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If you require further information please refer to the full Method Sheet PDF under the given link, or contact your local Roche country representative." }, "Chapters": [ { "Name": "IntendedUse", "Value": "

Intended use

In vitro test for the quantitative determination of the catalytic activity of creatine kinase MB subunit (CK‑MB) in human serum and plasma oncobas c systems.

", "Language": "en" }, { "Name": "TestPrinciple", "Value": "

Test principle

Immunological UV assay

  • Sample and addition of R1 (buffer/enzymes/coenzyme)

  • Addition of R2 (buffer/substrate/antibody) and start of reaction.

Human CK‑MB is composed of two subunits, CK‑M and CK‑B which both have an active site. With the aid of specific antibodies to CK‑M, the catalytic activity of CK‑M subunits in the sample is inhibited to 99.6 % without affecting the CK‑B subunits. The remaining CK‑B activity, corresponding to half the CK‑MB activity, is determined by the total CK method. As the CK‑BB isoenzyme only rarely appears in serum and the catalytic activity of the CK‑M and CK‑B subunits hardly differ, the catalytic activity of the CK‑MB isoenzyme can be calculated from the measured CK‑B activity by multiplying the result by 2.

", "Language": "en" }, { "Name": "MeasuringRange", "Value": "

Limits and ranges

Measuring range

3‑2000 U/L (0.05‑33.4 µkat/L)

Determine samples having higher activities via the rerun function. Dilution of samples via the rerun function is a 1:3 dilution. Results from samples diluted by the rerun function are automatically multiplied by a factor of 3.

Lower limits of measurement

Limit of Blank, Limit of Detection and Limit of Quantitation

Limit of Blank

= 3 U/L (0.05 µkat/L)

Limit of Detection

= 3 U/L (0.05 µkat/L)

Limit of Quantitation

= 5 U/L (0.08 µkat/L)

The Limit of Blank, Limit of Detection and Limit of Quantitation were determined in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP17‑A2 requirements.

The Limit of Blank is the 95th percentile value from n ≥ 60 measurements of analyte‑free samples over several independent series. The Limit of Blank corresponds to the activity below which analyte‑free samples are found with a probability of 95 %.

The Limit of Detection is determined based on the Limit of Blank and the standard deviation of low activity samples.

The Limit of Detection corresponds to the lowest analyte activity which can be detected (value above the Limit of Blank with a probability of 95 %).

The Limit of Quantitation is the lowest analyte activity that can be reproducibly measured with a total error of 20 %. It has been determined using low activity CK‑MB samples.

", "Language": "en" }, { "Name": "ExpectedValues", "Value": "

Expected values

Reference intervals strongly depend on the patient group regarded and the specific clinical situation.

U/L

For healthy people: Reference range (37 °C) according to Klein et al.
LREFKlein G, Berger A, Bertholf R, et al. Abstract: Multicenter Evaluation of Liquid Reagents for CK, CK-MB and LDH with Determination of Reference Intervals on Hitachi Systems. Clin Chem 2001;47:Suppl. A30.
and consensus values:
LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308.

< 25 U/L

For myocardial infarction diagnosis using the combination CK and CK‑MB (activity), and representing a CK consensus value based on long‑term experience:
LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308.
,
LREFStein W. Strategie der klinischen-chemischen Diagnostik des frischen Myokardinfarktes. Med Welt 1985;36:572-577.

1.

CKmen

> 190 U/L

CKwomen

> 167 U/L

2.

CK‑MB

> 24 U/L

3.

The CK‑MB activity accounts for 6‑25 % of the total CK activity.

µkat/L

For healthy people: Reference range (37 °C) according to Klein et al.
LREFKlein G, Berger A, Bertholf R, et al. Abstract: Multicenter Evaluation of Liquid Reagents for CK, CK-MB and LDH with Determination of Reference Intervals on Hitachi Systems. Clin Chem 2001;47:Suppl. A30.
and consensus values:
LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308.
*

< 0.418 µkat/L

*calculated by unit conversion factor

For myocardial infarction diagnosis using the combination CK and CK‑MB (activity), and representing a CK consensus value based on long‑term experience:
LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308.
,
LREFStein W. Strategie der klinischen-chemischen Diagnostik des frischen Myokardinfarktes. Med Welt 1985;36:572-577.

1.

CKmen

> 3.17 µkat/L

CKwomen

> 2.79 µkat/L

2.

CK‑MB

> 0.40 µkat/L

3.

The CK‑MB activity accounts for 6‑25 % of the total CK activity.

When myocardial infarction is suspected the diagnostic strategy proposals in the consensus document of European and American cardiologists should in general be followed.

LREFMyocardial Infarction Redefined - A Consensus Document of the Joint European Society of Cardiology/ American College of Cardiology Committee for the Redefinition of Myocardial Infarction. Eur Heart J 2000;21:1502-1513.

If despite the suspicion of myocardial infarction the values found remain below the stated limits, a fresh infarction may be involved. In such cases the determinations should be repeated after 4 hours.

Maximum diagnostic efficiency of the CK‑MB determination will be obtained when a sequential sampling protocol is used and consideration is given to the time pattern of activity over a 6 to 48 hour period. When only CK‑MB activity is used, the diagnostic efficiency will be lower and will vary with the sampling time.

LREFMoss DW, Henderson AR, Kachmar JF. Enzymes. In: Tietz NW, ed. Fundamentals of Clinical Chemistry, 3rd ed. Philadelphia, PA: WB Saunders 1987;346-421.
,
LREFRemaley AT, Wilding P. Macroenzymes: Biochemical Characterization, Clinical Significance, and Laboratory Detection. Clin Chem 1989;35:2261-2270.

Each laboratory should investigate the transferability of the expected values to its own patient population and if necessary determine its own reference ranges.

", "Language": "en" }, { "Name": "LimitationInterference", "Value": "

Limitations - interference

The total CK activity of the specimen should be determined prior to performing the CK-MB assay. The amount of anti‑human CK‑M subunit antibody in the CK-MB reagent is sufficient for the complete inhibition of up to 4000 U/L CK‑M activity. If the total CK activity exceeds 4000 U/L, the specimen requires dilution because complete inhibition of the CK‑M subunit is no longer assured. In patients with a disposition to macro‑CK formation, implausibly high CK‑MB values may be measured in relation to the total CK, since the macroforms mainly consist of CK‑B subunits. As these patients have generally not suffered a myocardial infarction, additional diagnostic measures are necessary.

LREFRemaley AT, Wilding P. Macroenzymes: Biochemical Characterization, Clinical Significance, and Laboratory Detection. Clin Chem 1989;35:2261-2270.

Criterion: Recovery within ± 10 % of initial value at a CK‑MB activity of ≥ 25 U/L.

Icterus:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an I index of 60 for conjugated and 20 for unconjugated bilirubin (approximate conjugated bilirubin concentration: 1026 µmol/L or 60 mg/dL and approximate unconjugated bilirubin concentration: 342 µmol/L or 20 mg/dL).

Hemolysis:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an H index of 20 (approximate hemoglobin concentration: 12.4 µmol/L or 20 mg/dL).

Lipemia (Intralipid):

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an L index of 500. There is poor correlation between the L index (corresponds to turbidity) and triglycerides concentration.

Adenylate kinase: Adenylate kinase (AK) may cause positive interference. Sources of AK in the blood are erythrocytes, muscle, and liver. In order to reduce AK interference to a minimum, AMP and Ap5A are included in the reagent. The AMP/Ap5A mixture causes 97 % inhibition of the AK from erythrocytes and muscle, and 95 % inhibition of the AK from liver.

LREFBergmeyer HU, Breuer H, Büttner H, et al. Empfehlungen der Deutschen Gesellschaft für Klinische Chemie. Standard-Methode zur Bestimmung der Aktivität der Creatin-Kinase. J Clin Chem Clin Biochem 1977;15:249-254.
The slight residual AK activity does not influence the assay of total CK, but may affect the low CK‑MB activities.

Drugs: No interference was found at therapeutic concentrations using common drug panels.

LREFBreuer J. Report on the Symposium "Drug effects in Clinical Chemistry Methods". Eur J Clin Chem Clin Biochem 1996;34:385-386.
,
LREFSonntag O, Scholer A. Drug interference in clinical chemistry: recommendation of drugs and their concentrations to be used in drug interference studies. Ann Clin Biochem 2001;38:376-385.
Exceptions: Cyanokit (hydroxocobalamin) and cefoxitin at therapeutic concentrations interfere with the test.

In very rare cases, gammopathy, in particular type IgM (Waldenström’s macroglobulinemia), may cause unreliable results.

LREFBakker AJ, Mücke M. Gammopathy interference in clinical chemistry assays: mechanisms, detection and prevention. Clin Chem Lab Med 2007;45(9):1240-1243.

For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.

ACTION REQUIRED
Special Wash Programming: The use of special wash steps is mandatory when certain test combinations are run together on cobas c systems. All special wash programming necessary for avoiding carry-over is available via the cobas link. The latest version of the carry-over evasion list can be found with the NaOHD/SMS/SCCS Method Sheet. For further instructions, refer to the operator’s manual.

", "Language": "en" }, { "Name": "OrderInformation", "Value": "

OrderInformation (CC Reagents - cobas + Integra)

Order information

Analyzer(s) on which cobas c pack(s) can be used

08057486190

Creatine Kinase‑MB (150 tests)

System‑ID 2043 001

cobas c 303, cobas c 503

Materials required (but not provided):

11447394216

Calibrator f.a.s. CK‑MB (3 x 1 mL)

Code 20402

05117003190

PreciControl ClinChem Multi 1 (20 x 5 mL)

Code 20391

05947626190

PreciControl ClinChem Multi 1 (4 x 5 mL)

Code 20391

05117216190

PreciControl ClinChem Multi 2 (20 x 5 mL)

Code 20392

05947774190

PreciControl ClinChem Multi 2 (4 x 5 mL)

Code 20392

08063494190

Diluent NaCl 9 % (123 mL)

System-ID 2906 001

", "Language": "en" }, { "Name": "SystemInformation", "Value": "

System information

CKMB2: ACN 20430

", "Language": "en" }, { "Name": "Handling", "Value": "

Reagent handling

Ready for use

", "Language": "en" }, { "Name": "TestDefinition", "Value": "

Application for serum and plasma

Test definition

Reporting time

10 min

Wavelength (sub/main)

546/340 nm

Reagent pipetting

Diluent (H2O)

R1

79 µL

R2

16 µL

Sample volumes

Sample

Sample dilution

Sample

Diluent (NaCl)

Normal

3.9 µL

Decreased

11.7 µL

10 µL

80 µL

Increased

3.9 µL

For further information about the assay test definitions refer to the application parameters setting screen of the corresponding analyzer and assay.

", "Language": "en" }, { "Name": "StorageStability", "Value": "

Storage and stability

Shelf life at 2‑8 °C:

See expiration date on cobas c pack label.

On‑board in use and refrigerated on the analyzer:

8 weeks

", "Language": "en" }, { "Name": "Calibration", "Value": "

Calibration

Calibrators

S1: H2O

S2: C.f.a.s. CK‑MB

Calibration mode

Linear

Calibration frequency

Automatic full calibration
- after reagent lot change

Full calibration
- as required following quality control procedures

Calibration interval may be extended based on acceptable verification of calibration by the laboratory.

Traceability: This method has been standardized against the IFCC Method for Creatine Kinase

LREFSchumann G, Bonora R, Ceriotti F, et al. IFCC Primary Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes at 37 °C – Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase. Clin Chem Lab Med 2002;40(6):635-642.
with addition of antibodies.

", "Language": "en" }, { "Name": "Limitations", "Value": "", "Language": "en" }, { "Name": "PerformanceData", "Value": "

Specific performance data

Representative performance data on the analyzers are given below. These data represent the performance of the analytical procedure itself.

Results obtained in individual laboratories may differ due to heterogenous sample materials, aging of analyzer components and mixture of reagents running on the analyzer.

", "Language": "en" }, { "Name": "Precision", "Value": "

Precision

Precision was determined using human samples and controls in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP05-A3 requirements with repeatability (n = 84) and intermediate precision (2 aliquots per run, 2 runs per day, 21 days). Results for repeatability and intermediate precision were obtained on the cobas c 503 analyzer.

Repeatability

Mean
U/L

SD
U/L

CV
%

PCCC1a)

42.9

0.380

0.9

PCCC2b)

96.9

0.365

0.4

Human serum 1

16.0

0.358

2.2

Human serum 2

22.6

0.365

1.6

Human serum 3

190

0.779

0.4

Human serum 4

997

2.61

0.3

Human serum 5

1782

4.80

0.3

Intermediate precision

Mean
U/L

SD
U/L

CV
%

PCCC1

FREFPreciControl ClinChem Multi 1

42.9

0.557

1.3

PCCC2

FREFPreciControl ClinChem Multi 2

96.6

0.712

0.7

Human serum 1

15.5

0.507

3.3

Human serum 2

22.3

0.560

2.5

Human serum 3

190

3.24

1.7

Human serum 4

997

11.1

1.1

Human serum 5

1784

28.1

1.6

The data obtained on cobas c 503 analyzer(s) are representative for cobas c 303 analyzer(s).

