AU US CRP LATEX

Instructions For Use CRP Latex

© 2018 Beckman Coulter, Inc. All rights reserved.
OSR6199 4 x 30 mL R1, 4 x 30 mL R2

For in vitro diagnostic use only.

For Rx use only

ANNUAL REVIEW
Reviewed by Date Reviewed by Date

PRINCIPLE
INTENDED USE

System reagent for the quantitative determination of C-Reactive Protein in human serum and plasma on Beckman Coulter
AU Analyzers. Measurement of CRP is useful for the detection and evaluation of infection, tissue injury, inflammatory
disorders and associated diseases. Measurements may also be useful as an aid in the identification of individuals at risk
for future cardiovascular disease. High sensitivity CRP (hsCRP) measurements, when used in conjunction with traditional
clinical laboratory evaluation of acute coronary syndromes, may be useful as an independent marker of prognosis for
recurrent events, in patients with stable coronary disease or acute coronary syndromes.1,2

SUMMARY AND EXPLANATION

C-reactive protein (CRP) is one of the most sensitive acute-phase reactants. With the Beckman Coulter AU System CRP
Latex reagent, CRP can be measured down to very low concentrations. Depending on the application used (different
instrument settings) two measuring ranges are available:
1. Normal Application (1.0 - 480 mg/L): C-reactive protein levels in serum can rise dramatically after myocardial
infarction, stress, trauma, infection, inflammation, surgery, or neoplastic proliferation. The increase occurs within
24 to 48 hours, and the level may be 2000 times normal. Because the increase is non-specific, however, it cannot
be interpreted without a complete clinical history, and even then only by comparison with previous values.
2. Highly Sensitive (Cardiac / Neonatal) Application
AU400/400e/480, AU640/640e/680 (0.2 - 160 mg/L).
AU2700/5400/5800/DxC 700 AU (0.2 - 80 mg/L).
Studies have also shown that the detection of much lower CRP levels can provide valuable information. The
typical CRP concentration for healthy adults is (depending on the specific level of the individual patient) < 1 mg/L.3
Slightly higher values can indicate an increased risk for coronary heart disease in asymptomatic patients.1,2 CRP

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 concentrations above 3 mg/L, at the time of hospital admission, predict a precarious outcome after a myocardial
infarct.4 The following relative risk categories in relation to average CRP level have been recommended5: Low <
1mg/L, Average 1.0 to 3.0 mg/L and High > 3.0 mg/L.
Increases in C-Reactive Protein values are not specific and should not be interpreted without a complete clinical
history since CRP is an acute phase protein which can rise non-specifically due to other inflammatory conditions.
For cardiac risk analysis, other cardiac disease-specific testing must be done, such as Total cholesterol, HDL
cholesterol, and LDL cholesterol. When being used for risk assessment, levels of CRP > 10 mg/L should be
evaluated for other non-cardiovascular origins. Testing for any risk assessment should not be performed while
there is indication of infection, systemic inflammation, or trauma. This assay is not meant for management of acute
coronary syndrome and is not a substitute for traditional cardiovascular risk factors. Screening the entire adult
population for hsCRP is not recommended. The average of hsCRP levels determined two weeks apart should be
used in performing risk assessment on metabolically stable patients. hsCRP is considered to be a Class IIa marker
for acute coronary syndrome in addition to Troponin I.6
Cord blood normally has very low CRP concentrations (median 0.12 mg/L7). In the diagnostic evaluation of neonates
with suspected infection, measurements of serial CRP levels are useful. Two low CRP levels obtained 24 hours apart
indicate that bacterial infection is highly unlikely.8 Thus, CRP Latex reagent is a valuable tool for the early diagnosis of
infection in preterm infants and neonates. It assesses both the need for, and the effectiveness of, antibiotic treatment.
However, CRP values alone should not be used as a basis for early discontinuance of antibiotic therapy.

METHODOLOGY

Immune complexes formed in solution scatter light in proportion to their size, shape, and concentration. Turbidimeters
measure the reduction of incidence light due to reflection, absorption or scatter. In this procedure, the measurement
of the rate of decrease in light intensity transmitted (increase in absorbance) through particles suspended in solution
is the result of complexes formed during the immunological reaction between the CRP of the patient serum and rabbit
anti-CRP-antibodies coated on latex particles.

