 60 60 850 1026 1026 528 1250CHOL Cholesterol X X X � � � �� 25 10 700 428 171 435 1250CK liquid Creatine Kinase X X X �� 60 60 100 1026 1026 62 1000CK-MB liquid Creatine Kinase-MB X X X �� 60 20 20 1026 342 12 600Ceruloplasmin Tina-quant® Ceruloplasmin X X X �� n/a 60 60 1000 1026 1026 621Crea Creatinine Jaffé

rate blanked + compensated X X X � � � �� 10 10 750 171 171 466 1000Crea Creatinine Jaffé STAT compensated X X X � � � �� 4 4 750 68 68 466 1000Crea plus Creatinine enzymatic X X X � � �� 25 25 1000 428 428 621 1000CRPLX Tina-quant® C-Reactive Protein (latex) X X X �� 60 60 950 1026 1026 590 1700CRPHS Tina-quant® C-Reactive Protein (latex)

high sensitive X X X �� 60 60 1000 1026 1026 621 500 (2mg/l)

CRPHS Tina-quant® C-Reactive Protein (latex)high sensitive X X X �� 60 60 1000 1026 1026 621 800 (4mg/l)

CRPHS Tina-quant® C-Reactive Protein (latex)high sensitive X X X �� 60 60 1000 1026 1026 621 1000 (5mg/l)

D-Bil Jendrassik Bilirubin Direct (Jendrassik) X X X n/a n/a � � n/a n/a 25 n/a n/a 16 140D-Dimer Tina-quant® D-Dimer X � �� 20 20 500 342 342 311 1500Digoxin II CEDIA® Digoxin X X X � � �� 60 60 1000 1026 1026 621 1000Digoxin Tina-quant® Digoxin X X X � � � � 60 60 1000 1026 1026 621 850Digitoxin CEDIA® Digitoxin X X �� 60 60 1000 1026 1026 621 1000Digitoxin OnLine Digitoxin X X �� 60 60 601 1026 1026 373 1768Ethyl Alcohol Ethanol (904/911/912/917) X X X X �� 60 60 200 1026 1026 124 500Ethyl Alcohol Ethanol (902) X X X X �� 60 60 100 1026 1026 62 500Ethyl Alcohol Ethanol (Modular) X X X X �� 60 60 1000 1026 1026 621 500Fe Iron X X �� 60 60 80 1026 1026 50 1000FERRI Tina-quant® Ferritin X X X X �� 60 60 500 1026 1026 311 750FRUCT Fructosamine X X X � � � �� 5 5 500 86 86 311 1000