", "Language": "en" }, { "Name": "MethodComparison", "Value": "

Method comparison

CK‑MB values for human serum and plasma samples obtained on a cobas c 503 analyzer (y) were compared with those determined using the corresponding reagent on a cobas c 501 analyzer (x).

Sample size (n) = 69

Passing/Bablok

LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790.

Linear regression

y = 1.014x − 1.73 U/L

y = 1.013x − 1.24 U/L

τ = 0.964

r = 1.000

The sample activities were between 4.90 and 1876 U/L.

CK‑MB values for human serum and plasma samples obtained on a cobas c 303 analyzer (y) were compared with those determined using the corresponding reagent on a cobas c 501 analyzer (x).

Sample size (n) = 69

Passing/Bablok

LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790.

Linear regression

y = 1.015x + 0.202 U/L

y = 1.023x + 0.108 U/L

τ = 0.932

r = 1.000

The sample activities were between 3.50 and 1970 U/L.

", "Language": "en" }, { "Name": "Summary", "Value": "

Summary

Creatine kinase (CK) appears as three isoenzymes which are dimers composed of two types of monomer subunits. The isoenzymes comprise all three combinations of monomers, M (for skeletal muscle derived) and B (for brain derived), as represented by the notations MM, MB, and BB.

LREFMoss DW, Henderson AR, Kachmar JF. Enzymes. In: Tietz NW, ed. Fundamentals of Clinical Chemistry, 3rd ed. Philadelphia, PA: WB Saunders 1987;346-421.

Many organs contain CK, but the distribution of isoenzymes is different in each one. Skeletal muscle is very rich in the MM isoenzyme, while brain, stomach, intestine, bladder, and lung contain primarily the BB isoenzyme. The MB isoenzyme has been found in appreciable amounts (15 to 20 percent) only in myocardial tissue. Therefore, total serum CK activity is elevated in a number of diseases. This lack of specificity limits its diagnostic value. However, the striking difference in the CK isoenzyme patterns from different organs has made CK one of the most useful enzymes for diagnostic purposes in acute myocardial infarction. CK‑MB appears in serum reflecting its unique presence in myocardial tissue. It is in supporting the diagnosis of suspected myocardial infarction that serial determinations of CK isoenzymes find their most frequent application in the clinical laboratory.

LREFMoss DW, Henderson AR, Kachmar JF. Enzymes. In: Tietz NW, ed. Fundamentals of Clinical Chemistry, 3rd ed. Philadelphia, PA: WB Saunders 1987;346-421.
,
LREFLott JA, Stang JM. Serum enzymes and isoenzymes in the diagnosis and differential diagnosis of myocardial ischemia and necrosis. Clin Chem 1980;26:1241-1250.

After immunoinhibition with antibodies to the CK‑M subunit,

LREFWürzburg U, Hennrich N, Lang H, et al. Determination of creatine kinase-MB in serum using inhibiting antibodies. Klin Wschr 1976;54(8):357-360.
the CK‑B activity is determined with a standardized method for the determination of CK with activation by NAC as recommended by the German Society for Clinical Chemistry (DGKC)
LREFBergmeyer HU, Breuer H, Büttner H, et al. Empfehlungen der Deutschen Gesellschaft für Klinische Chemie. Standard-Methode zur Bestimmung der Aktivität der Creatin-Kinase. J Clin Chem Clin Biochem 1977;15:249-254.
and the International Federation of Clinical Chemistry (IFCC)
LREFHørder M, Elser RC, Gerhardt W, et al. IFCC methods for the measurement of catalytic concentration of enzymes. Provisional recommendation IFCC method for creatine kinase Appendix A. J Int Fed Clin Chem 1990;2:26-35.
,
LREFSchumann G, Bonora R, Ceriotti F, et al. IFCC Primary Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes at 37 °C – Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase. Clin Chem Lab Med 2002;40(6):635-642.
in 1977 and 2002 respectively. This assay meets the recommendations of the IFCC and DGKC, but was optimized for performance and stability.

", "Language": "en" }, { "Name": "Reagents", "Value": "

Reagents - working solutions

R1

Imidazole buffer: 123 mmol/L, pH 6.5 (37 °C); EDTA: 2.46 mmol/L; Mg2+: 12.3 mmol/L; ADP: 2.46 mmol/L; AMP: 6.14 mmol/L; diadenosine pentaphosphate: 19 µmol/L; NADP (yeast): 2.46 mmol/L; N‑acetylcysteine: 24.6 mmol/L; HK (yeast): ≥ 36.7 µkat/L; G6P‑DH (E. coli): ≥ 23.4 µkat/L; preservative; stabilizers; additives.

R2

CAPSO* buffer: 20 mmol/L, pH 8.8 (37 °C); glucose: 120 mmol/L; EDTA: 2.46 mmol/L; creatine phosphate: 184 mmol/L; 4 monoclonal anti‑CK‑M antibodies (mouse), inhibiting capacity: > 99.6 % up to 66.8 µkat/L (4000 U/L) (37 °C) CK‑M subunit; preservative; stabilizers; additive.

*CAPSO: 3-(cyclohexylamino)-2-hydroxy-1-propanesulfonic acid

R1 is in position B and R2 is in position C.

", "Language": "en" }, { "Name": "PrecautionsWarnings", "Value": "

Precautions and warnings

For in vitro diagnostic use for health care professionals. Exercise the normal precautions required for handling all laboratory reagents.

Infectious or microbial waste:
Warning: handle waste as potentially biohazardous material. Dispose of waste according to accepted laboratory instructions and procedures.

Environmental hazards:
Apply all relevant local disposal regulations to determine the safe disposal.

Safety data sheet available for professional user on request.

This kit contains components classified as follows in accordance with the Regulation (EC) No. 1272/2008:

Danger

H360D

May damage the unborn child.

Prevention:

P201

Obtain special instructions before use.

P202

Do not handle until all safety precautions have been read and understood.

P280

Wear protective gloves/ protective clothing/ eye protection/ face protection/ hearing protection.

Response:

P308 + P313

IF exposed or concerned: Get medical advice/attention.

Storage:

P405

Store locked up.

Disposal:

P501

Dispose of contents/container to an approved waste disposal plant.

Product safety labeling follows EU GHS guidance.

Contact phone: all countries: +49-621-7590

", "Language": "en" }, { "Name": "Caution", "Value": "", "Language": "en" }, { "Name": "QualityControl", "Value": "

Quality control

For quality control, use control materials as listed in the “Order information” section. In addition, other suitable control material can be used.

The control intervals and limits should be adapted to each laboratory’s individual requirements. It is recommended to perform quality control always after lot calibration and subsequently at least every 8 weeks. Values obtained should fall within the defined limits. Each laboratory should establish corrective measures to be taken if values fall outside the defined limits.

Follow the applicable government regulations and local guidelines for quality control.

", "Language": "en" }, { "Name": "SpecimenPreparation", "Value": "

Specimen collection and preparation

For specimen collection and preparation only use suitable tubes or collection containers.

Only the specimens listed below were tested and found acceptable.
Serum: Nonhemolyzed serum is the specimen of choice and also recommended by IFCC.
Plasma: Li‑heparin, K2‑, K3‑EDTA plasma.

Li‑heparin in the usual concentration does not interfere with the test, but IFCC warns against its use.

LREFHørder M, Elser RC, Gerhardt W, et al. IFCC methods for the measurement of catalytic concentration of enzymes. Provisional recommendation IFCC method for creatine kinase Appendix A. J Int Fed Clin Chem 1990;2:26-35.

The sample types listed were tested with a selection of sample collection tubes that were commercially available at the time of testing, i.e. not all available tubes of all manufacturers were tested. Sample collection systems from various manufacturers may contain differing materials which could affect the test results in some cases. When processing samples in primary tubes (sample collection systems), follow the instructions of the tube manufacturer.

Centrifuge samples containing precipitates before performing the assay.

See the limitations and interferences section for details about possible sample interferences.

Stability in serum:

LREFBraun S, Röschenthaler F, Jarausch J, et al. Analyte Stability of CK-MB Activity and cTnT in ICU Patient Serum and Heparin Plasma. Poster presented at Medica 2004, Düsseldorf. (Roche Diagnostics GmbH No. 04587979990).

8 hours at 20‑24 °C

8 days at 2‑8 °C

4 weeks at −20 °C

Stability in heparin plasma:

LREFBraun S, Röschenthaler F, Jarausch J, et al. Analyte Stability of CK-MB Activity and cTnT in ICU Patient Serum and Heparin Plasma. Poster presented at Medica 2004, Düsseldorf. (Roche Diagnostics GmbH No. 04587979990).

8 hours at 20‑24 °C

5 days at 2‑8 °C

8 days at −20 °C

Stability in EDTA plasma:

LREFUse of Anticoagulants in Diagnostic Laboratory Investigations. WHO Publication WHO/DIL/LAB/99.1 Rev. 2: Jan 2002.

2 days at 20‑25 °C

7 days at 4‑8 °C

1 year at −20 °C

", "Language": "en" } ] } }, { "ProductSpecVariant": { "MetaData": { "DocumentMaterialNumber": "07531435001", "ProductName": "CKMB", "ProductLongName": "Creatine Kinase-MB", "Language": "en", "DocumentVersion": "3", "DocumentObjectID": "FF00000005B9E60E", "DocumentOriginID": "FF000000016C000E", "MaterialNumbers": [ "07442050190" ], "InstrumentReferences": [ { "ID": "307", "BrandName": "cobas c 111" } ], "DisclaimerText": "Product information shown on this page contains elements of the officially released Method Sheet. If you require further information please refer to the full Method Sheet PDF under the given link, or contact your local Roche country representative." }, "Chapters": [ { "Name": "IntendedUse", "Value": "

Intended use

In vitro test for the quantitative determination of the catalytic activity of creatine kinase MB subunit (CK‑MB) in human serum and plasma on the cobas c 111 system.

", "Language": "en" }, { "Name": "TestPrinciple", "Value": "

Test principle

Immunological UV assay

  • Sample and addition of R1 (buffer/enzymes/coenzyme)

  • Addition of R2 (buffer/substrate/antibody) and start of reaction

Human CK‑MB is composed of two subunits, CK‑M and CK‑B which both have an active site. With the aid of specific antibodies to CK‑M, the catalytic activity of CK‑M subunits in the sample is inhibited to 99.6 % without affecting the CK‑B subunits. The remaining CK‑B activity, corresponding to half the CK‑MB activity, is determined by the total CK method. As the CK‑BB isoenzyme only rarely appears in serum and the catalytic activity of the CK‑M and CK‑B subunits hardly differ, the catalytic activity of the CK‑MB isoenzyme can be calculated from the measured CK‑B activity by multiplying the result by 2.

", "Language": "en" }, { "Name": "MeasuringRange", "Value": "

Limits and ranges

Measuring range

3‑2000 U/L (0.05‑33.4 µkat/L)

Determine samples having higher activities via the rerun function. Dilution of samples via the rerun function is a 1:3 dilution. Results from samples diluted by the rerun function are automatically multiplied by a factor of 3.

Lower limits of measurement

Limit of Blank, Limit of Detection and Limit of Quantitation

Limit of Blank

= 3 U/L (0.05 µkat/L)

Limit of Detection

= 3 U/L (0.05 µkat/L)

Limit of Quantitation

= 5 U/L (0.08 µkat/L)

The Limit of Blank, Limit of Detection and Limit of Quantitation were determined in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP17‑A2 requirements.
The Limit of Blank is the 95th percentile value from n ≥ 60 measurements of analyte‑free samples over several independent series. The Limit of Blank corresponds to the concentration below which analyte-free samples are found with a probability of 95 %.
The Limit of Detection is determined based on the limit of blank and the standard deviation of low concentration samples. The Limit of Detection corresponds to the lowest analyte concentration which can be detected (value above the limit of blank with a probability of 95 %).
The Limit of Quantitation is the lowest analyte concentration that can be reproducibly measured with a precision of 20 % CV. It has been determined using low concentration creatine kinase‑MB samples.

", "Language": "en" }, { "Name": "ExpectedValues", "Value": "

Expected values

Reference intervals strongly depend on the patient group regarded and the specific clinical situation.

For healthy people: Reference range (37 °C) according to Klein et al.

LREFKlein G, Berger A, Bertholf R, et al. Abstract: Multicenter Evaluation of Liquid Reagents for CK, CK-MB and LDH with Determination of Reference Intervals on Hitachi Systems. Clin Chem 2001;47:Suppl. A30.
and consensus values:
LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308.

< 25 U/L (< 0.418 µkat/L)

For myocardial infarction diagnosis using the combination CK and CK‑MB (activity), and representing a CK consensus value based on long‑term experience:

LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308.
,
LREFStein W. Strategie der klinischen-chemischen Diagnostik des frischen Myokardinfarktes. Med Welt 1985;36:572-577.

1.

CKmen

> 190 U/L (3.17 µkat/L)

CKwomen

> 167 U/L (2.79 µkat/L)

2.

CK‑MB

> 24 U/L (0.40 µkat/L)

3.

The CK‑MB activity accounts for 6‑25 % of the total CK activity.

When myocardial infarction is suspected the diagnostic strategy proposals in the consensus document of European and American cardiologists should in general be followed.