SPECIMEN
SPECIMEN STORAGE AND STABILITY

C-reactive protein specimens are stable for 11 days at 20 - 25°C and 2 months at 4 - 8°C in serum and plasma. For
longer storage, freeze serum to -20°C.9
Specimen storage and stability information provides guidance to the laboratory. Based on specific needs, each laboratory
may establish alternative storage and stability information according to good laboratory practice or from alternative
reference documentation.
Additional handling conditions as designated by this laboratory:

SPECIMEN COLLECTION AND PREPARATION

Serum, EDTA and Lithium heparin plasma may be used.

Comparison studies have shown no statistical significant difference between CRP recovery in serum and plasma within
the accuracy and precision limits of the assay.
Centrifuge samples containing precipitates before performing the assay.

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Additional instructions for patient sample preparation as designated by this laboratory:

Additional type conditions as designated by this laboratory:

REAGENTS
CONTENTS

CRP Latex Reagent

Reagent storage location in this laboratory:

WARNING AND PRECAUTIONS

1. Exercise the normal precautions required for handling all laboratory reagents.
2. Dispose of all waste material in accordance with local guidelines.
3. This product contains material of animal origin. The product should be considered as potentially capable of
transmitting infectious diseases.

REACTIVE INGREDIENTS

Final concentration of reactive ingredients:

Glycine buffer 100 mmol/L

Latex coated with anti-CRP Antibodies < 0.5%
Also contains preservatives.

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 CAUTION
Sodium azide preservative may form explosive compounds in metal drain lines.
See NIOSH Bulletin: Explosive Azide Hazard (8/16/76).
To avoid the possible build-up of azide compounds, flush wastepipes with
water after the disposal of undiluted reagent. Sodium azide disposal must be in
accordance with appropriate local regulations.

GHS HAZARD CLASSIFICATION

Not classified as hazardous

Safety Data Sheet is available at techdocs.beckmancoulter.com

MATERIALS NEEDED BUT NOT SUPPLIED WITH REAGENT KIT

CRP Latex Calibrator Normal (N) Set (Cat # ODC0026) for the Normal Application.
CRP Latex Calibrator Highly Sensitive (HS) Set (Cat # ODC0027) for the Highly Sensitive Application.
0.9% Saline
Storage location of the Calibrator in this laboratory:

EQUIPMENT AND MATERIALS

For AU400/400e/480, AU640/640e/680, AU2700/5400/AU5800 and DxC 700 AU Beckman Coulter Analyzers.
Storage location of test tubes or sample cups in this laboratory:

REAGENT PREPARATION

The CRP Latex reagents are ready for use. No preparation is required. Agitate gently before use to ensure a uniform
suspension of particles. Repeat at weekly intervals thereafter.

REAGENT STORAGE AND STABILITY

1. The unopened reagents are stable until the expiration date printed on the label when stored at 2 - 8°C.
2. Opened bottles of reagent are stable for 90 days when stored in the refrigerated compartment of the analyzer.

INDICATIONS OF DETERIORATION

Gross turbidity or precipitate in R1, or visible signs of microbial growth in the C-Reactive Protein reagents may indicate
degradation and warrant discontinuation of use.

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Additional storage requirements as designated by this laboratory:

STABILITY OF FINAL REACTION MIXTURE

The Beckman Coulter AU analyzer automatically computes every determination at the same time interval.

CALIBRATION
CALIBRATION INFORMATION

The frequency of calibration for the CRP Latex procedure is every 90 days for the Normal and Highly Sensitive
Applications. Calibration of this CRP Latex procedure is traceable to IFCC (International Federation of Clinical
Chemistry) standard CRM 470 (RPPHS).
6 levels are required to calibrate both the CRP Latex Normal and CRP Highly Sensitive applications. Levels 2 to 6 are
provided in the calibrator kits. For the Level 1 calibrator 0.9% saline should be used.
Recalibration of this test is required when any of these conditions exist:
1. A reagent lot number has changed or there is an observed shift in control values.
2. Major preventative maintenance was performed on the analyzer.
3. A critical part was replaced.

QUALITY CONTROL
During operation of the Beckman Coulter AU analyzer, at least two levels of an appropriate quality control material
should be tested a minimum of once a day. In addition, controls should be performed after calibration with each new
lot of reagent, and after specific maintenance or troubleshooting steps described in the appropriate Beckman Coulter
AU analyzer User Guide/Instructions For Use (IFU). Quality control testing should be performed in accordance with
regulatory requirements and each laboratory’s standard procedure.
Please note that recovery of non-Beckman Coulter controls may vary with reagent lots of immunoassay products, due
to the use of non-human materials in the controls.
Location of controls used at this laboratory.