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Intralipidnot measured






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Gentamycin OnLine Gentamycin X X X �� 60 60 1350 1026 1026 838 170GGT liquid γ-Glutamyltransferase X X X �� 20 20 200 342 342 124 1000GGT HiCo liquid γ-Glutamyltransferase X X X �� 50 20 200 855 342 124 1000GLDH Glutamate Dehydrogenase X X X � � � n/a 60 60 10 1026 1026 6GLU HK Glucose (Hexokinase) X X X X �� 60 60 1000 1026 1026 621 1000GLU GOD PAP Glucose (GOD PAP) X X X X � � � � 22 20 850 376 342 528 150GPROT Tina-quant® α1-Acid Glycoprotein X X X �� 60 60 1000 1026 1026 621 750HBDH Hydroxybutyrate Dehydrogenase X X X �� 60 60 10 1026 1026 6 600HDL-C plus 2nd gen. HDL-Cholesterol X X �� 30 70 1200 513 1197 745 1000HAPT Tina-quant® Haptoglobin X X X �� n/a �� 60 60 n/a 1026 1026 n/a 1000IGA Tina-quant® Immunoglobulin A X X X �� 60 60 1000 1026 1026 621 600IGA Tina-quant® Immunoglobulin E X X X X �� 60 60 1000 1026 1026 621 600IGA Tina-quant® Immunoglobulin G X X X �� 60 60 1000 1026 1026 621 600IGA Tina-quant® Immunoglobulin M X X X �� 60 60 1000 1026 1026 621 600Kappa Tina-quant® Kappa Light Chains X X X �� 60 60 500 1026 1026 311 500Lactate Lactate X � � �� 28 60 1000 479 1026 621 1000Lambda Tina-quant® Lambda Light Chains X X X �� 60 60 500 1026 1026 311 500LDH opt Lactate Dehydrogenase opt X X X �� 60 60 10 1026 1026 6 900LDH IFCC liquid Lactate Dehydrogenase IFCC X X �� 60 60 10 1026 1026 6 1000LDL-C plus 2nd gen. LDL-Cholesterol X X �� 39 70 1500 667 1197 931 200LIP colorimetric Lipase X X �� 60 60 500 1026 1026 311 1000LP(a) Tina-quant® Lipoprotein (a) X X X � �� n/a 60 60 500 1026 1026 311MG Magnesium X X �� 65 37 400 1112 633 248 400Myoglobin Tina-quant®Myoglobin X X X X � � � � 60 60 500 1026 1026 311 450NAPA CEDIA® N-Acetyl Procainamide X X X �� 60 60 1000 1024 1024 621 1000Prealbumin Tina-quant® Prealbumin X X X �� 60 60 500 1026 1026 311 200PHENO CEDIA® Phenobarbital X X X �� 60 60 1000 1026 1026 621 1000PHENY OnLine Phenytoin X X X �� 60 60 1000 1026 1026 621 800PHOS UV Phosphate (inorganic) X X X X � �� 35 62 300 599 1060 186 1250PROC CEDIA® Procainamide X X X �� 60 60 1000 1026 1026 621 1000QUIN OnLine Quinidine X X X �� 65 65 1000 1111 1111 621 2000RF II Tina-quant® Rheumatoid Factors X X X �� 60 60 1000 1026 1026 621 400Salicylate Salicylate X �� 60 100 1026 62 500sTfR Tina-quant® Soluble Transferrin Receptor X X �� 60 60 1000 1026 1026 621 1000T Uptake CEDIA® T Uptake X X X �� 60 60 1000 1026 1026 621 1000T4 CEDIA® Total T4 X X X � � � � 60 60 550 1026 1026 342 1000TP Total Protein X X X � � � � 21 21 650 359 359 404 1000TG Triglycerides X X X � � � n/a 10 27 500 171 462 310 n/aTHEO OnLine Theophylline X X X �� 45 60 1450 770 1026 901 333TOBR II CEDIA® Tobramycin X X X � �� 60 1000 1026 621 1000Transferrin ver. 2Tina-quant® Transferrin X X X �� 60 60 1000 1026 1026 621 500UA plus Uric Acid X X X � � � �� 40 40 1000 684 684 621 1000UIBC Unsaturated Iron Binding Capacity X X � � � 60 60 200 1026 1026 125 100Urea liquid Urea X X X �� 60 60 1000 1026 1026 621 1000VPA II CEDIA® Valproic Acid X X X �� 60 1000 1026 621 1000

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Intralipidnot measured

n/a = not applicable� = over-recovery� = under-recovery�� = variable recovery�� = recovery within ±10 % of initial concentration1 Interferences were tested with the following substances added to samples:

Hemoglobin up to 621 µmol/l (1000 mg/dL)Bilirubin up to 1026 µmol/L (60 mg/dl)Lipemia up to 20 g/l Intralipid® (2000 mg/dl). Lipemia has no units as it is a measure of turbidity.Only significant interferences (> 10 %) are listed in the method sheetsReference: Glick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470–474.

2 L index not measured with Intralipid®, interference measured as Triglycerides (see package insert)3 Endogenous bilirubin samples were used, total bilirubin was measured







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CRPL2 C-Reactive Protein (Latex) INTEGRA 700/800Application for C.f.a.s. Proteins X X X �� no no no no no no 797 (80mg/l)

D-DI D-Dimer X X �� no no 300 no no 186 600DIG3 Digoxin X X � � � n/a 25 25 2000 428 428 1242DIGIT3 Digitoxin X X �� n/a 19 19 1000 325 325 621ETOH2 Ethanol Gen.2 X X X �� no no no no no no noFERR2 Ferritin Gen.2 X X �� no no 960 no no 596 160FPHNY3 Free Phenytoin X X �� n/a 26 26 1000 445 445 621FRA Fructosamine X X X � � � �� 5 5 50 85 85 31 noFVALP3 Free Valproic Acid X X �� n/a 27 27 1000 462 462 621GENT3 Gentamicin X X � � � n/a 15 15 1000 257 257 621GGTI2 γ-Glutamyltransferase ver.2

