You are on page 1of 12


Principle Principles of the procedures The Access AccuTnI assay is a two-site immunoenzymatic (“sandwich”) assay. A sample is .added to a reaction vessel along with monoclonal anti-cTnI antibody conjugated to alkaline phosphatase and paramagnetic particles coated with monoclonal anti-cTnI antibody. The human cTnI binds to the anti-cTnI antibody on the solid phase, while the anti-cTnI antibody - alkaline phosphatase conjugate reacts with different antigenic sites on the cTnI molecules. After incubation in a reaction vessel, materials bound to the solid phase are held in a magnetic field while unbound materials are washed away. Then, the chemiluminescent substrate Lumi-Phos* 530 is added to the vessel and light generated by the reaction is measured with a luminometer. The light production is directly proportional to the concentration of cTnI in the sample. The amount of analyte in the sample is determined from a stored, multi-point calibration curve. Summary and Explanation Coronary artery disease is not only a leading cause of death in men and women in the US, but is also associated with other life-threatening complications (1,2,3). The development of symptoms of coronary artery disease, which at times is unexpected and sudden, is associated with increased risk for adverse cardiac events such as death, myocardial infarction (MI), or hospitalization requiring urgent revascularization. Therefore, patients presenting with ischemic syndromes require prompt management. Specific and sensitive cardiac markers (troponin I and T) have been used in conjunction with other clinical findings and patient history information to better identify subjects with MI (1,2,4,5,6). These specific cardiac markers have also been used to identify those patients at higher risk for short- and long-term adverse cardiac events (endpoints/outcomes) (1,7,8,9,10). Cardiac troponin I is a contractile protein exclusively present in the cardiac muscle (11,12). It is one of three subunits of the troponin complex (I, T, C), which with tropomyosin are bound to actin in the thin filament of the myofibril. cTnI is found as free troponin I (free TnI) and complexed with troponin C (binary IC), with troponin T (binary IT) or with both troponin C and troponin T (ternary ITC). Its physiological role is to inhibit the ATPase activity of the actin-myosin complex in the absence of calcium, and therefore, to prevent muscular contraction (13). Three tissue isoforms have been identified: • • Fast troponin I and slow troponin I with molecular weights of 19,800 Da each, expressed in fast twitch and slow twitch skeletal muscle fibers, respectively. cTnI with a molecular weight of 24,000 Da contains an additional 31 amino acid residues in the Nterminal.

Sequencing of cTnI from mammals has shown important differences between the cardiac (14) and skeletal (15) forms. All three troponin I isoforms are encoded by different genes. The human cTnI exhibits only 52% and 54% amino acid sequence homology with the human fast and slow skeletal troponin I, respectively. The Access AccuTnI monoclonal antibody pair is selected to be cTnI specific. In addition, it has been well documented that skeletal muscle does not express cTnI, either during development or in response to stimuli (16). Therefore, the absolute cardiospecificity of cTnI allows distinction between cardiac and skeletal injuries, and allows diagnosis of myocardial infarction distinct from muscle lesions (rhabdomyolysis, polytraumatism) and non-cardiac surgery (16,17,18,19). Elevated troponin I levels have also been documented in cases of unstable angina (UA) (20) and congestive heart failure (CHF) (21).