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 CONTROL NAME SAMPLE TYPE STORAGE

TESTING PROCEDURE(S)
A complete list of test parameters and operational procedure can be found in the User Guide/IFU appropriate to the
Beckman Coulter AU analyzer.

RESULTS INTERPRETATION
Automatically printed out for each sample in mg/L at 37°C.

REPORTING RESULTS
EXPECTED RESULTS

C-Reactive Protein is a non-specific indicator for a wide range of disease processes. Reference intervals may be affected
by different factors.

Normal Application
10 – 50 mg/L indicates mild inflammation, 50-100 mg/L indicates more severe inflammation and >100 mg/L represents
serious processes and frequently indicates the presence of a bacterial infection10.

Highly Sensitive Application

Recommended Cardiac risk assessment categories:

Low < 1 mg/L

Average 1.0 to 3.0 mg/L
High >3.0 mg/L
Newborns with no evidence of infection have CRP concentrations of <10 mg/L.11
Because of the variation depending on age, sex, diet, and geographical location, each laboratory should determine its
own expected values for the different patient groups as dictated by good laboratory practice.

Expected reference ranges in this laboratory:

INTERVALS SAMPLE TYPE UNITS

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Additional reporting information as designated by this laboratory:

PROCEDURAL NOTES
ANTICOAGULANT TEST RESULTS
The following anticoagulants were assessed by Deming regression analysis with a minimum of 40 paired serum and
plasma samples. Values of serum (X) ranging from 1.16 mg/L to 436.47 mg/L for normal application and 0.34mg/L to
73.11 mg/L for highly sensitive application were compared with the values for plasma (Y) yielding the following results.

Application Normal Application Highly Sensitive Application

Y Method EDTA Lithium Heparin EDTA Lithium Heparin
X Method SERUM SERUM SERUM SERUM
Slope 0.998 1.003 0.990 0.985
Intercept -0.0.54 -0.015 -0.059 -0.013
Y= 0.998x - 0.054 1.003x - 0.015 0.990x - 0.059 0.985x - 0.013
Correlation Coeff.(r) 1.000 1.000 0.999 1.000

INTERFERENCES

Normal and Highly Sensitive Applications

Results of studies12 show that the following substances may interfere with this C-reactive protein procedure.13
Inaccuracies due to bilirubin (40 mg/dL) are less than 5% at CRP concentrations of 1 mg/L
Inaccuracies due to hemolysate (500 mg/dL) are less than 5% at CRP concentrations of 1 mg/L
Inaccuracies due to intralipid* (1,000 mg/dL) are less than 10% at CRP concentrations of 1 mg/L
* Intralipid, manufactured by Pharmacia, is a 20% fat emulsion used to emulate extremely turbid samples.
In very rare cases gammopathy, especially monoclonal IgM (Waldenström’s macroglobulinemia), may cause unreliable
results.
Samples containing heterophilic antibodies can cause falsely elevated results. Please note that oral contraceptives have
been reported to affect results.14
The information presented is based on results from Beckman Coulter studies. Beckman Coulter Inc. makes no
representation about the completeness or accuracy of results generated by future studies. For further information on
interfering substances, refer to Young15 for a compilation of reported interferences.
Laboratory specific procedure notes:

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PERFORMANCE CHARACTERISTICS
PERFORMANCE CHARACTERISTICS

The following data was obtained using the CRP Latex reagent on Beckman Coulter AU analyzers according to
established procedures. Results obtained in individual laboratories may differ.

DYNAMIC RANGE / ANALYTICAL MEASURING RANGE

The CRP Latex reagent is linear from:

Assay Range Highly Sensitive

Beckman Coulter AU Analyzers Assay Range Normal Application Application
AU400/400e/480 1.0 to 480 mg/L 0.2 to 160 mg/L
AU640/640e/680 1.0 to 480 mg/L 0.2 to 160 mg/L
AU2700/5400/5800/DxC 700 AU 1.0 to 480 mg/L 0.2 to 80 mg/L

Normal Application
Samples that are above the linear range of the normal application may be manually diluted 1 in 2 using physiological
saline, repeated, and multiplied by the dilution factor.
Samples measuring below the measuring range for the normal CRP application should be reported as < 1.0 mg/L.