Standardized against IFCC X X X �� no 48 550 no 821 342 noGGTS2 γ-Glutamyltransferase ver.2

Standardized against Szasz X X X �� no 48 550 no 821 342 noGLDH3 GLDH Gen.3 Utility Cassette Set X X X � � � n/a 22 54 10 376 923 6GLUC2 Glucose HK X X X X �� no no no no no no noGLUCL Glucose HK Liquid X X X X �� no no no no no no noHAPT2 Haptoglobin ver.2 X X X �� n/a �� no no n/a no no n/a 1600HBDH2 HBDH Gen.2 Utility Cassette Set X X X �� no no 25 no no 16 700HDL_C HDL-Cholesterol plus 2nd generation X X X �� 24 24 1500 410 410 932 noIGA Immunoglobulin A X X X �� no no no no no no 750IGGT Immunoglobulin G (Turbidimetric) X X X X �� no no no no no no noIGM Immunoglobulin M X X �� no no no no no no 150IRON Iron X X � � � � 40 40 500 684 684 311 120LACT2 Lactate Gen.2 X � �� 18 no no 308 no no noLDHI2 Lactate Dehydrogenase acc. IFCC ver.2 X X �� no no 10 no no 6 noLDHL Lactate Dehydrogenase (P-L) X X �� no no 10 no no 6 120LDHPL Lactate Dehydrogenase (P-L)

Primary Tube X X �� no no 10 no no 6 120LDIP2 Lactate Dehydrogenase acc. IFCC ver.2

Primary Tube X X �� no no 10 no no 6 noLDL-C LDL-Cholesterol plus 2nd generation X X X �� 40 40 1000 684 684 621 400LIDO3 Lidocaine X X � � � n/a 18 18 1000 308 308 621LIPC Lipase colorimetric X X �� no no no no no no noLPALX Lipoprotein (a) (Latex) X X X �� no no no no no no noMG Magnesium X X �� no no 550 no no 342 noMYO Myoglobin X X X �� no no no no no no 100NAPA3 N-Acetyl-Procainamide X X � � � n/a 28 28 1000 479 479 621NH3L Ammonia X � � � n/a 11 11 100 188 188 62PHNO3 Phenobarbital X X �� n/a 38 38 1000 650 650 621PHNY3 Phenytoin X X � �� n/a 29 29 1000 496 496 621PHOS2 Phosphate (Inorganic) ver.2 X X X � �� 51 no 420 872 no 261 1000PREA3 Prealbumin INTEGRA 400

Application for C.f.a.s. PAC X �� no no no no no no 120PREA3 Prealbumin INTEGRA 700/800

Application for C.f.a.s. PAC X �� no no no no no no 169PRIM3 Primidone X X � � �� n/a 18 18 1000 308 308 621PROC3 Procainamide X X �� n/a 19 19 1000 325 325 621QUIN3 Quinidine X X �� n/a 24 24 1000 410 410 621RF-II Rheumatoid Factors II X X X �� no no no no no no noSALI3 Salicylate X X �� n/a 23 23 1000 393 393 621SBARB3 Serum Barbiturates X X � � �� n/a 24 24 1000 410 410 621SBENZ3 Serum Benzodiazepines X X � � �� n/a 23 23 1000 393 393 621

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Intralipidnot measured2















underevaluation

under evaluation

Reagents on COBAS INTEGRA® Systems







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AAGP α1-Acid Glycoprotein X X �� no no no no no no noAAGP2 α1-Acid Glycoprotein Gen.2 X X X �� 60 60 1000 1026 1026 621 700AAT2 α1-Antitrypsin ver.2 X X X �� no no no no no no 1200ACETA3 Acetaminophen X X � � � n/a 13 13 400 222 222 248ACPP Acid/Prostatic Phosphatase X � � � � 0.7 0.7 10 12 12 6 270ALB2 Albumin Gen.2 X X X �� no no 420 no no 261 noALBS Albumin (Turbidimetric)

Serum Application X �� no no no no no no noALP2 ALP IFCC Gen.2 X X �� no no 250 no no 155 noALTL Alanine Aminotransferase X X X �� no no 130 no no 81 noALTPL Alanine Aminotransferase