LREFMyocardial Infarction Redefined - A Consensus Document of the Joint European Society of Cardiology/ American College of Cardiology Committee for the Redefinition of Myocardial Infarction. Eur Heart J 2000;21:1502-1513.

If despite the suspicion of myocardial infarction the values found remain below the stated limits, a fresh infarction may be involved. In such cases the determinations should be repeated after 4 hours.

Maximum diagnostic efficiency of the CK‑MB determination will be obtained when a sequential sampling protocol is used and consideration is given to the time pattern of activity over a 6 to 48 hour period. When only CK‑MB activity is used, the diagnostic efficiency will be lower and will vary with the sampling time.

LREFMoss DW, Henderson AR, Kachmar JF. Enzymes. In: Tietz NW, ed. Fundamentals of Clinical Chemistry, 3rd ed. Philadelphia, PA: WB Saunders 1987;346-421.
,
LREFRemaley AT, Wilding P. Macroenzymes: Biochemical Characterization, Clinical Significance, and Laboratory Detection. Clin Chem 1989;35:2261-2270.

Each laboratory should investigate the transferability of the expected values to its own patient population and if necessary determine its own reference ranges.

", "Language": "en" }, { "Name": "LimitationInterference", "Value": "

Limitations - interference

The total CK activity of the specimen should be determined prior to performing the CK‑MB assay. The amount of anti‑human CK‑M subunit antibody in the CK‑MB reagent is sufficient for the complete inhibition of up to 4000 U/L CK‑M activity. If the total CK activity exceeds 4000 U/L, the specimen requires dilution because complete inhibition of the CK‑M subunit is no longer assured. In patients with a disposition to macro‑CK formation, implausibly high CK‑MB values may be measured in relation to the total CK, since the macroforms mainly consist of CK‑B subunits. As these patients have generally not suffered a myocardial infarction, additional diagnostic measures are necessary.

LREFRemaley AT, Wilding P. Macroenzymes: Biochemical Characterization, Clinical Significance, and Laboratory Detection. Clin Chem 1989;35:2261-2270.

Criterion: Recovery within ± 10 % of initial value at a creatine kinase‑MB activity of ≥ 25 U/L (≥ 0.42 µkat/L).

Icterus:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an I index of 60 for conjugated and 20 for unconjugated bilirubin (approximate conjugated bilirubin concentration: 1026 µmol/L or 60 mg/dL and approximate unconjugated bilirubin concentration: 342 µmol/L or 20 mg/dL).

Hemolysis:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an H index of 20 (approximate hemoglobin concentration: 12.4 µmol/L or 20 mg/dL).

Lipemia (Intralipid):

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an L index of 500. There is poor correlation between the L index (corresponds to turbidity) and triglycerides concentration.

Adenylate kinase: Adenylate kinase (AK) may cause positive interference. Sources of AK in the blood are erythrocytes, muscle, and liver. In order to reduce AK interference to a minimum, AMP and Ap5A are included in the reagent. The AMP/Ap5A mixture causes 97 % inhibition of the AK from erythrocytes and muscle, and 95 % inhibition of the AK from liver.

LREFBergmeyer HU, Breuer H, Büttner H, et al. Empfehlungen der Deutschen Gesellschaft für Klinische Chemie. Standard-Methode zur Bestimmung der Aktivität der Creatin-Kinase. J Clin Chem Clin Biochem 1977;15:249-254.
The slight residual AK activity does not influence the assay of total CK, but may affect the low CK‑MB activities.

Drugs: No interference was found at therapeutic concentrations using common drug panels.

LREFBreuer J. Report on the Symposium "Drug effects in Clinical Chemistry Methods". Eur J Clin Chem Clin Biochem 1996;34:385-386.
,
LREFSonntag O, Scholer A. Drug interference in clinical chemistry: recommendation of drugs and their concentrations to be used in drug interference studies. Ann Clin Biochem 2001;38:376-385.

Exceptions: Cyanokit (hydroxocobalamin), Cefoxitin, Sulfasalazine and Sulfapyridine at therapeutic concentrations interfere with the test.

In very rare cases, gammopathy, in particular type IgM (Waldenström’s macroglobulinemia), may cause unreliable results.

LREFBakker AJ, Mücke M. Gammopathy interference in clinical chemistry assays: mechanisms, detection and prevention. Clin Chem Lab Med 2007;45(9):1240-1243.

For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.

ACTION REQUIRED
Special Wash Programming: The use of special wash steps is mandatory when certain test combinations are run together on the cobas c 111 analyzer. For information about test combinations requiring special wash steps, please refer to the latest version of the carry-over evasion list found with the CLEAN Method Sheet and the operator’s manual for further instructions.
Where required, special wash/carry-over evasion programming must be implemented prior to reporting results with this test.

", "Language": "en" }, { "Name": "OrderInformation", "Value": "

OrderInformation (CC Reagents - cobas + Integra)

Order information

Analyzer(s) on which kit(s) can be used

07442050190

Creatine Kinase‑MB (2 x 50 tests)

cobasc 111

Materials required (but not provided):

11447394216

Calibrator f.a.s. CK‑MB (3 x 1 mL)

Code 402

05117003190

PreciControl ClinChem Multi 1 (20 x 5 mL)

Code 391

05947626190

PreciControl ClinChem Multi 1 (4 x 5 mL)

Code 391

05117216190

PreciControl ClinChem Multi 2 (20 x 5 mL)

Code 392

05947774190

PreciControl ClinChem Multi 2 (4 x 5 mL)

Code 392

04774230190

NaCl Diluent 9 % (4 x 12 mL)

Code 951

", "Language": "en" }, { "Name": "SystemInformation", "Value": "

System information

CKMB2: ACN 546

", "Language": "en" }, { "Name": "Handling", "Value": "

Reagent handling

Ready for use

", "Language": "en" }, { "Name": "TestDefinition", "Value": "

Application for serum and plasma

cobas c 111 test definition

Measuring mode

Absorbance

Abs. calculation mode

Kinetic

Reaction direction

Increase

Wavelength A/B

340/552 nm

Calc. first/last

27-38

Unit

U/L (µkat/L)

Reaction mode

R1-S-SR

Pipetting parameters

Diluent (H2O)

R1

100 µL

-

Sample

5 µL

-

SR

20 µL

-

Total volume

125 µL

", "Language": "en" }, { "Name": "StorageStability", "Value": "

Storage and stability

CKMB

Shelf life at 2‑8 °C:

See expiration date on reagent

On-board in use and refrigerated on the analyzer:

4 weeks

NaCl Diluent 9 %

Shelf life at 2‑8 °C:

See expiration date on reagent

On-board in use and refrigerated on the analyzer:

4 weeks

", "Language": "en" }, { "Name": "Calibration", "Value": "

Calibration

Calibrator

C.f.a.s. CK-MB

Deionized water is used automatically by the instrument as the zero calibrator.

Calibration mode

Linear regression

Calibration interval

Each lot and as required following quality control procedures

Traceability: This method has been standardized against the IFCC Method for Creatine Kinase

LREFSchumann G, Bonora R, Ceriotti F, et al. IFCC Primary Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes at 37 °C – Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase. Clin Chem Lab Med 2002;40(6):635-642.
with addition of antibodies.

", "Language": "en" }, { "Name": "Limitations", "Value": "", "Language": "en" }, { "Name": "PerformanceData", "Value": "

Specific performance data

Representative performance data on the cobas c 111 analyzer are given below. Results obtained in individual laboratories may differ.

", "Language": "en" }, { "Name": "Precision", "Value": "

Precision

Repeatability and intermediate precision were determined using human samples and controls in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP5 requirements (2 aliquots per run, 2 runs per day, 21 days). The following results were obtained:

Repeatability

Mean

U/L (µkat/L)

SD

U/L (µkat/L)

CV

%

Human serum 1

23.1 (0.39)

0.5 (0.01)

2.2

Human serum 2

107 (1.79)

1.3 (0.02)

1.2

Human serum 3

274 (4.58)

2.3 (0.04)

0.9

Human serum 4

926 (15.5)

8.9 (0.15)

1.0

Human serum 5

1734 (29.0)

14 (0.23)

0.8

PCCC Multi 1*

40.9 (0.68)

0.8 (0.01)

1.9

PCCC Multi 2

92.3 (1.54)

1.1 (0.02)

1.2

Intermediate precision

Mean

U/L (µkat/L)

SD

U/L (µkat/L)

CV

%

Human serum 1

23.1 (0.39)

0.6 (0.01)

2.5

Human serum 2

107 (1.79)

2.3 (0.04)

2.1

Human serum 3

274 (4.58)

5.4 (0.09)

2.0

Human serum 4

926 (15.5)

20 (0.33)

2.2

Human serum 5

1734 (29.0)

35 (0.58)

2.0

PCCC Multi 1

40.9 (0.68)

0.9 (0.02)

2.2

PCCC Multi 2

92.3 (1.54)

1.1 (0.02)

1.2

*PCCC = PreciControl ClinChem

", "Language": "en" }, { "Name": "MethodComparison", "Value": "

Method comparison

Creatine kinase‑MB values for human serum and plasma samples obtained on acobas c 111 analyzer (y) were compared with those determined using the corresponding reagent on a COBAS INTEGRA 400 plus analyzer (x).

Sample size (n) = 52

Passing/Bablok

LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790.

Linear regression

y = 0.988x - 1.54 U/L

y = 0.989x - 1.33 U/L

τ = 0.962

r = 1.000

The sample activities were between 8.3 and 1988 U/L (0.14 and 33.2 µkat/L).

", "Language": "en" }, { "Name": "Summary", "Value": "

Summary

Creatine kinase (CK) appears as three isoenzymes which are dimers composed of two types of monomer subunits. The isoenzymes comprise all three combinations of monomers, M (for skeletal muscle derived) and B (for brain derived), as represented by the notations MM, MB, and BB.

LREFMoss DW, Henderson AR, Kachmar JF. Enzymes. In: Tietz NW, ed. Fundamentals of Clinical Chemistry, 3rd ed. Philadelphia, PA: WB Saunders 1987;346-421.

Many organs contain CK, but the distribution of isoenzymes is different in each one. Skeletal muscle is very rich in the MM isoenzyme, while brain, stomach, intestine, bladder, and lung contain primarily the BB isoenzyme. The MB isoenzyme has been found in appreciable amounts (15 to 20 percent) only in myocardial tissue. Therefore, total serum CK activity is elevated in a number of diseases. This lack of specificity limits its diagnostic value. However, the striking difference in the CK isoenzyme patterns from different organs has made CK one of the most useful enzymes for diagnostic purposes in acute myocardial infarction. CK‑MB appears in serum reflecting its unique presence in myocardial tissue. It is in supporting the diagnosis of suspected myocardial infarction that serial determinations of CK isoenzymes find their most frequent application in the clinical laboratory.

LREFMoss DW, Henderson AR, Kachmar JF. Enzymes. In: Tietz NW, ed. Fundamentals of Clinical Chemistry, 3rd ed. Philadelphia, PA: WB Saunders 1987;346-421.
,
LREFLott JA, Stang JM. Serum enzymes and isoenzymes in the diagnosis and differential diagnosis of myocardial ischemia and necrosis. Clin Chem 1980;26:1241-1250.

After immunoinhibition with antibodies to the CK‑M subunit,

LREFWürzburg U, Hennrich N, Lang H, et al. Determination of creatine kinase-MB in serum using inhibiting antibodies. Klin Wschr 1976;54(8):357-360.
the CK‑B activity is determined with a standardized method for the determination of CK with activation by NAC as recommended by the German Society for Clinical Chemistry (DGKC)
LREFBergmeyer HU, Breuer H, Büttner H, et al. Empfehlungen der Deutschen Gesellschaft für Klinische Chemie. Standard-Methode zur Bestimmung der Aktivität der Creatin-Kinase. J Clin Chem Clin Biochem 1977;15:249-254.
and the International Federation of Clinical Chemistry (IFCC)
LREFHørder M, Elser RC, Gerhardt W, et al. IFCC methods for the measurement of catalytic concentration of enzymes. Provisional recommendation IFCC method for creatine kinase Appendix A. J Int Fed Clin Chem 1990;2:26-35.
,
LREFSchumann G, Bonora R, Ceriotti F, et al. IFCC Primary Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes at 37 °C – Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase. Clin Chem Lab Med 2002;40(6):635-642.
in 1977 and 2002 respectively. This assay meets the recommendations of the IFCC and DGKC, but was optimized for performance and stability.

", "Language": "en" }, { "Name": "Reagents", "Value": "

Reagents - working solutions

R1

Imidazole buffer: 123 mmol/L, pH 6.5 (37 °C); EDTA: 2.46 mmol/L; Mg2+: 12.3 mmol/L; ADP: 2.46 mmol/L; AMP: 6.14 mmol/L; diadenosine pentaphosphate: 19 µmol/L; NADP (yeast): 2.46 mmol/L; N‑acetylcysteine: 24.6 mmol/L; HK (yeast): ≥ 36.7 µkat/L; G6P‑DH (E. coli): ≥ 23.4 µkat/L; preservative; stabilizers; additives.

SR

CAPSO* buffer: 20 mmol/L, pH 8.8 (37 °C); glucose: 120 mmol/L; EDTA: 2.46 mmol/L; creatine phosphate: 184 mmol/L; 4 monoclonal anti‑CK‑M antibodies (mouse), inhibiting capacity: > 99.6 % up to 66.8 µkat/L (4000 U/L) (37 °C) CK‑M subunit; preservative; stabilizers; additive.