or other major cardiac complications requiring hospitalization and potentially urgent revascularization (UR). and storing blood 1. The development and commercialization of the more specific and sensitive cardiac troponin I (cTnI) immunoassays have significantly contributed to the diagnosis of MI and to the risk stratification of patients with NSTEMI/UA.13): recommendations for handling.and under-estimation of the true concentration of troponin I in a complex biological milieu. transfer at least 500 μL of cell-free sample . 3. while other assays demonstrate a substantial difference. The Access AccuTnI assay recognizes the binary troponin IC or IT or ternary troponin ITC complexes and free cTnI equally. The 2000/2002 American College of Cardiology (ACC) and the American Heart Association (AHA) Guideline Update for the management of these patients strongly recommends to include cTnI measurements for the risk stratification of patients presenting with symptoms suggestive of acute coronary syndromes (2. processing. allows an unbiased determination of the total cTnI present in samples from the same subject over the course of AMI. For some assays.6). the assessment of the prognosis will be useful in both selecting the site of care and in identifying patients most likely to benefit from specific therapeutic interventions. Troponin I levels peak at approximately 12-16 hours and can remain elevated for 4-9 days post-AMI.34). Keep tubes stoppered at all times. cTnI is 13 times more abundant in the myocardium than CK-MB and does not normally circulate in the blood. an assessment of the prognosis should assist physicians in identifying and managing high risk patients. the relative responses to the various forms of cTnI are nearly equal.29).31).24. Equimolar binding.25). defined as the ability to recognize both the complexed and free cTnI forms equally. These same studies noted that the time to peak concentration of cTnI occurred later in patients who did not receive thrombolytic therapy (17.33. In light of the potential adverse outcomes faced by these patients such as cardiac death or nonfatal ischemic events. In addition. Substantial degradation occurs both invivo and in-vitro. The pattern of release of these forms over the course of AMI is still under investigation. 2.28. the assay responds to both the phosphorylated and dephosphorylated forms of cTnI complex equally (32). Allow serum samples to clot completely before centrifugation. The 2002 ACC and the European Society of Cardiology (ESC) guidelines recommend that individual laboratories define their own reference range and that an elevated value of cTnI be defined as a measurement above the 99th percentile of a normal control group (i. it has been reported that it is difficult to predict who will suffer an adverse event in those patients with UA and without evidence of ST segment elevation (NSTEMI) (1). The collection of at least three blood samples during the early triage period has been recommended (22). so the signal to noise ratio is more favorable for the detection of myocardial necrosis (23). The differential recognition of complexed and free cTnI forms is common for many commercial methods (26. B. The latter may lead to over. the 99th percentile upper reference limit) (4.cTnI levels in acute myocardial infarction (AMI) exhibit similar rise and fall patterns to those found in CKMB. MI. binary IT complex and free cTnI (26. If not analyzed within two hours after centrifugation. Cumulative data from several studies indicate troponin I levels are detectable (above quoted values for non-AMI samples) 3-6 hours after the onset of chest pain. The Access AccuTnI assay utilizes monoclonal antibodies directed against the more stable region of the molecule. Recent studies have shown that the predominant cTnI form present in blood of patients after AMI is the binary troponin IC complex with smaller amounts of the ternary ITC complex. The C-terminal of the molecule is preferentially cleaved then followed by the cleavage of the N-terminal (27.e. Observe the following samples (12. However. and is therefore less affected by degradation of cTnI. Specimen Collection A.5).30. Collect all blood samples observing routine precautions for venipuncture. cTnI is highly susceptible to proteolysis and enzymatic modification. Serum and plasma (heparin) are the recommended samples. Ultimately.27. Unstable angina comprises a broad spectrum of patients with varying levels of risk for suffering an adverse event such as death. 4.