Pyridoxal Phosphate Activated X X X �� no no 130 no no 81 noAMIKM3Amikacin X X � � � n/a 18 18 1000 308 308 621AMYL2 α-Amylase EPS ver.2 X X X � �� 52 no 260 889 no 161 noAMY-P α-Amylase EPS Pancreatic X X � � � �� 17 17 100 300 300 62 noAP2P ALP IFCC Gen.2 Primary Tube X X �� no no 250 no no 155 noAPOAT Apolipoprotein A-1 ver.2 X X X �� no no no no no no 1000APOBT Apolipoprotein B ver.2 X X X �� no no no no no no 1000ASO2 Antistreptolysin O

Application for C.f.a.s. PAC X �� no no no no no no 1500ASTL Aspartate Aminotransferase

Pyridoxal Phosphate Activated X X X �� no no 25 no no 16 noASTPL Aspartate Aminotransferase

Pyridoxal Phosphate Activated X X X �� no no 25 no no 16 noAT Antithrombin X �� no no no no no no noBIL-D Bilirubin Direct X X n/a n/a � � n/a n/a 10 n/a n/a 6 270BIL-T Bilirubin Total X n/a n/a � � n/a n/a 10 n/a n/a 6 9BILTS Total Bilirubin Special X X X n/a n/a � � n/a n/a 1000 n/a n/a 621 1400C3C-2 Complement C3c ver.2 X X �� no no no no no no noC4-2 Complement C4 ver.2 X X X �� no no no no no no noCA Calcium X X �� no no no no no no noCARB3 Carbamazepine X X �� n/a � n/a 20 20 750 342 342 466CERU Ceruloplasmin X X �� no no no no no no 50CERU2 Ceruloplasmin

Application for C.f.a.s. Proteins X X �� no no no no no no 50CERU3 Ceruloplasmin

Application for C.f.a.s. PAC X X �� no no no no no no 50CHE Cholinesterase X X X �� no no no no no no noCHE-D Cholinesterase/Dibucaine X X X �� no no no no no no noCHOL2 Cholesterol Gen.2 X X X � � � �� 16 11 810 274 188 503 noCKL Creatinine Kinase X X � � � �� 15 15 100 255 255 62 noCKMBL Creatinine Kinase-MB X X � � � � 20 20 10 340 340 6 500CO2-L Bicarbonate liquid X X �� no no no no no no noCREJC Creatinine Jaffé Integra 400

Comp. Method for Serum and Plasma X X X � � � � 5 5 800 85 85 497 250CREJC Creatinine Jaffé Integra 700/800

Comp. Method for Serum and Plasma X X X � � � � 5 5 400 85 85 248 250CREP2 Creatinine plus ver.2 X X X � � � � 20 20 800 340 340 497 1000CRPL2 C-Reactive Protein (Latex) Integra 400

Application for C.f.a.s. Proteins X X X �� no no no no no no 1500 (3mg/l)

CRPL2 C-Reactive Protein (Latex) Integra 400Application for C.f.a.s. Proteins X X X �� no no no no no no 623 (80mg/l)

CRPL2 C-Reactive Protein (Latex) Integra 700/800Application for C.f.a.s. Proteins X X X �� no no no no no no 1094 (3mg/l)

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STFR Soluble Transferrin Receptor X X �� no no no no no no noT43 Total T4 (Thyroxine) X X �� n/a 15 15 1000 257 257 621THEO3 Theophylline X X �� n/a 29 29 1000 496 496 621TOBR3 Tobramycin X X �� n/a 13 13 1000 222 222 621TP2 Total Protein X X X �� no no 500 no no 311 noTRIGL Triglycerides X X X � � � n/a 5 5 600 86 86 373 n/aTRSF2 Transferrin ver.2 X X �� no no no no no no 1500T-UP3 T-Uptake X X �� n/a 33 33 1000 564 564 621UA2 Uric Acid ver.2 X X X � � �� 39 35 no 667 599 no noUIBC Unsaturated Iron-Binding Capacity X X �� no no 100 no no 62 200UREAL Urea/BUN X X X �� no no no no no no noVALP3 Valproic Acid X X � � �� n/a 38 38 1000 650 650 621VANC3 Vancomycin X X �� n/a 17 17 1000 291 291 621






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n/a = not applicableno = no significant interference up to the highest tested level� = over-recovery� = under-recovery�� = variable recovery�� = recovery within ±10 % of initial concentration1 Interferences were tested with the following substances added to samples:

Hemoglobin up to 621 µmol/l (1000 mg/dL)Bilirubin up to 1026 µmol/L (60 mg/dl)Lipemia up to 20 g/l Intralipid® (2000 mg/dl). Lipemia has no units as it is a measure of turbidity.Only significant interferences (>10%) are listed in the method sheetsReference: Glick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470–474.