*CAPSO: 3-(cyclohexylamino)-2-hydroxy-1-propanesulfonic acid

", "Language": "en" }, { "Name": "PrecautionsWarnings", "Value": "

Precautions and warnings

For in vitro diagnostic use for health care professionals. Exercise the normal precautions required for handling all laboratory reagents.

Infectious or microbial waste:
Warning: handle waste as potentially biohazardous material. Dispose of waste according to accepted laboratory instructions and procedures.

Environmental hazards:
Apply all relevant local disposal regulations to determine the safe disposal.

Safety data sheet available for professional user on request.

This kit contains components classified as follows in accordance with the Regulation (EC) No. 1272/2008:

Danger

H360D

May damage the unborn child.

Prevention:

P201

Obtain special instructions before use.

P202

Do not handle until all safety precautions have been read and understood.

P280

Wear protective gloves/ protective clothing/ eye protection/ face protection/ hearing protection.

Response:

P308 + P313

IF exposed or concerned: Get medical advice/attention.

Storage:

P405

Store locked up.

Disposal:

P501

Dispose of contents/container to an approved waste disposal plant.

Product safety labeling follows EU GHS guidance.

Contact phone: all countries: +49-621-7590

", "Language": "en" }, { "Name": "Caution", "Value": "", "Language": "en" }, { "Name": "QualityControl", "Value": "

Quality control

For quality control, use control materials as listed in the “Order information” section. In addition, other suitable control material can be used.

The control intervals and limits should be adapted to each laboratory’s individual requirements. Values obtained should fall within the defined limits. Each laboratory should establish corrective measures to be taken if values fall outside the defined limits.

Follow the applicable government regulations and local guidelines for quality control.

", "Language": "en" }, { "Name": "SpecimenPreparation", "Value": "

Specimen collection and preparation

For specimen collection and preparation only use suitable tubes or collection containers.

Only the specimens listed below were tested and found acceptable.
Serum: Nonhemolyzed serum is the specimen of choice and also recommended by IFCC.
Plasma: Li‑heparin, K2‑, K3‑EDTA plasma.

Li‑heparin in the usual concentration does not interfere with the test, but IFCC warns against its use.

LREFHørder M, Elser RC, Gerhardt W, et al. IFCC methods for the measurement of catalytic concentration of enzymes. Provisional recommendation IFCC method for creatine kinase Appendix A. J Int Fed Clin Chem 1990;2:26-35.

The sample types listed were tested with a selection of sample collection tubes that were commercially available at the time of testing, i.e. not all available tubes of all manufacturers were tested. Sample collection systems from various manufacturers may contain differing materials which could affect the test results in some cases. When processing samples in primary tubes (sample collection systems), follow the instructions of the tube manufacturer.

Centrifuge samples containing precipitates before performing the assay.

Stability in serum:

LREFBraun S, Röschenthaler F, Jarausch J, et al. Analyte Stability of CK-MB Activity and cTnT in ICU Patient Serum and Heparin Plasma. Poster presented at Medica 2004, Düsseldorf. (Roche Diagnostics GmbH No. 04587979990).

8 hours at 20‑24 °C

8 days at 2‑8 °C

4 weeks at -20 °C

Stability in heparin plasma:

LREFBraun S, Röschenthaler F, Jarausch J, et al. Analyte Stability of CK-MB Activity and cTnT in ICU Patient Serum and Heparin Plasma. Poster presented at Medica 2004, Düsseldorf. (Roche Diagnostics GmbH No. 04587979990).

8 hours at 20‑24 °C

5 days at 2‑8 °C

8 days at -20 °C

Stability in EDTA plasma:

LREFUse of Anticoagulants in Diagnostic Laboratory Investigations. WHO Publication WHO/DIL/LAB/99.1 Rev. 2: Jan 2002.

2 days at 20‑25 °C

7 days at 4‑8 °C

1 year at -20 °C

", "Language": "en" } ] } }, { "ProductSpecVariant": { "MetaData": { "DocumentMaterialNumber": "0107190808190c501", "ProductName": "CKMB", "ProductLongName": "Creatine Kinase-MB", "Language": "en", "DocumentVersion": "4", "DocumentObjectID": "FF00000005BD560E", "DocumentOriginID": "FF00000001711A0E", "MaterialNumbers": [ "07190808190" ], "InstrumentReferences": [ { "ID": "308", "BrandName": "cobas c 311" }, { "ID": "2324", "BrandName": "cobas c 502" }, { "ID": "309", "BrandName": "cobas c 501" } ], "DisclaimerText": "Product information shown on this page contains elements of the officially released Method Sheet. If you require further information please refer to the full Method Sheet PDF under the given link, or contact your local Roche country representative." }, "Chapters": [ { "Name": "IntendedUse", "Value": "

Intended use

In vitro test for the quantitative determination of the catalytic activity of creatine kinase MB subunit (CK‑MB) in human serum and plasma on cobas c systems.

", "Language": "en" }, { "Name": "TestPrinciple", "Value": "

Test principle

Immunological UV assay

  • Sample and addition of R1 (buffer/enzymes/coenzyme)

  • Addition of R2 (buffer/substrate/antibody) and start of reaction.

Human CK‑MB is composed of two subunits, CK‑M and CK‑B which both have an active site. With the aid of specific antibodies to CK‑M, the catalytic activity of CK‑M subunits in the sample is inhibited to 99.6 % without affecting the CK‑B subunits. The remaining CK‑B activity, corresponding to half the CK‑MB activity, is determined by the total CK method. As the CK‑BB isoenzyme only rarely appears in serum and the catalytic activity of the CK‑M and CK‑B subunits hardly differ, the catalytic activity of the CK‑MB isoenzyme can be calculated from the measured CK‑B activity by multiplying the result by 2.

", "Language": "en" }, { "Name": "MeasuringRange", "Value": "

Limits and ranges

Measuring range

3‑2000 U/L (0.05‑33.4 µkat/L)

Determine samples having higher activities via the rerun function. Dilution of samples via the rerun function is a 1:3 dilution. Results from samples diluted by the rerun function are automatically multiplied by a factor of 3.

Lower limits of measurement

Limit of Blank, Limit of Detection and Limit of Quantitation

Limit of Blank

= 3 U/L (0.05 µkat/L)

Limit of Detection

= 3 U/L (0.05 µkat/L)

Limit of Quantitation

= 5 U/L (0.08 µkat/L)

The Limit of Blank, Limit of Detection and Limit of Quantitation were determined in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP17‑A2 requirements.

The Limit of Blank is the 95th percentile value from n ≥ 60 measurements of analyte‑free samples over several independent series. The Limit of Blank corresponds to the concentration below which analyte‑free samples are found with a probability of 95 %.

The Limit of Detection is determined based on the Limit of Blank and the standard deviation of low concentration samples. The Limit of Detection corresponds to the lowest analyte concentration which can be detected (value above the limit of blank with a probability of 95 %).
The Limit of Quantitation is the lowest analyte concentration that can be reproducibly measured with a precision of 20 % CV. It has been determined using low concentration creatine kinase‑MB samples.

", "Language": "en" }, { "Name": "ExpectedValues", "Value": "

Expected values

Reference intervals strongly depend on the patient group regarded and the specific clinical situation.

For healthy people: Reference range (37 °C) according to Klein et al.

LREFKlein G, Berger A, Bertholf R, et al. Abstract: Multicenter Evaluation of Liquid Reagents for CK, CK-MB and LDH with Determination of Reference Intervals on Hitachi Systems. Clin Chem 2001;47:Suppl. A30.
and consensus values:
LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308.

< 25 U/L (< 0.418 µkat/L)

For myocardial infarction diagnosis using the combination CK and CK‑MB (activity), and representing a CK consensus value based on long‑term experience:

LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308.
,
LREFStein W. Strategie der klinischen-chemischen Diagnostik des frischen Myokardinfarktes. Med Welt 1985;36:572-577.

1.

CKmen

> 190 U/L (3.17 µkat/L)

CKwomen

> 167 U/L (2.79 µkat/L)

2.

CK‑MB

> 24 U/L (0.40 µkat/L)

3.

The CK‑MB activity accounts for 6‑25 % of the total CK activity.

When myocardial infarction is suspected the diagnostic strategy proposals in the consensus document of European and American cardiologists should in general be followed.

LREFMyocardial Infarction Redefined - A Consensus Document of the Joint European Society of Cardiology/ American College of Cardiology Committee for the Redefinition of Myocardial Infarction. Eur Heart J 2000;21:1502-1513.

If despite the suspicion of myocardial infarction the values found remain below the stated limits, a fresh infarction may be involved. In such cases the determinations should be repeated after 4 hours.

Maximum diagnostic efficiency of the CK‑MB determination will be obtained when a sequential sampling protocol is used and consideration is given to the time pattern of activity over a 6 to 48 hour period. When only CK‑MB activity is used, the diagnostic efficiency will be lower and will vary with the sampling time.

LREFMoss DW, Henderson AR, Kachmar JF. Enzymes. In: Tietz NW, ed. Fundamentals of Clinical Chemistry, 3rd ed. Philadelphia, PA: WB Saunders 1987;346-421.
,
LREFRemaley AT, Wilding P. Macroenzymes: Biochemical Characterization, Clinical Significance, and Laboratory Detection. Clin Chem 1989;35:2261-2270.

Each laboratory should investigate the transferability of the expected values to its own patient population and if necessary determine its own reference ranges.

", "Language": "en" }, { "Name": "LimitationInterference", "Value": "

Limitations - interference

The total CK activity of the specimen should be determined prior to performing the CK‑MB assay. The amount of anti‑human CK‑M subunit antibody in the CK‑MB reagent is sufficient for the complete inhibition of up to 4000 U/L CK‑M activity. If the total CK activity exceeds 4000 U/L, the specimen requires dilution because complete inhibition of the CK‑M subunit is no longer assured. In patients with a disposition to macro‑CK formation, implausibly high CK‑MB values may be measured in relation to the total CK, since the macroforms mainly consist of CK‑B subunits. As these patients have generally not suffered a myocardial infarction, additional diagnostic measures are necessary.

LREFRemaley AT, Wilding P. Macroenzymes: Biochemical Characterization, Clinical Significance, and Laboratory Detection. Clin Chem 1989;35:2261-2270.

Criterion: Recovery within ± 10 % of initial value at a creatine kinase‑MB activity of ≥ 25 U/L (≥ 0.42 µkat/L).

Icterus:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an I index of 60 for conjugated and 20 for unconjugated bilirubin (approximate conjugated bilirubin concentration: 1026 µmol/L or 60 mg/dL and approximate unconjugated bilirubin concentration: 342 µmol/L or 20 mg/dL).

Hemolysis:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an H index of 20 (approximate hemoglobin concentration: 12.4 µmol/L or 20 mg/dL).

Lipemia (Intralipid):

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an L index of 500. There is poor correlation between the L index (corresponds to turbidity) and triglycerides concentration.

Adenylate kinase: Adenylate kinase (AK) may cause positive interference. Sources of AK in the blood are erythrocytes, muscle, and liver. In order to reduce AK interference to a minimum, AMP and Ap5A are included in the reagent. The AMP/Ap5A mixture causes 97 % inhibition of the AK from erythrocytes and muscle, and 95 % inhibition of the AK from liver.

LREFBergmeyer HU, Breuer H, Büttner H, et al. Empfehlungen der Deutschen Gesellschaft für Klinische Chemie. Standard-Methode zur Bestimmung der Aktivität der Creatin-Kinase. J Clin Chem Clin Biochem 1977;15:249-254.
The slight residual AK activity does not influence the assay of total CK, but may affect the low CK‑MB activities.

Drugs: No interference was found at therapeutic concentrations using common drug panels.

LREFBreuer J. Report on the Symposium "Drug effects in Clinical Chemistry Methods". Eur J Clin Chem Clin Biochem 1996;34:385-386.
,
LREFSonntag O, Scholer A. Drug interference in clinical chemistry: recommendation of drugs and their concentrations to be used in drug interference studies. Ann Clin Biochem 2001;38:376-385.

Exceptions: Cyanokit (hydroxocobalamin) and Cefoxitin at therapeutic concentrations interfere with the test.

In very rare cases, gammopathy, in particular type IgM (Waldenström’s macroglobulinemia), may cause unreliable results.

LREFBakker AJ, Mücke M. Gammopathy interference in clinical chemistry assays: mechanisms, detection and prevention. Clin Chem Lab Med 2007;45(9):1240-1243.

For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.

ACTION REQUIRED
Special Wash Programming: The use of special wash steps is mandatory when certain test combinations are run together on cobas c systems. The latest version of the carry‑over evasion list can be found with the NaOHD-SMS-SmpCln1+2-SCCS Method Sheets. For further instructions refer to the operator’s manual. cobas c 502 analyzer: All special wash programming necessary for avoiding carry‑over is available via the cobas link, manual input is required in certain cases.

Where required, special wash/carry‑over evasion programming must be implemented prior to reporting results with this test.