or calibration curve. discard the pack. with surfactant. BSA matrix. protein (bovine. refrigerate the samples at 2 to 8°C. R1b: 0. is used to convert RLU (Relative Light Unit) measurements of patient samples to specific quantitative analyte concentrations. R1c: Mouse monoclonal anti-human cTnI alkaline phosphatase conjugate diluted in ACES buffered saline. Stable at 2 to 10°C for 56 days after initial use. 6.1% sodium azide. mouse). 50 tests/pack. Refrigerate at 2 to 10°C for a minimum of two hours before use on the instrument.1% ProClin** 300. 2. assay calibrators) are tested like patient samples to measure the response. freeze at -20°C or colder. Access AccuTnI Calibrators Cat. broken elastomer). 1. No. Provided ready to use. Tightly stopper the tube immediately. with surfactant. 1 mL/vial Quantitative assay calibration is the process by which samples with known analyte concentrations (i. Signs of possible deterioration are a broken elastomeric layer on the pack or control values out of range. Store upright and refrigerate at 2 to 10°C.e. Stable until the expiration date stated on the label when stored at 2 to 10°C. 3. a storage tube. Thaw samples only once. Store samples tightly stoppered at room temperature (15 to 30°C) for no longer than eight hours. Fullerton. This mathematical relationship.1 N NaOH. Reagents and Equipment Beckman Coulter. 5. C. < 0.. 2. 4300 N. bovine serum albumin (BSA) matrix. . and 0. If the reagent pack is damaged (i. If the assay will not be completed within 48 hours. 8.25% ProClin 300. R1: Access AccuTnI Reagent Pack Cat. goat. R1a: Paramagnetic particles coated with mouse monoclonal anti-human cardiac troponin I (cTnI) suspended in TRIS buffered saline. Harbor Blvd. 7. Ensure residual fibrin and cellular matter has been removed prior to analysis.e. Use the following guidelines when preparing specimens. unless instructed otherwise in the product insert: 1. 33345: S0-S5. If the assay will not be completed within eight hours.1% sodium azide.. Follow blood collection tube manufacturer’s recommendations for centrifugation. CA 92835 A. 33340: 100 determinations. The mathematical relationship between the measured responses and the known analyte concentrations establishes the calibration curve. or for shipment of samples. No. and 0. B. < 0. 2 packs.

Freeze upon receipt at -20°C or colder. Stable until the expiration date stated on the label when stored at room temperature (15 to 30°C). After initial use.1% ProClin** 300. Refer to the appropriate system manuals and/or Help system detailed instructions. 25 and 100 ng/mL (µg/L) in buffered BSA matrix with surfactant. Calibration Card: 1 C.0. 1. and reviewing calibration data. Return calibrators to 2 to 10°C after each use. R3 Wash Buffer: TRIS buffered saline. 2. Condition Unopened Storage 2 to 8°C Stability Until expiration date stated on the label Minimum 18 hours Maximum 14 days Maximum 5 days Equilibration prior to use (unopened) In use (opened) 15 to 30°C (room temperature) Internal substrate supply position External fluids tray substrate position In use (opened) Maximum 14 days R2 Substrate: Lumi-Phos 530 (buffered solution containing dioxetane Lumigen* PPD. configuring calibrators. surfactant. Quality Control (QC) materials: commercial control material. An increase in substrate background measurements or increased relative light units for the zero calibrators in “sandwich”-type assays may indicate instability. the thawed vials are stable at 2 to 10°C for 60 days. < 0. .1% ProClin 300.1% sodium azide. Label the vials with the date of thaw and the date of expiration. < 0. No. 3. S0: Buffered bovine serum albumin (BSA) matrix with surfactant < 0.1% ProClin 300. Stable until the expiration date stated on the label when stored at -20°C or colder. Refer to the following chart for storage conditions and stability. Signs of possible deterioration are control values out of range. and 0. Avoid bubble formation. Refer to the appropriate system manuals and/or Help system detailed instructions. Do not refreeze opened vials.2.Provided ready to use. fluorescer. 81906: 4 x 130 mL Provided ready to use. Access Substrate Cat. Refer to the appropriate system manuals and/or Help system for information on calibration theory. 8547197: 1 X 10 L (UniCel™Dxl) Provided ready to use. D. calibrator test request entry. 5. An increase in substrate background measurements may indicate instability.1 sodium azide. and surfactant). Access Wash Buffer Cat. E.3. 1. Mix contents thoroughly by gently inverting before use.1% sodium azide. and 0. and 0. No. Refer to calibration card and/or vial labels for exact concentrations. S1–S5: Recombinant troponin complex at cTnI levels of approximately 0.