2 L index not measured with Intralipid®, interference measured as Triglycerides (see Method Sheet)3 Endogenous bilirubin samples were used, total bilirubin was measured

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Reagents on cobas c 501 analyzer





~mg/dl ~mg/dl ~mg/dl ~µmol/l ~µmol/l~µmol/l Turbidity


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AAGP2 a1-Acid Glycoprotein Gen.2 X X X �� 650 1000 60 60 60 1000 1026 1026 621 650AAT2 a1-Antitrypsin ver.2 X X X �� 900 1000 60 60 60 1000 1026 1026 621 900ACETA Acetaminophen X X X4) �� 1200 150 25 25 25 150 428 428 93 1200ALB2 Albumin BCG Gen.2 X X X �� 550 1000 60 60 60 1000 1026 1026 621 550ALBS2 Albumin (Turbidimetric) X X X4) �� 1500 1000 60 60 60 1000 1026 1026 no 1500ALP2SALP2L ALP IFCC Gen.2 X X � �� 2000 200 35 35 60 200 599 1026 124 2000ALTL Alanine Aminotransferase X X X4) � � �� 150 200 60 60 60 200 1026 1026 124 150ALTLP Alanine Aminotransferase

Pyridoxal Phosphate Activated X X X4) � � �� 150 700 60 60 60 700 1026 1026 435 150AMYL2SAMY2 a-Amylase EPS ver.2 X X �� 1500 500 60 60 60 500 1026 1026 311 1500AMY-P a-Amylase EPS Pancreatic X X �� 1500 200 60 60 60 200 1026 1026 124 1500APOAT Apolipoprotein A-1 ver.2 X X X �� 1000 1000 60 60 60 1000 1026 1026 621 1000APOBT Apolipoprotein B ver.2 X X X �� 1000 1000 60 60 60 1000 1026 1026 621 1000ASLOT Antistreptolysin O X X8) X8) �� 1000 1000 60 60 60 1000 1026 1026 621 1000ASTLSASTL Aspartate Aminotransferase X X X4) �� 2) � 150 40 60 60 60 40 1026 1026 25 150ASTLP Aspartate Aminotransferase

Pyridoxal Phosphate Activated X X X4) �� 2) � 150 20 60 60 60 20 1026 1026 12 150AT Antithrombin X �� 1250 1000 60 60 60 1000 1026 1026 621 1250BIL-D Bilirubin Direct X X n/a n/a � 0 25 35 n/a n/a 35 n/a n/a 22 35D-BIL Bilirubin Direct (Multi) X n/a n/a � 0 10 100 n/a n/a 10 n/a n/a 6 100BILT2SBIL2 Bilirubin Total X X X4) n/a n/a � � 300 50 0 n/a n/a 50 n/a n/a 31 300BILTSSBILS Total Bilirubin Special X X X4) n/a n/a ��

6)�

7)600 500 0 n/a n/a 500 n/a n/a 311 600

C3C-2 Complement C3c ver.2 X X �� 2000 1000 60 60 60 1000 1026 1026 621 2000C4-2 Complement C4 ver.2 X X X �� 1000 500 60 60 60 500 1026 1026 311 1000CAS-CA Calcium X X �� 2000 1000 60 60 60 1000 1026 1026 621 2000CARB2 Carbamazepine X X X �� 2000 1000 50 50 50 1000 855 855 621 2000CERU Ceruloplasmin X X �� 200 1000 60 60 60 1000 1026 1026 621 200CHE2 Cholinesterase Gen.2 X X X4) �� 1000 700 60 60 60 700 1026 1026 435 1000CHED2 Cholinesterase/Dibucaine Gen.2 X X X4) �� 500 200 40 60 40 200 1026 684 124 500CHO2ICHO2A Cholesterol Gen.2 X X X4) � � � �� 2000 700 14 16 14 700 274 239 435 2000CKL Creatine Kinase X X �� 1000 200 60 60 60 200 1026 1026 124 1000CKMBL Creatine Kinase-MB X X � � � � 200 10 20 40 20 10 684 342 6 200CO2-LSCO2L Bicarbonate liquid X X �� 1800 400 60 60 60 400 1026 1026 248 1800CEEJ2 Creatinine Jaff‚ Gen.2 X X X � � � �� 800 1000 5 5 10 1000 86 171 621 800CREP2 Creatinine plus ver.2 X X X � � � � 2000 800 15 15 25 800 257 428 497 2000CRPHS C-Reactive Protein High Sensitive X X X4) �� 600 1000 60 60 60 1000 1026 1026 621 600CRPLX C-Reactive Protein X X X4) �� 400 500 60 60 60 500 1026 1026 311 400D-DI D-Dimer X X �� 750 500 20 20 20 500 342 342 311 750DIG Digoxin X X X4) �� 850 1000 60 60 60 1000 1026 1026 621 850DIGIT Digitoxin X X X4) �� 1000 1000 45 45 45 1000 770 770 621 1000ETOH2SETH2 Ethanol Gen.2 X X X4) � �� 500 200 30 30 60 200 513 1026 124 500FERR3 Ferritin Gen.3 X X X4) �� 500 400 60 60 60 400 1026 1026 248 500FRA Fructosamine X X X4) � � �� 1800 100 5 5 5 100 86 86 62 1800GENT2 Gentamicin X X X X �� 150 1000 50 50 50 1000 855 855 621 150

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~mg/dl ~mg/dl ~mg/dl ~µmol/l ~µmol/l~µmol/l Turbidity


(SI units):

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GGTI2GGTS2 γ-Glutamyltransferase ver.2 X X X4) �� 1500 200 20 50 20 200 855 342 124 1500GLUC2SGLU2 Glucose HK X X X4) X �� 1000 1000 60 60 60 1000 1026 1026 621 1000GLUC3SGLU3 Glucose HK Gen.3 X X X X �� 1000 1000 60 60 60 1000 1026 1026 621 1000HAPT2 Haptoglobin ver.2 X X X � �� 250 50 60 60 60 50 1026 1026 31 250HBDH2 HBDH Gen.2 X X X4) �� 600 10 60 60 60 10 1026 1026 6 600HDLC3 HDL-Cholesterol plus 3rd generation X X X4) � �� 1800 1200 30 30 60 1200 513 1026 745 1800IGA-2IGAP2 Immunoglobulin A X X X �� 2000 1000 60 60 60 1000 1026 1026 621 2000IGG-2 Immunoglobulin G X X X �� 2000 1000 60 60 60 1000 1026 1026 621 2000IGGC2 Immunoglobulin G X � �� n/a 0 0 0 15 15 200 257 257 124 n/aIGM-2 Immunoglobulin M X X X �� 2000 1000 60 60 60 1000 1026 1026 621 2000IGMP2 Immunoglobulin M X X X3) �� 1700 1000 60 60 60 1000 1026 1026 621 1700IRON2 Iron Gen.2 X X �� 1500 200 60 60 60 200 1026 1026 124 1500LACT2SLAC2 Lactate Gen.2 X � �� 1500 1000 28 28 60 1000 479 1026 621 1500LDHI2LDIP2 Lactate Dehydrogenase acc. IFCC ver.2 X X �� 1500 15 60 60 60 15 1026 1026 9 1500LDHL Lactate Dehydrogenase (P-L) X X �� 900 15 60 60 60 15 1026 1026 9 900LDL-C LDL-Cholesterol plus 2nd generation X X �� 200 1000 60 60 60 1000 1026 1026 621 200LI Lithium X X X4) �� 2000 1000 37 43 37 1000 735 633 621 2000LIPC Lipase colorimetric X X �� 2000 1000 60 60 60 1000 1026 1026 621 2000MGS-MG Magnesium X X �� 1700 1000 60 60 60 1000 1026 1026 621 1700MYO2 Myoglobin Gen.2 X X X4) �� 2000 400 60 60 60 400 1026 1026 248 2000NH3L Ammonia X4) � �� 50 200 10 10 30 200 171 513 124 505)PHNO3 CEDIA Phenobarbital X X X9) �� 1000 1000 60 60 60 1000 1026 1026 621 1000PHNY2 Phenytoin X X X �� 800 1000 50 50 50 1000 855 855 621 800PHOS2SPHO2 Phosphate (Inorganic) ver.2 X X X3) � �� 1250 300 40 40 60 300 684 1026 186 1250PREA Prealbumin X �� 200 1000 60 60 60 1000 1026 1026 621 200RF-II Rheumatoid Factors II X X X4) � �� 2000 300 40 40 60 300 684 1026 186 2000SALI Salicylate X X X4) �� 1000 1000 23 23 23 1000 393 393 621 1000STFR Soluble Transferrin Receptor X X X10) �� 1000 800 60 60 60 800 1026 1026 497 1000THEO2 Theophylline X X X �� 300 1000 50 50 50 1000 855 855 621 300TP2S-TP2 Total Protein X X X � � �� 2000 1000 20 20 20 1000 342 342 621 2000TRIGL Triglycerides X X X � � � n/a 0 700 10 10 35 700 171 599 435 n/aTRSF2 Transferrin ver.2 X X �� 500 1000 60 60 60 1000 1026 1026 621 500UA2 Uric Acid ver.2 X X X8) � � �� 1500 1000 40 40 40 1000 684 684 621 1500UIBC Unsaturated Iron-Binding Capacity X X8) � �� 300 40 60 60 60 40 1026 1026 25 300UREALSUREA Urea/BUN X X X �� 1000 1000 60 60 60 1000 1026 1026 621 1000VALP2 Valproic Acid X X X �� 500 500 30 30 30 500 513 513 311 500VANC2 Vancomycin X X X �� 500 650 30 30 30 650 513 513 404 500