", "Language": "en" }, { "Name": "OrderInformation", "Value": "

OrderInformation (CC Reagents - cobas + Integra)

Order information

Analyzer(s) on which cobas c pack(s) can be used

07190808190

Creatine Kinase‑MB (100 tests)

System‑ID 07 7484 7

cobas c 311, cobas c 501/502

Materials required (but not provided):

11447394216

Calibrator f.a.s. CK‑MB (3 x 1 mL)

Code 402

05117003190

PreciControl ClinChem Multi 1 (20 x 5 mL)

Code 391

05947626190

PreciControl ClinChem Multi 1 (4 x 5 mL)

Code 391

05117216190

PreciControl ClinChem Multi 2 (20 x 5 mL)

Code 392

05947774190

PreciControl ClinChem Multi 2 (4 x 5 mL)

Code 392

04489357190

Diluent NaCl 9 % (50 mL)

System-ID 07 6869 3

", "Language": "en" }, { "Name": "SystemInformation", "Value": "

System information

For cobas c 311/501 analyzers:
CKMB2: ACN 546
For cobas c 502 analyzer:
CKMB2: ACN 8546

", "Language": "en" }, { "Name": "Handling", "Value": "

Reagent handling

Ready for use

", "Language": "en" }, { "Name": "TestDefinition", "Value": "

Application for serum and plasma

cobas c 311 test definition

Assay type

Rate A

Reaction time / Assay points

10 / 21‑57

Wavelength (sub/main)

546/340 nm

Reaction direction

Increase

Units

U/L (µkat/L)

Reagent pipetting

Diluent (H2O)

R1

100 µL

R2

20 µL

Sample volumes

Sample

Sample dilution

Sample

Diluent (NaCl)

Normal

5 µL

Decreased

15 µL

15 µL

120 µL

Increased

5 µL

cobas c 501 test definition

Assay type

Rate A

Reaction time / Assay points

10 / 30‑70

Wavelength (sub/main)

546/340 nm

Reaction direction

Increase

Units

U/L (µkat/L)

Reagent pipetting

Diluent (H2O)

R1

100 µL

R2

20 µL

Sample volumes

Sample

Sample dilution

Sample

Diluent (NaCl)

Normal

5 µL

Decreased

15 µL

15 µL

120 µL

Increased

5 µL

cobas c 502 test definition

Assay type

Rate A

Reaction time / Assay points

10 / 30‑70

Wavelength (sub/main)

546/340 nm

Reaction direction

Increase

Units

U/L (µkat/L)

Reagent pipetting

Diluent (H2O)

R1

100 µL

R2

20 µL

Sample volumes

Sample

Sample dilution

Sample

Diluent (NaCl)

Normal

5 µL

Decreased

15 µL

15 µL

120 µL

Increased

10 µL

", "Language": "en" }, { "Name": "StorageStability", "Value": "

Storage and stability

CKMB

Shelf life at 2‑8 °C:

See expiration date on cobas c pack label.

On‑board in use and refrigerated on the analyzer:

8 weeks

Diluent NaCl 9 %

Shelf life at 2‑8 °C:

See expiration date on cobas c pack label.

On‑board in use and refrigerated on the analyzer:

12 weeks

", "Language": "en" }, { "Name": "Calibration", "Value": "

Calibration

Calibrators

S1: H2O

S2: C.f.a.s. CK‑MB

Calibration mode

Linear

Calibration frequency

2‑point calibration
• after reagent lot change
• as required following quality control procedures

Traceability: This method has been standardized against the IFCC Method for Creatine Kinase

LREFSchumann G, Bonora R, Ceriotti F, et al. IFCC Primary Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes at 37 °C – Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase. Clin Chem Lab Med 2002;40(6):635-642.
with addition of antibodies.

", "Language": "en" }, { "Name": "Limitations", "Value": "", "Language": "en" }, { "Name": "PerformanceData", "Value": "

Specific performance data

Representative performance data on the analyzers are given below. Results obtained in individual laboratories may differ.

", "Language": "en" }, { "Name": "Precision", "Value": "

Precision

Repeatability and intermediate precision were determined using human samples and controls in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP5 requirements (2 aliquots per run, 2 runs per day, 21 days). The following results were obtained:

Repeatability

Mean

U/L (µkat/L)

SD

U/L (µkat/L)

CV

%

Human serum 1

17.9 (0.30)

0.4 (0.01)

2.2

Human serum 2

29.1 (0.49)

0.4 (0.01)

1.2

Human serum 3

524 (8.76)

2.5 (0.04)

0.5

Human serum 4

1040 (17.4)

4.9 (0.08)

0.5

Human serum 5

1844 (30.8)

25 (0.42)

1.4

PCCC Multi 1*

41.0 (0.68)

0.3 (0.01)

0.8

PCCC Multi 2

99.2 (1.66)

0.5 (0.01)

0.5

Intermediate precision

Mean

U/L (µkat/L)

SD

U/L (µkat/L)

CV

%

Human serum 1

17.8 (0.30)

0.5 (0.01)

2.8

Human serum 2

29 (0.48)

0.6 (0.01)

1.9

Human serum 3

531 (8.87)

4.4 (0.07)

0.8

Human serum 4

1040 (17.4)

8.4 (0.14)

0.8

Human serum 5

1843 (30.8)

38 (0.63)

2.1

PCCC Multi 1

40.2 (0.67)

0.7 (0.01)

1.7

PCCC Multi 2

98.7 (1.65)

1.5 (0.03)

1.5

*PCCC = PreciControl ClinChem

The data obtained on cobas c 501 analyzer(s) are representative for cobas c 311 analyzer(s).

", "Language": "en" }, { "Name": "MethodComparison", "Value": "

Method comparison

Creatine kinase‑MB values for human serum and plasma samples obtained on a cobas c 501 analyzer (y) were compared with those determined using the corresponding reagent on a Roche/Hitachi MODULAR P analyzer (x).

Sample size (n) = 113

Passing/Bablok

LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790.

Linear regression

y = 1.007x + 2.36 U/L

y = 0.999x + 2.68 U/L

τ = 0.915

r = 1.000

The sample activities were between 5.8 and 1967 U/L (0.10 and 32.8 µkat/L).

The data obtained on cobas c 501 analyzer(s) are representative for cobas c 311 analyzer(s).

", "Language": "en" }, { "Name": "Summary", "Value": "

Summary

Creatine kinase (CK) appears as three isoenzymes which are dimers composed of two types of monomer subunits. The isoenzymes comprise all three combinations of monomers, M (for skeletal muscle derived) and B (for brain derived), as represented by the notations MM, MB, and BB.

LREFMoss DW, Henderson AR, Kachmar JF. Enzymes. In: Tietz NW, ed. Fundamentals of Clinical Chemistry, 3rd ed. Philadelphia, PA: WB Saunders 1987;346-421.

Many organs contain CK, but the distribution of isoenzymes is different in each one. Skeletal muscle is very rich in the MM isoenzyme, while brain, stomach, intestine, bladder, and lung contain primarily the BB isoenzyme. The MB isoenzyme has been found in appreciable amounts (15 to 20 percent) only in myocardial tissue. Therefore, total serum CK activity is elevated in a number of diseases. This lack of specificity limits its diagnostic value. However, the striking difference in the CK isoenzyme patterns from different organs has made CK one of the most useful enzymes for diagnostic purposes in acute myocardial infarction. CK‑MB appears in serum reflecting its unique presence in myocardial tissue. It is in supporting the diagnosis of suspected myocardial infarction that serial determinations of CK isoenzymes find their most frequent application in the clinical laboratory.

LREFMoss DW, Henderson AR, Kachmar JF. Enzymes. In: Tietz NW, ed. Fundamentals of Clinical Chemistry, 3rd ed. Philadelphia, PA: WB Saunders 1987;346-421.
,
LREFLott JA, Stang JM. Serum enzymes and isoenzymes in the diagnosis and differential diagnosis of myocardial ischemia and necrosis. Clin Chem 1980;26:1241-1250.

After immunoinhibition with antibodies to the CK‑M subunit,

LREFWürzburg U, Hennrich N, Lang H, et al. Determination of creatine kinase-MB in serum using inhibiting antibodies. Klin Wschr 1976;54(8):357-360.
the CK‑B activity is determined with a standardized method for the determination of CK with activation by NAC as recommended by the German Society for Clinical Chemistry (DGKC)
LREFBergmeyer HU, Breuer H, Büttner H, et al. Empfehlungen der Deutschen Gesellschaft für Klinische Chemie. Standard-Methode zur Bestimmung der Aktivität der Creatin-Kinase. J Clin Chem Clin Biochem 1977;15:249-254.
and the International Federation of Clinical Chemistry (IFCC)
LREFHørder M, Elser RC, Gerhardt W, et al. IFCC methods for the measurement of catalytic concentration of enzymes. Provisional recommendation IFCC method for creatine kinase Appendix A. J Int Fed Clin Chem 1990;2:26-35.
,
LREFSchumann G, Bonora R, Ceriotti F, et al. IFCC Primary Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes at 37 °C – Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase. Clin Chem Lab Med 2002;40(6):635-642.
in 1977 and 2002 respectively. This assay meets the recommendations of the IFCC and DGKC, but was optimized for performance and stability.

", "Language": "en" }, { "Name": "Reagents", "Value": "

Reagents - working solutions

R1

Imidazole buffer: 123 mmol/L, pH 6.5 (37 °C); EDTA: 2.46 mmol/L; Mg2+: 12.3 mmol/L; ADP: 2.46 mmol/L; AMP: 6.14 mmol/L; diadenosine pentaphosphate: 19 µmol/L; NADP (yeast): 2.46 mmol/L; N‑acetylcysteine: 24.6 mmol/L; HK (yeast): ≥ 36.7 µkat/L; G6P‑DH (E. coli): ≥ 23.4 µkat/L; preservative; stabilizers; additives.

R2

CAPSO* buffer: 20 mmol/L, pH 8.8 (37 °C); glucose: 120 mmol/L; EDTA: 2.46 mmol/L; creatine phosphate: 184 mmol/L; 4 monoclonal anti‑CK‑M antibodies (mouse), inhibiting capacity: > 99.6 % up to 66.8 µkat/L (4000 U/L) (37 °C) CK‑M subunit; preservative; stabilizers; additive.

*CAPSO: 3-(cyclohexylamino)-2-hydroxy-1-propanesulfonic acid

R1 is in position B and R2 is in position C.

", "Language": "en" }, { "Name": "PrecautionsWarnings", "Value": "

Precautions and warnings

For in vitro diagnostic use for health care professionals. Exercise the normal precautions required for handling all laboratory reagents.

Infectious or microbial waste:
Warning: handle waste as potentially biohazardous material. Dispose of waste according to accepted laboratory instructions and procedures.

Environmental hazards:
Apply all relevant local disposal regulations to determine the safe disposal.

Safety data sheet available for professional user on request.

This kit contains components classified as follows in accordance with the Regulation (EC) No. 1272/2008:

Danger

H360D

May damage the unborn child.

Prevention:

P201

Obtain special instructions before use.

P202

Do not handle until all safety precautions have been read and understood.

P280

Wear protective gloves/ protective clothing/ eye protection/ face protection/ hearing protection.

Response:

P308 + P313

IF exposed or concerned: Get medical advice/attention.

Storage:

P405

Store locked up.

Disposal:

P501

Dispose of contents/container to an approved waste disposal plant.

Product safety labeling follows EU GHS guidance.

Contact phone: all countries: +49-621-7590

", "Language": "en" }, { "Name": "Caution", "Value": "", "Language": "en" }, { "Name": "QualityControl", "Value": "

Quality control

For quality control, use control materials as listed in the \"Order information\" section.

In addition, other suitable control material can be used.

The control intervals and limits should be adapted to each laboratory’s individual requirements. Values obtained should fall within the defined limits. Each laboratory should establish corrective measures to be taken if values fall outside the defined limits.

Follow the applicable government regulations and local guidelines for quality control.

", "Language": "en" }, { "Name": "SpecimenPreparation", "Value": "

Specimen collection and preparation

For specimen collection and preparation only use suitable tubes or collection containers.

Only the specimens listed below were tested and found acceptable.
Serum: Nonhemolyzed serum is the specimen of choice and also recommended by IFCC.
Plasma: Li‑heparin, K2‑, K3‑EDTA plasma.

Li‑heparin in the usual concentration does not interfere with the test, but IFCC warns against its use.

LREFHørder M, Elser RC, Gerhardt W, et al. IFCC methods for the measurement of catalytic concentration of enzymes. Provisional recommendation IFCC method for creatine kinase Appendix A. J Int Fed Clin Chem 1990;2:26-35.

The sample types listed were tested with a selection of sample collection tubes that were commercially available at the time of testing, i.e. not all available tubes of all manufacturers were tested. Sample collection systems from various manufacturers may contain differing materials which could affect the test results in some cases. When processing samples in primary tubes (sample collection systems), follow the instructions of the tube manufacturer.

Centrifuge samples containing precipitates before performing the assay.

Stability in serum:

LREFBraun S, Röschenthaler F, Jarausch J, et al. Analyte Stability of CK-MB Activity and cTnT in ICU Patient Serum and Heparin Plasma. Poster presented at Medica 2004, Düsseldorf. (Roche Diagnostics GmbH No. 04587979990).