Highly Sensitive Application

Samples that are above the linear range of the highly sensitive application may be re-run using the normal application
or manually diluted 1 in 2 using physiological saline, repeated, and multiplied by the dilution factor.
Samples measuring below the measuring range for the Highly Sensitive CRP application should be reported as < 0.2
mg/L.

LIMITATIONS
1. Sample carryover may occur when a high CRP sample >160mg/L is run directly before a sample with low CRP.
Sample contamination avoidance parameters should be programmed on the AU2700/5400/5800/480/680 and DxC
700 AU instruments and are available on the Beckman Coulter website.
On the AU400/400e and AU640/640e measures should be taken to repeat samples < 2.0 mg/L that follow CRP
results > 160mg/L.
2. Prozone
Normal Application
Patients with inflammatory and/or infectious conditions should have their CRP measured using the Normal
Application, particularly when used for patient monitoring. When using the Normal Application on all Beckman
Coulter AU systems, patients with CRP concentrations up to 750 mg/L will not generate false low results within
the analytical range.
Highly Sensitive Application
When using the Highly Sensitive Application on the Beckman Coulter AU400/400e/480/640/640e/680 systems,
patients with CRP concentrations up to 400 mg/L will not generate false low results within the analytical range.
When using the Highly Sensitive Application on the Beckman Coulter AU2700/5400/5800/DxC 700 AU systems,
patients with CRP concentrations up to 750 mg/L will not generate false low results within the analytical range.

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 3. The Highly Sensitive application is intended for use in the monitoring of neonates. Basal levels of CRP in neonates
are very low. This assay protocol was specifically designed for optimal performance at these levels.
4. Increases in the C-Reactive Protein values are not specific and should not be interpreted without a complete clinical
history. When used for cardiovascular risk assessment, these measurements should be compared to previous
C-Reactive Protein values.

SENSITIVITY

Limit of Detection / Limit of Quantitation

The Limit of Detection (LoD) and Limit of Quantitation (LoQ) were determined in accordance with the CLSI EP17-A
guideline16 on the AU5800 & DxC 700 AU analyzers.
Correctly operating AU Systems should exhibit sensitivity less than or equal to 1.0 mg/L for the Normal Application and
less than or equal to 0.2 mg/L for the Highly Sensitive Application.
The following data was obtained on a DxC 700 AU analyzer:

Application LoD LoQ

Normal 0.23 mg/L 0.52 mg/L
Highly Sensitive 0.08 mg/L 0.08 mg/L

Lower Limit of Detection / Functional Sensitivity

The Lower Limit of Detection (LLD) and Functional Sensitivity were determined on the AU400/400e/640/640e/2700/5400
analyzers.
The LLD was calculated as mean recovery +3 SD of a 20-fold determination of an analyte-free sample. Normal
application: ≤ 0.15 mg/L, Highly Sensitive application: ≤ 0.07 mg/L.
The Functional Sensitivity is the lowest CRP level the assay can measure accurately with a CV of < 20% (25-fold
determination). Normal application: ≤ 1.0 mg/L, Highly Sensitive application: ≤ 0.2 mg/L.

METHODS COMPARISON

Patient samples were used to compare this CRP Latex Reagent. The table below demonstrates representative
performance on AU analyzers.17

Normal application
Y Method DxC 700 AU
X Method AU5800
Slope 0.987
Intercept -0.111
Correlation Coeff. (r) 1.000
No. of Samples (n) 117
Range (mg/L) 1.24 - 273.33

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 Highly Sensitive Application
Y Method DxC 700 AU
X Method AU5800
Slope 1.013
Intercept -0.050
Correlation Coeff. (r) 1.000
No. of Samples (n) 117
Range (mg/L) 0.27 - 70.50

PRECISION

Estimates of precision, based on CLSI recommendations,18 are consistent with typical performance.17

Application Within-Run Precision Total Precision

Normal Application ≤5% CV or SD ≤0.20 mg/L ≤10% CV or SD ≤0.25 mg/L
Highly Sensitive Application SD ≤ 0.02 mg/L SD ≤ 0.02 mg/L
Assays of serum pools and control sera were performed and the data reduced following the CLSI guidelines above.
The following data was generated on a representative AU analyzer:

Normal Application – AU640

N= 80 Within-run Total
Mean, mg/L SD CV% SD CV%
6.56 0.07 1.09 0.12 1.85
64.79 0.78 1.20 2.16 3.34
137.71 0.96 0.70 2.26 1.64