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n/a = not applicableno = no significant interference up to the highest tested level� = over-recovery� = under-recovery�� = variable recovery�� = recovery within ±10 % of initial concentration1) Interferences were tested with the following substances added to samples: Hemoglobin up to 621 µmol/l (1000 mg/dL), Bilirubin up to 1026 µmol/L (60 mg/dl),

Lipemia up to 20 g/l Intralipid® (2000 mg/dl). Lipemia has no units as it is a measure of turbidity.Reference: Glick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470–474.

2) Erythrocytes contain AST3) Only K2-EDTA allowed, K3-EDTA is not allowed4) Only K2-EDTA has been checked5) Due to the fact that Intralipid contains NH3, the study performed with native lipemic samples6) Neonates7) Adults8) Plasma values are lower than serum values - Please refer to the pack insert9) Sodium EDTA10) Only K3-EDTA allowed, K2-EDTA is not suitable

Clinical chemistry analyzers

COBAS INTEGRA® Systems Designed to consolidate testing andincrease efficiency while reducing totalrunning costs of the laboratory.The broad reagent portfolio and theinnovative COBAS INTEGRA reagentcassette are combined with four provenmeasurement technologies and sophis-ticated, easy to use software.COBAS INTEGRA systems are the rightchoice for workflow consolidation inthe small to medium workload labora-tory and special chemistry testing inhigh volume sites. COBAS INTEGRA®800 allows the use of Roche/Hitachi 5-position sample racks for improvedpre-analytical sample flow.

Roche/Hitachi SystemsReliability, quality and convenience makethese analyzers the clinical chemistryworkhorse systems for routine test con-solidation. The broad reagent portfolioincludes more than 100 applications.The combination of throughput andautomation delivers high productivityfor the laboratory.

Immunochemistry analyzer

Elecsys® SystemsThe Elecsys systems family includes arange of immunochemistry analyzers,meeting automation requirements ofnearly all sizes of clinical laboratories.Dedicated STAT ports allow priorityhandling of emergency samples.The Elecsys systems family allows the useof Roche/Hitachi 5-position sample racksfor improved pre-analytical sample flow.

Serum Work Area solutions

MODULAR® ANALYTICS SWAcobas® 6000 analyzer series*Roche serum work area solutions offerone-touch sample processing with fullyautomated rack transport between theindividual modules. Rack traffic andsample throughput of the clinicalchemistry and immunoassay modulesare tailored to fulfil the turnaroundtime (TAT) requirements for routineand emergency samples.Reflex testing capabilities enable thelaboratory to apply indication orientedtesting cascades efficiently.

Consolidated Workstations

* cobas 6000 analyzer seriesis the first member of theRoche 2nd generation ofserum work area solutions.