8 hours at 20‑24 °C

8 days at 2‑8 °C

4 weeks at -20 °C

Stability in heparin plasma:

LREFBraun S, Röschenthaler F, Jarausch J, et al. Analyte Stability of CK-MB Activity and cTnT in ICU Patient Serum and Heparin Plasma. Poster presented at Medica 2004, Düsseldorf. (Roche Diagnostics GmbH No. 04587979990).

8 hours at 20‑24 °C

5 days at 2‑8 °C

8 days at -20 °C

Stability in EDTA plasma:

LREFUse of Anticoagulants in Diagnostic Laboratory Investigations. WHO Publication WHO/DIL/LAB/99.1 Rev. 2: Jan 2002.

2 days at 20‑25 °C

7 days at 4‑8 °C

1 year at -20 °C

", "Language": "en" } ] } }, { "ProductSpecVariant": { "MetaData": { "DocumentMaterialNumber": "0107190808190COIN", "ProductName": "CKMB", "ProductLongName": "Creatine Kinase-MB", "Language": "en", "DocumentVersion": "4", "DocumentObjectID": "FF00000005B9AC0E", "DocumentOriginID": "FF0000000170F40E", "MaterialNumbers": [ "07190808190" ], "InstrumentReferences": [ { "ID": "302", "BrandName": "COBAS INTEGRA 400 plus" } ], "DisclaimerText": "Product information shown on this page contains elements of the officially released Method Sheet. If you require further information please refer to the full Method Sheet PDF under the given link, or contact your local Roche country representative." }, "Chapters": [ { "Name": "IntendedUse", "Value": "

Intended use

In vitro test for the quantitative determination of the catalytic activity of creatine kinase MB subunit (CK‑MB) in human serum and plasma on COBAS INTEGRA systems.

", "Language": "en" }, { "Name": "TestPrinciple", "Value": "

Test principle

Immunological UV assay

  • Sample and addition of R1 (buffer/enzymes/coenzyme)

  • Addition of R2 (buffer/substrate/antibody) and start of reaction.

Human CK‑MB is composed of two subunits, CK‑M and CK‑B which both have an active site. With the aid of specific antibodies to CK‑M, the catalytic activity of CK‑M subunits in the sample is inhibited to 99.6 % without affecting the CK‑B subunits. The remaining CK‑B activity, corresponding to half the CK‑MB activity, is determined by the total CK method. As the CK‑BB isoenzyme only rarely appears in serum and the catalytic activity of the CK‑M and CK‑B subunits hardly differ, the catalytic activity of the CK‑MB isoenzyme can be calculated from the measured CK‑B activity by multiplying the result by 2.

", "Language": "en" }, { "Name": "MeasuringRange", "Value": "

Limits and ranges

Measuring range

3‑2000 U/L (0.05‑33.4 µkat/L)

Determine samples having higher activities via the rerun function. Dilution of samples via the rerun function is a 1:3 dilution. Results from samples diluted by the rerun function are automatically multiplied by a factor of 3.

Lower limits of measurement

Limit of Blank, Limit of Detection and Limit of Quantitation

Limit of Blank

= 3 U/L (0.05 µkat/L)

Limit of Detection

= 3 U/L (0.05 µkat/L)

Limit of Quantitation

= 5 U/L (0.08 µkat/L)

The Limit of Blank, Limit of Detection and Limit of Quantitation were determined in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP17‑A2 requirements.

The Limit of Blank is the 95th percentile value from n ≥ 60 measurements of analyte‑free samples over several independent series. The Limit of Blank corresponds to the concentration below which analyte‑free samples are found with a probability of 95 %.

The Limit of Detection is determined based on the Limit of Blank and the standard deviation of low concentration samples. The Limit of Detection corresponds to the lowest analyte concentration which can be detected (value above the limit of blank with a probability of 95 %).
The Limit of Quantitation is the lowest analyte concentration that can be reproducibly measured with a precision of 20 % CV. It has been determined using low concentration creatine kinase‑MB samples.

", "Language": "en" }, { "Name": "ExpectedValues", "Value": "

Expected values

Reference intervals strongly depend on the patient group regarded and the specific clinical situation.

For healthy people: Reference range (37 °C) according to Klein et al.

LREFKlein G, Berger A, Bertholf R, et al. Abstract: Multicenter Evaluation of Liquid Reagents for CK, CK-MB and LDH with Determination of Reference Intervals on Hitachi Systems. Clin Chem 2001;47:Suppl. A30.
and consensus values:
LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308.

< 25 U/L (< 0.418 µkat/L)

For myocardial infarction diagnosis using the combination CK and CK‑MB (activity), and representing a CK consensus value based on long‑term experience:

LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308.
,
LREFStein W. Strategie der klinischen-chemischen Diagnostik des frischen Myokardinfarktes. Med Welt 1985;36:572-577.

1.

CKmen

> 190 U/L (3.17 µkat/L)

CKwomen

> 167 U/L (2.79 µkat/L)

2.

CK‑MB

> 24 U/L (0.40 µkat/L)

3.

The CK‑MB activity accounts for 6‑25 % of the total CK activity.

When myocardial infarction is suspected the diagnostic strategy proposals in the consensus document of European and American cardiologists should in general be followed.

LREFMyocardial Infarction Redefined - A Consensus Document of the Joint European Society of Cardiology/ American College of Cardiology Committee for the Redefinition of Myocardial Infarction. Eur Heart J 2000;21:1502-1513.

If despite the suspicion of myocardial infarction the values found remain below the stated limits, a fresh infarction may be involved. In such cases the determinations should be repeated after 4 hours.

Maximum diagnostic efficiency of the CK‑MB determination will be obtained when a sequential sampling protocol is used and consideration is given to the time pattern of activity over a 6 to 48 hour period. When only CK‑MB activity is used, the diagnostic efficiency will be lower and will vary with the sampling time.

LREFMoss DW, Henderson AR, Kachmar JF. Enzymes. In: Tietz NW, ed. Fundamentals of Clinical Chemistry, 3rd ed. Philadelphia, PA: WB Saunders 1987;346-421.
,
LREFRemaley AT, Wilding P. Macroenzymes: Biochemical Characterization, Clinical Significance, and Laboratory Detection. Clin Chem 1989;35:2261-2270.

Each laboratory should investigate the transferability of the expected values to its own patient population and if necessary determine its own reference ranges.

", "Language": "en" }, { "Name": "LimitationInterference", "Value": "

Limitations - interference

The total CK activity of the specimen should be determined prior to performing the CK‑MB assay. The amount of anti‑human CK‑M subunit antibody in the CK‑MB reagent is sufficient for the complete inhibition of up to 4000 U/L CK‑M activity. If the total CK activity exceeds 4000 U/L, the specimen requires dilution because complete inhibition of the CK‑M subunit is no longer assured. In patients with a disposition to macro‑CK formation, implausibly high CK‑MB values may be measured in relation to the total CK, since the macroforms mainly consist of CK‑B subunits. As these patients have generally not suffered a myocardial infarction, additional diagnostic measures are necessary.

LREFRemaley AT, Wilding P. Macroenzymes: Biochemical Characterization, Clinical Significance, and Laboratory Detection. Clin Chem 1989;35:2261-2270.

Criterion: Recovery within ± 10 % of initial value at a creatine kinase‑MB activity of ≥ 25 U/L (≥ 0.42 µkat/L).

Icterus:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an I index of 60 for conjugated and 20 for unconjugated bilirubin (approximate conjugated bilirubin concentration: 1026 µmol/L or 60 mg/dL and approximate unconjugated bilirubin concentration: 342 µmol/L or 20 mg/dL).

Hemolysis:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an H index of 20 (approximate hemoglobin concentration: 12.4 µmol/L or 20 mg/dL).

Lipemia (Intralipid):

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an L index of 500. There is poor correlation between the L index (corresponds to turbidity) and triglycerides concentration.

Adenylate kinase: Adenylate kinase (AK) may cause positive interference. Sources of AK in the blood are erythrocytes, muscle, and liver. In order to reduce AK interference to a minimum, AMP and Ap5A are included in the reagent. The AMP/Ap5A mixture causes 97 % inhibition of the AK from erythrocytes and muscle, and 95 % inhibition of the AK from liver.

LREFBergmeyer HU, Breuer H, Büttner H, et al. Empfehlungen der Deutschen Gesellschaft für Klinische Chemie. Standard-Methode zur Bestimmung der Aktivität der Creatin-Kinase. J Clin Chem Clin Biochem 1977;15:249-254.
The slight residual AK activity does not influence the assay of total CK, but may affect the low CK‑MB activities.

Drugs: No interference was found at therapeutic concentrations using common drug panels.

LREFBreuer J. Report on the Symposium "Drug effects in Clinical Chemistry Methods". Eur J Clin Chem Clin Biochem 1996;34:385-386.
,
LREFSonntag O, Scholer A. Drug interference in clinical chemistry: recommendation of drugs and their concentrations to be used in drug interference studies. Ann Clin Biochem 2001;38:376-385.

Exceptions: Cyanokit (hydroxocobalamin), Cefoxitin, Sulfasalazine and Sulfapyridine at therapeutic concentrations interfere with the test.

In very rare cases, gammopathy, in particular type IgM (Waldenström’s macroglobulinemia), may cause unreliable results.

LREFBakker AJ, Mücke M. Gammopathy interference in clinical chemistry assays: mechanisms, detection and prevention. Clin Chem Lab Med 2007;45(9):1240-1243.

For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.

ACTION REQUIRED
Special Wash Programming: The use of special wash steps is mandatory when certain test combinations are run together on COBAS INTEGRA analyzers. Refer to the CLEAN Method Sheet for further instructions and for the latest version of the Extra wash cycle list.
Where required, special wash/carry-over evasion programming must be implemented prior to reporting results with this test.

", "Language": "en" }, { "Name": "OrderInformation", "Value": "

OrderInformation (CC Reagents - cobas + Integra)

Order information

Analyzer(s) on which cobas c pack(s) can be used

07190808190

Creatine Kinase‑MB (100 tests)

System‑ID 07 7484 7

COBAS INTEGRA 400 plus

Materials required (but not provided):

11447394216

Calibrator f.a.s. CK‑MB (3 x 1 mL)

System-ID 07 7996 2

05117003190

PreciControl ClinChem Multi 1 (20 x 5 mL)

System-ID 07 7469 3

05947626190

PreciControl ClinChem Multi 1 (4 x 5 mL)

System-ID 07 7469 3

05117216190

PreciControl ClinChem Multi 2 (20 x 5 mL)

System-ID 07 7470 7

05947774190

PreciControl ClinChem Multi 2 (4 x 5 mL)

System-ID 07 7470 7

20756350322

NaCl Diluent 9 % (6 x 22 mL)

System-ID 07 5635 0

", "Language": "en" }, { "Name": "SystemInformation", "Value": "

System information

Test CKMB2, test ID 0-057

", "Language": "en" }, { "Name": "Handling", "Value": "

Reagent handling

Ready for use

", "Language": "en" }, { "Name": "TestDefinition", "Value": "

Application for serum and plasma

Test definition

Measuring mode

Absorbance

Abs. calculation mode

Kinetic

Reaction mode

R1‑S‑SR

Reaction direction

Increase

Wavelength A/B

340/552 nm

Calc. first/last

10/50‑69

Unit

U/L

Pipetting parameters

Diluent (H2O)

R1

100 µL

-

Sample

5 µL

-

SR

20 µL

-

Total volume

125 µL

", "Language": "en" }, { "Name": "StorageStability", "Value": "

Storage and stability

Shelf life at 2‑8 °C

See expiration date on cobas c pack label

On‑board in use at 10‑15 °C

8 weeks

", "Language": "en" }, { "Name": "Calibration", "Value": "

Calibration

Calibrator

C.f.a.s. CK‑MB

Use deionized water as zero calibrator.

Calibration mode

Linear regression

Calibration replicate

Duplicate recommended

Calibration interval

Each lot and as required following quality control procedures

Traceability: This method has been standardized against the IFCC Method for Creatine Kinase

LREFSchumann G, Bonora R, Ceriotti F, et al. IFCC Primary Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes at 37 °C – Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase. Clin Chem Lab Med 2002;40(6):635-642.
with addition of antibodies.

", "Language": "en" }, { "Name": "Limitations", "Value": "", "Language": "en" }, { "Name": "PerformanceData", "Value": "

Specific performance data

Representative performance data on the COBAS INTEGRA analyzers are given below. Results obtained in individual laboratories may differ.