Highly Sensitive Application – AU640

N= 80 Within-run Total
Mean, mg/L SD CV% SD CV%
0.21 0.01 4.08 0.01 4.87
1.05 0.03 2.96 0.03 2.50
2.99 0.02 0.62 0.03 0.92
10.00 0.09 0.95 0.15 1.53
59.38 0.54 0.91 1.00 1.68
146.95 1.12 0.76 2.34 1.59

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ADDITIONAL INFORMATION
DxC 700 AU requires that each reagent application has a standard format of abbreviated Closed Test Name. This Closed
Test Name is required to allow automated loading of the calibrator information for each application as part of the DxC
700 AU Closed System. Refer to the table below for the Closed Test Name assigned to each application for this assay.

Test Name Description

CRP1U CRP Latex (Serum)
CRP2U CRP Latex (Serum)

Setting Sheet Footnotes

# User defined
## Lot + Bottle
§ Saline should be used for the Level 1 calibrator.
† Beckman Coulter CRP Latex Calibrator Normal Set Cat No.: ODC0026
† Beckman Coulter CRP Latex Calibrator Highly Sensitive Set Cat No.: ODC0027
* Values set for working in mg/L. To work in mg/dL divide by 10

REVISION HISTORY

Revised Specimen
Updated Warning and Precautions section

Preceding version revision history

Added new Brazilian address
There is no change to the IFU content

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REFERENCES
1. Morrow, A.D., Ridker, P.M. C-reactive protein, inflammation, and coronary risk Med. Clin. of North Am. 2000; 84:
149161.

2. Ridker, P.M. Novel risk factors and markers for coronary disease. Adv. Int. Med.2000; 45: 391-419.

3. Raifai N, Ridker PM. Population Distributions of C-reactive Protein in Apparently Healthy Men and Women in the
United States: Implication for Clinical Interpretation. Clin Chem 2003;49:666-669.

4. Ridker, P.M., Cannon, C. P., Morrow, D., Rifai, N., Rose, L. M., McCabe, C. H., Pfeffer, M. A., Braunwald, E.,
C-Reactive Protein Levels and Outcomes after Statin Therapy. N. Eng. J. Med. 2005, 352, 20-28.

5. Pearson TA et al. Markers of inflammation and cardiovascular disease. Application to clinical and public health
practice. A statement for healthcare professionals from the Centers for Disease Control and Prevention and the
American Heart Association. http://www.circulationaha.org.

6. NACB "Biomarkers of Acute Coronary Syndrome & Heart Failure" (draft guidelines) R.H. Christianson, et al AACC
Press, 2004.

7. Wasunna A., Whitelaw A., Gallimore R., Hawkins P.N., Pepys M.B. C-reactive protein and bacterial infection in
preterm infants. Eur.J. Pediatr. 1990; 149: 424-7.

8. Benitz, W.E., Han, M.Y., Madan, A. Ramachandra, P. Serial serum C-reactive protein levels in the diagnosis of
neonatal infection. Neonatals1998; 102: 4.

9. WHO/DIL/LAB/99.1 Rev.2 World Health Organization. Use of Anticoagulants in Diagnostic Laboratory

Investigations 2002.

10. Thomas, L., Clinical Laboratory Diagnostics Use and Assessment of Clinical Laboratory Result, 1st Edition,
TH-Books Verlagsgesellschaft, Frankfurt, Germany,1998.

11. Claudio Chiesa et al., C reactive protein and procalcitonin: Reference intervals for preterm and term newborns
during the early neonatal period, Clinica Chimica Acta, Volume 412, 12 May 2011, Pages 1053-1059.

12. CLSI/NCCLS, Interference Testing in Clinical Chemistry, EP7-A, 2002.

13. In-house data available upon request.

14. Ashwood, E.R., Burtis, C.A., Tietz Textbook of Clinical Chemistry, 2nd Edition, W.B. Saunders, 1994.

15. Young, D.S., Effects of Drugs on Clinical Laboratory Tests, 5th Edition, AACC Press, 2000.

16. CLSI, protocol for determination of limit of detection and limit of quantitation;Approved guidline, EP17-A, 2004

17. Data is on file for specific AU analyzers.

18. CLSI/NCCLS Evaluation of Precision Performance of Quantitative Measurement Methods, EP5-A2, 2004.

Beckman Coulter, Inc., 250 S. Kraemer Blvd., Brea, CA 92821 U.S.A.

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