[13] Thomas L. Hemolysis as influenceand interference factor.eJIFCC vol 13 no 4

[14] Kroll M. Evaluating InterferenceCaused by Lipemia.Editorial Clin Chem 2004; 11: 1968-1969

[15] Bornhorst J, Roberts R, Roberts W.Assay-Specific Differences inLipemic Interference in Native andIntralipid-Supplemented Samples.Clin Chem 2004; 11: 2197-2201

[16] Glick M, Ryder K, Glick S, WoodsJ. Unreliable Visual Estimation ofthe Incidence and Amount ofTurbidity, Hemolysis and Icterus inSerum from Hospitalized Patients.Clin Chem 1989; 35: 837-839

[17] Ryder K, Glick M, Glick S.Incidence and Amount ofTurbidity, Hemolysis and Icterus inSerum from Outpatients.Lab Med 1991; 22: 415-418

[18] Shingo S. Zero quality control:source inspection and the poka-yoke system. Cambridge, MA:Productivity Press, 1986; 1-60

[19] Hinckley C. Defining the best qual-ity-control systems by design andinspection.Clin Chem 1997; 43: 873-879

[20] Vermeer H, Thomassen E,de Jonge N.Clin Chem 2005; 1: 244-247

[21] Garber C, Witte D. Quality fortomorrow: by design or checking.Clin Chem 1997; 43: 864-865

[22] Glick M, Ryder K, Jackson S.Graphical Comparisons ofInterferences in Clinical ChemistryInstrumentation.Clin Chem 1986; 32: 470-475

[23] Jay D, Provasek D. Characterizationand Mathematical Correction ofHemolysis Interference in SelectedHitachi 717 Assays.Clin Chem 1993; 39: 1804-1810

[24] Pearson J. Serum Index IdentifiesLipemic Samples CausingInterference with Bilirubin Assay onHitachi 717. Clin Chem 1991; 37: 2014-2015

[25] Glick M, Ryder K, Jackson S.Graphical Comparisons ofInterferences in Clinical ChemistryInstrumentation. Clin Chem 1986;32: 470-475

References

[1] Plebani M, Carraro P. Mistakes in astat laboratory: types and frequency.Clin Chem 1997; 43: 1348-1351

[2] Ross J, Boone D. Assessing the effectof mistakes in the total testingprocess on the quality of patientcare (Abstract 102) In: Martin L,Wagner W, Essien JDK, eds 1989Institute of Critical Issues in HealthLaboratory Practice.Minneapolis, MN: DuPont Press, 1991

[3] Boone J, Steindel SD, Herron R,Howanitz PJ, Bachner P, Meier F,Schifman RB, Zarbo RJ.Transfusion medicine monitoringpractices.Arch Pathol Lab Med 1995; 119: 999-1006

[4] Lapworth R, Teal TK. Laboratoryblunders revisited.Ann Clin Biochem 1994; 31: 78-84

[5] Kalra J. Medical errors: impact onclinical laboratories and other criti-cal areas.Review Clin Biochem 2004; 37: 1052-1062

[6] Bonini P, Plebani M, Ceriotti F,Rubboli F. Errors in LaboratoryMedicine.Clin Chem 2002; 48: 691-698

[7] Chambers AM, Elder J, O’Reilly D.The blunder-rate in a clinical bio-chemistry service.Ann Clin Biochem 1986; 23: 470-473

[8] McSwiney RR, Woodrow DA. Typesof error within a clinical laboratory.J Med Lab Technol 1969; 26: 340-346

[9] Goldschmidt HMJ, Lent RW. Grosserrors and work flow analysis in theclinical laboratory.Klin Biochem Metab 1995; 3: 131-140

[10] Kroll M, Elin, R. Interference withClinical laboratory Analyzes Clin Chem 1994; 40: 1996-2005

[11] Guder W, da Fonseca-Wollheim F,Heil W, Schmitt Y, Toepfer G,Goerlitz H, Zawta B. TheHemolytic, Icteric and LipemicSample RecommendationsRegarding their Recognition andPrevention of Clinically RelevantInterferences.J Lab Med 2000; 24: 357-364

[12] Grafmeyer D, Bondon M,Manchon M, Levillain P. TheInfluence of Bilirubin, Hemolysisand Turbidity on 20 AnalyticalTests Performed on AutomaticAnalyzers.Eur J Clin Chem Clin Biochem1995; 33: 31-52


Notes


Documents

Serum Indices: Reduction of clinical errors in laboratory medicine