", "Language": "en" }, { "Name": "Precision", "Value": "

Precision

Repeatability and intermediate precision were determined using human samples and controls in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP5 requirements (2 aliquots per run, 2 runs per day, 21 days). The following results were obtained:

Repeatability

Mean

U/L (µkat/L)

SD

U/L (µkat/L)

CV

%

Human serum 1

22.2 (0.37)

0.7 (0.01)

3.2

Human serum 2

31.6 (0.53)

0.5 (0.01)

1.7

Human serum 3

562 (9.39)

3.0 (0.05)

0.5

Human serum 4

1105 (18.5)

7.0 (0.12)

0.6

Human serum 5

1949 (32.6)

27 (0.45)

1.4

PCCC Multi 1*

44.5 (0.74)

0.6 (0.01)

1.3

PCCC Multi 2

106 (1.77)

0.8 (0.01)

0.7

Intermediate precision

Mean

U/L (µkat/L)

SD

U/L (µkat/L)

CV

%

Human serum 1

22.2 (0.37)

0.8 (0.01)

3.8

Human serum 2

31.6 (0.53)

0.7 (0.01)

2.2

Human serum 3

562 (9.39)

5.0 (0.08)

0.9

Human serum 4

1085 (18.1)

9.8 (0.16)

0.9

Human serum 5

1949 (32.6)

34 (0.57)

1.7

PCCC Multi 1

43.5 (0.73)

0.8 (0.01)

1.8

PCCC Multi 2

104 (1.74)

1.6 (0.03)

1.5

*PCCC = PreciControl ClinChem

", "Language": "en" }, { "Name": "MethodComparison", "Value": "

Method comparison

Creatine kinase‑MB values for human serum and plasma samples obtained on a COBAS INTEGRA 400 plus analyzer (y) were compared with those using the corresponding reagent on a Roche/Hitachi MODULAR P analyzer (x).

Sample size (n) = 117

Passing/Bablok

LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790.

Linear regression

y = 1.016x + 3.75 U/L

y = 1.011x + 4.26 U/L

τ = 0.897

r = 1.000

The sample activities were between 5.0 and 1967 U/L (0.08 and 32.8 µkat/L).

", "Language": "en" }, { "Name": "Summary", "Value": "

Summary

Creatine kinase (CK) appears as three isoenzymes which are dimers composed of two types of monomer subunits. The isoenzymes comprise all three combinations of monomers, M (for skeletal muscle derived) and B (for brain derived), as represented by the notations MM, MB, and BB.

LREFMoss DW, Henderson AR, Kachmar JF. Enzymes. In: Tietz NW, ed. Fundamentals of Clinical Chemistry, 3rd ed. Philadelphia, PA: WB Saunders 1987;346-421.

Many organs contain CK, but the distribution of isoenzymes is different in each one. Skeletal muscle is very rich in the MM isoenzyme, while brain, stomach, intestine, bladder, and lung contain primarily the BB isoenzyme. The MB isoenzyme has been found in appreciable amounts (15 to 20 percent) only in myocardial tissue. Therefore, total serum CK activity is elevated in a number of diseases. This lack of specificity limits its diagnostic value. However, the striking difference in the CK isoenzyme patterns from different organs has made CK one of the most useful enzymes for diagnostic purposes in acute myocardial infarction. CK‑MB appears in serum reflecting its unique presence in myocardial tissue. It is in supporting the diagnosis of suspected myocardial infarction that serial determinations of CK isoenzymes find their most frequent application in the clinical laboratory.

LREFMoss DW, Henderson AR, Kachmar JF. Enzymes. In: Tietz NW, ed. Fundamentals of Clinical Chemistry, 3rd ed. Philadelphia, PA: WB Saunders 1987;346-421.
,
LREFLott JA, Stang JM. Serum enzymes and isoenzymes in the diagnosis and differential diagnosis of myocardial ischemia and necrosis. Clin Chem 1980;26:1241-1250.

After immunoinhibition with antibodies to the CK‑M subunit,

LREFWürzburg U, Hennrich N, Lang H, et al. Determination of creatine kinase-MB in serum using inhibiting antibodies. Klin Wschr 1976;54(8):357-360.
the CK‑B activity is determined with a standardized method for the determination of CK with activation by NAC as recommended by the German Society for Clinical Chemistry (DGKC)
LREFBergmeyer HU, Breuer H, Büttner H, et al. Empfehlungen der Deutschen Gesellschaft für Klinische Chemie. Standard-Methode zur Bestimmung der Aktivität der Creatin-Kinase. J Clin Chem Clin Biochem 1977;15:249-254.
and the International Federation of Clinical Chemistry (IFCC)
LREFHørder M, Elser RC, Gerhardt W, et al. IFCC methods for the measurement of catalytic concentration of enzymes. Provisional recommendation IFCC method for creatine kinase Appendix A. J Int Fed Clin Chem 1990;2:26-35.
,
LREFSchumann G, Bonora R, Ceriotti F, et al. IFCC Primary Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes at 37 °C – Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase. Clin Chem Lab Med 2002;40(6):635-642.
in 1977 and 2002 respectively. This assay meets the recommendations of the IFCC and DGKC, but was optimized for performance and stability.

", "Language": "en" }, { "Name": "Reagents", "Value": "

Reagents - working solutions

R1

Imidazole buffer: 123 mmol/L, pH 6.5 (37 °C); EDTA: 2.46 mmol/L; Mg2+: 12.3 mmol/L; ADP: 2.46 mmol/L; AMP: 6.14 mmol/L; diadenosine pentaphosphate: 19 µmol/L; NADP (yeast): 2.46 mmol/L; N‑acetylcysteine: 24.6 mmol/L; HK (yeast): ≥ 36.7 µkat/L; G6P‑DH (E. coli): ≥ 23.4 µkat/L; preservative; stabilizers; additives.

SR

CAPSO* buffer: 20 mmol/L, pH 8.8 (37 °C); glucose: 120 mmol/L; EDTA: 2.46 mmol/L; creatine phosphate: 184 mmol/L; 4 monoclonal anti‑CK‑M antibodies (mouse), inhibiting capacity: > 99.6 % up to 66.8 µkat/L (4000 U/L) (37 °C) CK‑M subunit; preservative; stabilizers; additive.

*CAPSO: 3-(cyclohexylamino)-2-hydroxy-1-propanesulfonic acid

R1 is in position B and SR is in position C.

", "Language": "en" }, { "Name": "PrecautionsWarnings", "Value": "

Precautions and warnings

For in vitro diagnostic use for health care professionals. Exercise the normal precautions required for handling all laboratory reagents.

Infectious or microbial waste:
Warning: handle waste as potentially biohazardous material. Dispose of waste according to accepted laboratory instructions and procedures.

Environmental hazards:
Apply all relevant local disposal regulations to determine the safe disposal.

Safety data sheet available for professional user on request.

This kit contains components classified as follows in accordance with the Regulation (EC) No. 1272/2008:

Danger

H360D

May damage the unborn child.

Prevention:

P201

Obtain special instructions before use.

P202

Do not handle until all safety precautions have been read and understood.

P280

Wear protective gloves/ protective clothing/ eye protection/ face protection/ hearing protection.

Response:

P308 + P313

IF exposed or concerned: Get medical advice/attention.

Storage:

P405

Store locked up.

Disposal:

P501

Dispose of contents/container to an approved waste disposal plant.

Product safety labeling follows EU GHS guidance.

Contact phone: all countries: +49-621-7590

", "Language": "en" }, { "Name": "Caution", "Value": "", "Language": "en" }, { "Name": "QualityControl", "Value": "

Quality control

Reference range

PreciControl ClinChem Multi 1

Pathological range

PreciControl ClinChem Multi 2

Control interval

24 hours recommended

Control sequence

User defined

Control after calibration

Recommended

For quality control, use control materials as listed in the “Order information” section. In addition, other suitable control material can be used.

The control intervals and limits should be adapted to each laboratory’s individual requirements. Values obtained should fall within the defined limits. Each laboratory should establish corrective measures to be taken if values fall outside the defined limits.

Follow the applicable government regulations and local guidelines for quality control.

", "Language": "en" }, { "Name": "SpecimenPreparation", "Value": "

Specimen collection and preparation

For specimen collection and preparation only use suitable tubes or collection containers.

Only the specimens listed below were tested and found acceptable.
Serum: Nonhemolyzed serum is the specimen of choice and also recommended by IFCC.
Plasma: Li‑heparin, K2‑, K3‑EDTA plasma.

Li‑heparin in the usual concentration does not interfere with the test, but IFCC warns against its use.

LREFHørder M, Elser RC, Gerhardt W, et al. IFCC methods for the measurement of catalytic concentration of enzymes. Provisional recommendation IFCC method for creatine kinase Appendix A. J Int Fed Clin Chem 1990;2:26-35.

The sample types listed were tested with a selection of sample collection tubes that were commercially available at the time of testing, i.e. not all available tubes of all manufacturers were tested. Sample collection systems from various manufacturers may contain differing materials which could affect the test results in some cases. When processing samples in primary tubes (sample collection systems), follow the instructions of the tube manufacturer.

Centrifuge samples containing precipitates before performing the assay.

Stability in serum:

LREFBraun S, Röschenthaler F, Jarausch J, et al. Analyte Stability of CK-MB Activity and cTnT in ICU Patient Serum and Heparin Plasma. Poster presented at Medica 2004, Düsseldorf. (Roche Diagnostics GmbH No. 04587979990).

8 hours at 20‑24 °C

8 days at 2‑8 °C

4 weeks at -20 °C

Stability in heparin plasma:

LREFBraun S, Röschenthaler F, Jarausch J, et al. Analyte Stability of CK-MB Activity and cTnT in ICU Patient Serum and Heparin Plasma. Poster presented at Medica 2004, Düsseldorf. (Roche Diagnostics GmbH No. 04587979990).

8 hours at 20‑24 °C

5 days at 2‑8 °C

8 days at -20 °C

Stability in EDTA plasma:

LREFUse of Anticoagulants in Diagnostic Laboratory Investigations. WHO Publication WHO/DIL/LAB/99.1 Rev. 2: Jan 2002.

2 days at 20‑25 °C

7 days at 4‑8 °C

1 year at -20 °C

", "Language": "en" } ] } }, { "ProductSpecVariant": { "MetaData": { "DocumentMaterialNumber": "0105168562190c701", "ProductName": "CKMB", "ProductLongName": "Creatine Kinase-MB", "Language": "en", "DocumentVersion": "9", "DocumentObjectID": "FF00000005B8A20E", "DocumentOriginID": "FF00000005129D0E", "MaterialNumbers": [ "05168562190", "05168562214" ], "InstrumentReferences": [ { "ID": "2492", "BrandName": "cobas c 702" }, { "ID": "310", "BrandName": "cobas c 701" } ], "DisclaimerText": "Product information shown on this page contains elements of the officially released Method Sheet. If you require further information please refer to the full Method Sheet PDF under the given link, or contact your local Roche country representative." }, "Chapters": [ { "Name": "IntendedUse", "Value": "

Intended use

In vitro test for the quantitative determination of the catalytic activity of creatine kinase MB subunit (CK‑MB) in human serum and plasma oncobas c systems.

", "Language": "en" }, { "Name": "TestPrinciple", "Value": "

Test principle

Immunological UV assay

  • Sample and addition of R1 (buffer/enzymes/coenzyme)

  • Addition of R2 (buffer/substrate/antibody) and start of reaction.

Human CK‑MB is composed of two subunits, CK‑M and CK‑B which both have an active site. With the aid of specific antibodies to CK‑M, the catalytic activity of CK‑M subunits in the sample is inhibited to 99.6 % without affecting the CK‑B subunits. The remaining CK‑B activity, corresponding to half the CK‑MB activity, is determined by the total CK method. As the CK‑BB isoenzyme only rarely appears in serum and the catalytic activity of the CK‑M and CK‑B subunits hardly differ, the catalytic activity of the CK‑MB isoenzyme can be calculated from the measured CK‑B activity by multiplying the result by 2.

", "Language": "en" }, { "Name": "MeasuringRange", "Value": "

Limits and ranges

Measuring range

3‑2000 U/L (0.050‑33.4 µkat/L)

Determine samples having higher activities via the rerun function. Dilution of samples via the rerun function is a 1:3 dilution. Results from samples diluted by the rerun function are automatically multiplied by a factor of 3.

Lower limits of measurement

Lower detection limit of the test

3 U/L (0.05 µkat/L)

The lower detection limit represents the lowest measurable analyte level that can be distinguished from zero. It is calculated as the value lying 3 standard deviations above that of the lowest standard (standard 1 + 3 SD, repeatability, n = 21).

Values below the lower detection limit (< 3 U/L) will not be flagged by the instrument.

", "Language": "en" }, { "Name": "ExpectedValues", "Value": "

Expected values

Reference intervals strongly depend on the patient group regarded and the specific clinical situation.

For healthy people: Reference range (37 °C) according to Klein et al.

LREFKlein G, Berger A, Bertholf R, et al. Abstract: Multicenter Evaluation of Liquid Reagents for CK, CK-MB and LDH with Determination of Reference Intervals on Hitachi Systems. Clin Chem 2001;47:Suppl. A30.
and consensus values
LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308.
:

< 25 U/L

(< 0.418 µkat/L)

For myocardial infarction diagnosis using the combination CK and CK‑MB (activity), and representing a CK consensus value based on long‑term experience:

LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308.
,
LREFStein W. Strategie der klinischen-chemischen Diagnostik des frischen Myokardinfarktes. Med Welt 1985;36:572-577.

1.

CKmen

> 190 U/L (3.17 µkat/L)

CKwomen

> 167 U/L (2.79 µkat/L)

2.

CK‑MB

> 24 U/L (0.40 µkat/L)

3.

The CK‑MB activity accounts for 6‑25 % of the total CK activity.

When myocardial infarction is suspected the diagnostic strategy proposals in the consensus document of European and American cardiologists should in general be followed.

LREFMyocardial Infarction Redefined - A Consensus Document of the Joint European Society of Cardiology/ American College of Cardiology Committee for the Redefinition of Myocardial Infarction. Eur Heart J 2000;21:1502-1513.

If despite the suspicion of myocardial infarction the values found remain below the stated limits, a fresh infarction may be involved. In such cases the determinations should be repeated after 4 hours.

Maximum diagnostic efficiency of the CK‑MB determination will be obtained when a sequential sampling protocol is used and consideration is given to the time pattern of activity over a 6 to 48 hour period. When only CK‑MB activity is used, the diagnostic efficiency will be lower and will vary with the sampling time.

LREFMoss DW, Henderson AR, Kachmar JF. Enzymes. In: Tietz NW, ed. Fundamentals of Clinical Chemistry, 3rd ed. Philadelphia, PA: WB Saunders 1987;346-421.
,
LREFRemaley AT, Wilding P. Macroenzymes: Biochemical Characterization, Clinical Significance, and Laboratory Detection. Clin Chem 1989;35:2261-2270.

Each laboratory should investigate the transferability of the expected values to its own patient population and if necessary determine its own reference ranges.

", "Language": "en" }, { "Name": "LimitationInterference", "Value": "

Limitations - interference

The total CK activity of the specimen should be determined prior to performing the CK‑MB assay. The amount of anti‑human CK‑M subunit antibody in the CK‑MB reagent is sufficient for the complete inhibition of up to 4000 U/L CK‑M activity. If the total CK activity exceeds 4000 U/L, the specimen requires dilution because complete inhibition of the CK‑M subunit is no longer assured. In patients with a disposition to macro‑CK formation, implausibly high CK‑MB values may be measured in relation to the total CK, since the macroforms mainly consist of CK‑B subunits. As these patients have generally not suffered a myocardial infarction, additional diagnostic measures are necessary.

LREFRemaley AT, Wilding P. Macroenzymes: Biochemical Characterization, Clinical Significance, and Laboratory Detection. Clin Chem 1989;35:2261-2270.

Criterion: Recovery within ± 10 % of initial value at a creatine kinase‑MB activity of ≥ 25 U/L (≥ 0.42 µkat/L).

Icterus:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an I index of 60 for conjugated and 20 for unconjugated bilirubin (approximate conjugated bilirubin concentration: 1026 µmol/L or 60 mg/dL and approximate unconjugated bilirubin concentration: 342 µmol/L or 20 mg/dL).

Hemolysis:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an H index of 20 (approximate hemoglobin concentration: 12.4 µmol/L or 20 mg/dL).

Lipemia (Intralipid):

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an L index of 500. There is poor correlation between the L index (corresponds to turbidity) and triglycerides concentration.

Adenylate kinase: Adenylate kinase (AK) may cause positive interference. Sources of AK in the blood are erythrocytes, muscle, and liver. In order to reduce AK interference to a minimum, AMP and Ap5A are included in the reagent. The AMP/Ap5A mixture causes 97 % inhibition of the AK from erythrocytes and muscle, and 95 % inhibition of the AK from liver.

LREFBergmeyer HU, Breuer H, Büttner H, et al. Empfehlungen der Deutschen Gesellschaft für Klinische Chemie. Standard-Methode zur Bestimmung der Aktivität der Creatin-Kinase. J Clin Chem Clin Biochem 1977;15:249-254.
The slight residual AK activity does not influence the assay of total CK, but may affect the low CK‑MB activities.

Drugs: No interference was found at therapeutic concentrations using common drug panels.

LREFBreuer J. Report on the Symposium "Drug effects in Clinical Chemistry Methods". Eur J Clin Chem Clin Biochem 1996;34:385-386.
,
LREFSonntag O, Scholer A. Drug interference in clinical chemistry: recommendation of drugs and their concentrations to be used in drug interference studies. Ann Clin Biochem 2001;38:376-385.

Cyanokit (hydroxocobalamin) and Cefoxitin at therapeutic concentrations interfere with the test.

In very rare cases, gammopathy, in particular type IgM (Waldenström’s macroglobulinemia), may cause unreliable results.

LREFBakker AJ, Mücke M. Gammopathy interference in clinical chemistry assays: mechanisms, detection and prevention. Clin Chem Lab Med 2007;45(9):1240-1243.

For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.

ACTION REQUIRED
Special Wash Programming: The use of special wash steps is mandatory when certain test combinations are run together on cobas c systems. All special wash programming necessary for avoiding carry‑over is available via the cobas link, manual input is required in certain cases. The latest version of the carry‑over evasion list can be found with the NaOHD/SMS/SmpCln1+2/SCCS Method Sheet and for further instructions refer to the operator’s manual.

Where required, special wash/carry‑over evasion programming must be implemented prior to reporting results with this test.

", "Language": "en" }, { "Name": "OrderInformation", "Value": "

OrderInformation (CC Reagents - cobas + Integra)

Order information

Analyzer(s) on which cobas c pack(s) can be used

05168562190*

Creatine Kinase‑MB (600 tests)

System‑ID 03 5924 4

cobas c 701/702

05168562214*

Creatine Kinase‑MB (600 tests)

System‑ID 03 5924 4

cobas c 701/702

Materials required (but not provided):

11447394216

Calibrator f.a.s. CK‑MB (3 x 1 mL)

Code 402

05117003190

PreciControl ClinChem Multi 1 (20 x 5 mL)

Code 391

05947626190

PreciControl ClinChem Multi 1 (4 x 5 mL)

Code 391

05117216190

PreciControl ClinChem Multi 2 (20 x 5 mL)

Code 392

05947774190

PreciControl ClinChem Multi 2 (4 x 5 mL)

Code 392

05172152190

Diluent NaCl 9 % (119 mL)

System‑ID 08 6869 3

* Some kits shown may not be available in all countries.

", "Language": "en" }, { "Name": "SystemInformation", "Value": "

System information

CKMB: ACN 8060

CKMB2: ACN 8546

", "Language": "en" }, { "Name": "Handling", "Value": "

Reagent handling

Ready for use

", "Language": "en" }, { "Name": "TestDefinition", "Value": "

Application for serum and plasma

cobas c 701/702 test definition

Assay type

Rate A

Reaction time / Assay points

10 / 30‑38

Wavelength (sub/main)

546/340 nm

Reaction direction

Increase

Units

U/L (µkat/L)

Reagent pipetting

Diluent (H2O)

R1

100 µL

R3

20 µL

Sample volumes

Sample

Sample dilution

Sample

Diluent (NaCl)

Normal

5 µL

Decreased

15 µL

15 µL

120 µL

Increased

10 µL

", "Language": "en" }, { "Name": "StorageStability", "Value": "

Storage and stability

CKMB

Shelf life at 2-8 °C:

See expiration date on cobas c pack label.

On‑board in use and refrigerated on the analyzer:

4 weeks

On‑board on the Reagent Manager:

24 hours

Diluent NaCl 9 %

Shelf life at 2-8 °C:

See expiration date on cobas c pack label.

On‑board in use and refrigerated on the analyzer:

4 weeks

On‑board on the Reagent Manager:

24 hours

", "Language": "en" }, { "Name": "Calibration", "Value": "

Calibration

Calibrators

S1: H2O

S2: C.f.a.s. CK‑MB

Calibration mode

Linear

Calibration frequency

2‑point calibration
• after reagent lot change
• as required following quality control procedures

Traceability: This method has been standardized against the IFCC Method for Creatine Kinase

LREFSchumann G, Bonora R, Ceriotti F, et al. IFCC Primary Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes at 37 °C – Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase. Clin Chem Lab Med 2002;40(6):635-642.
with addition of antibodies.

", "Language": "en" }, { "Name": "Limitations", "Value": "", "Language": "en" }, { "Name": "PerformanceData", "Value": "

Specific performance data

Representative performance data on the analyzers are given below. Results obtained in individual laboratories may differ.

", "Language": "en" }, { "Name": "Precision", "Value": "

Precision

Precision was determined using human samples and controls in an internal protocol with repeatability (n = 21) and intermediate precision (3 aliquots per run, 1 run per day, 21 days). The following results were obtained:

Repeatability

Mean

U/L (µkat/L)

SD

U/L (µkat/L)

CV

%

Precinorm CK‑MB

35.0 (0.584)

0.5 (0.008)

1.5

Precipath CK‑MB

207 (3.46)

1 (0.01)

0.3

Human serum A

19.5 (0.326)

0.5 (0.008)

2.6

Human serum B

660 (11.0)

1 (0.0)

0.2

Human serum C

1811 (30.2)

6 (0.1)

0.3

Intermediate precision

Mean

U/L (µkat/L)

SD

U/L (µkat/L)

CV

%

Precinorm CK‑MB

32.1 (0.536)

1.1 (0.018)

3.5

Precipath CK‑MB

173 (2.89)

1 (0.02)

0.7

Human serum N

20.4 (0.341)

0.9 (0.015)

4.5

Human serum H

184 (3.07)

2 (0.03)

0.9

Results for intermediate precision were obtained on a Roche/Hitachi 917 analyzer.

", "Language": "en" }, { "Name": "MethodComparison", "Value": "

Method comparison

Creatine kinase‑MB values for human serum and plasma samples obtained on acobas c 701 analyzer (y) were compared with those determined using the corresponding reagent on a Roche/Hitachi 917 analyzer (x).

Sample size (n) = 129

Passing/Bablok

LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790.

Linear regression

y = 0.988x + 2.23 U/L

y = 0.993x + 2.56 U/L

τ = 0.924

r = 1.000

The sample activities were between 3.00 and 1861 U/L (0.050 and 31.1 µkat/L).

", "Language": "en" }, { "Name": "Summary", "Value": "

Summary

Creatine kinase (CK) appears as three isoenzymes which are dimers composed of two types of monomer subunits. The isoenzymes comprise all three combinations of monomers, M (for skeletal muscle derived) and B (for brain derived), as represented by the notations MM, MB, and BB.

LREFMoss DW, Henderson AR, Kachmar JF. Enzymes. In: Tietz NW, ed. Fundamentals of Clinical Chemistry, 3rd ed. Philadelphia, PA: WB Saunders 1987;346-421.

Many organs contain CK, but the distribution of isoenzymes is different in each one. Skeletal muscle is very rich in the MM isoenzyme, while brain, stomach, intestine, bladder, and lung contain primarily the BB isoenzyme. The MB isoenzyme has been found in appreciable amounts (15 to 20 percent) only in myocardial tissue. Therefore, total serum CK activity is elevated in a number of diseases. This lack of specificity limits its diagnostic value. However, the striking difference in the CK isoenzyme patterns from different organs has made CK one of the most useful enzymes for diagnostic purposes in acute myocardial infarction. CK‑MB appears in serum reflecting its unique presence in myocardial tissue. It is in supporting the diagnosis of suspected myocardial infarction that serial determinations of CK isoenzymes find their most frequent application in the clinical laboratory.

LREFMoss DW, Henderson AR, Kachmar JF. Enzymes. In: Tietz NW, ed. Fundamentals of Clinical Chemistry, 3rd ed. Philadelphia, PA: WB Saunders 1987;346-421.
,
LREFLott JA, Stang JM. Serum enzymes and isoenzymes in the diagnosis and differential diagnosis of myocardial ischemia and necrosis. Clin Chem 1980;26:1241-1250.

After immunoinhibition with antibodies to the CK‑M subunit,

LREFWürzburg U, Hennrich N, Lang H, et al. Determination of creatine kinase-MB in serum using inhibiting antibodies. Klin Wschr 1976;54(8):357-360.
the CK‑B activity is determined with a standardized method for the determination of CK with activation by NAC as recommended by the German Society for Clinical Chemistry (DGKC)
LREFBergmeyer HU, Breuer H, Büttner H, et al. Empfehlungen der Deutschen Gesellschaft für Klinische Chemie. Standard-Methode zur Bestimmung der Aktivität der Creatin-Kinase. J Clin Chem Clin Biochem 1977;15:249-254.
and the International Federation of Clinical Chemistry (IFCC)
LREFHørder M, Elser RC, Gerhardt W, et al. IFCC methods for the measurement of catalytic concentration of enzymes. Provisional recommendation IFCC method for creatine kinase Appendix A. J Int Fed Clin Chem 1990;2:26-35.
,
LREFSchumann G, Bonora R, Ceriotti F, et al. IFCC Primary Reference Procedures for the Measurement of Catalytic Activity Concentrations of Enzymes at 37 °C – Part 2. Reference Procedure for the Measurement of Catalytic Concentration of Creatine Kinase. Clin Chem Lab Med 2002;40(6):635-642.
in 1977 and 2002 respectively. This assay meets the recommendations of the IFCC and DGKC, but was optimized for performance and stability.

", "Language": "en" }, { "Name": "Reagents", "Value": "

Reagents - working solutions

R1

Imidazole buffer: 123 mmol/L, pH 6.5 (37 °C); EDTA: 2.46 mmol/L; Mg2+: 12.3 mmol/L; ADP: 2.46 mmol/L; AMP: 6.14 mmol/L; diadenosine pentaphosphate: 19 µmol/L; NADP (yeast): 2.46 mmol/L; N‑acetylcysteine: 24.6 mmol/L; HK (yeast): ≥ 36.7 µkat/L; G6P‑DH (E. coli): ≥ 23.4