Xi. Mix gently by inverting before use. Samples can be accurately measured within the analytic range of the lower limit of detection and the highest calibrator value of the specific assay. and reviewing calibration data. S 28-37: After contact with skin. Refer to the appropriate system manuals and/or Help system for instructions on how to enter a sample dilution in a test request. configuring calibrators.1% sodium azide. or prior certification.F. The Material Safety Data Sheet (MSDS) is available upon request. However. Do not pool bottles of substrate. 0. treatment. Stable until the expiration date stated on the vial label when stored at 2 to 10°C. For the Access AccuTnI assay. Calibration Details Run the Access AccuTnI S0 and S1 Calibrators in quadruplicate. G. Access Sample Diluent A Cat. 5. Keep tightly closed at all times. Access Immunoassay System and supplies Warnings and Precautions 1. Store and dispose of these materials and their containers in accordance with local regulations and guidelines. < 0. 6. Provided ready to use.5% ProClin 300. flush with a large volume of water to prevent azide build-up (36).5% ProClin 300. calibrator test request entry. Sodium azide may react with lead and copper plumbing to form highly explosive metal azides. If a sample contains more analyte than the stated value of the S5 calibrator. If a quantitative value is required. dilute the sample following dilution instructions in the specific assay labeling under “Limitations of the Procedure” in the reagent pack section. No. Allow the contents to stand for 10 minutes at room temperature. On disposal of liquids. and the S2–S5 Calibrators in duplicate. 81908: 4 mL/vial The analyte level in patient samples may exceed the level of the specific S5 calibrator. Refer to the appropriate system manuals and/or Help system for information on calibration theory. Use an appropriate disinfectant for decontamination. 4. wash immediately with plenty of soap and water. Substrate is sensitive to air exposure. handle these products as potentially infectious according to universal precautions and good clinical laboratory practices. Wear suitable gloves. 2. An active calibration curve is required for all tests. H. regardless of their origin. . R 43: May cause sensitization by skin contact. Patient samples and blood-derived products may be routinely processed with minimum risk using the procedure described. it will be necessary to dilute the samples in order to determine the analyte concentration. Irritant: 0. Access Sample Diluent A: Buffered BSA matrix with surfactant. calibration is required every 56 days. For in vitro diagnostic use. Avoid bubble formation. 3.

quality control materials are analyzed in each 24-hour time period. B. Quality Control Quality control materials simulate the characteristics of patient samples and are essential for monitoring the system performance of immunochemical assays. BioRad Liquichek Cardiac Markers Control Level 1 BioRad Liquichek Cardiac Markers Control Level 2 Un-opened: Until expiration date stored at -20 to -70 ºC. Procedure A. Access Instrument Refer to the UniCel DxI 800 Operators and Reference manuals and/or Help system for preparation and operation. . and reviewing test results. configuring tests. Serum Thawed: 10 days at 2-8 ºC.Sample Manager and/or Help system for information on managing samples. Serum Thawed: 10 days at 2-8 ºC. QUALITY CONTROL MATERIAL CONTROL NAME SAMPLE TYPE STORAGE Un-opened: Until expiration date stored at -20 to -70 ºC.The Access AccuTnI Calibrators are provided at six levels . Because samples can be processed at any time in a “random access” format rather than a “batch” format.(10).2. Serum Thawed: 10 days at 2-8 ºC. The following controls should be prepared and used in accordance with the package and approximately 0. Section 3 . 5. Assay Procedure Refer to the UniCel DxI 800 Operators manual. Discrepant quality control results should be evaluated and handled as described in the QUALITY CONTROL PROCEDURES section of the Core Laboratory General Procedures manual. BioRad Liquichek Cardiac Markers Control Level 3 Un-opened: Until expiration date stored at -20 to -70 ºC. 25 and 100 ng/mL. requesting tests. 1. Copies of these inserts can be found in the QUALITY CONTROL PROCEDURE (General) section of the Core Laboratory General Procedures manual. Assay calibration data are valid up to 56 days.0.3.

from the medians of nine determinations (32).5. The amount of analyte in the sample is determined from the measured light production by means of the stored calibration data.02–0. Clinical studies have documented these conditions to include stable or unstable angina pectoris. Any condition resulting in myocardial injury can potentially elevate cTnI levels above the expected normal range. After a myocardial infarction.03 ng/mL (95% CI at this concentration is 0.04 ng/mL was determined to be 20 and 14%. 4. and cardiac surgery or invasive testing (4. Refer to the appropriate system manuals and/or Help system for complete instructions on reviewing sample results. cTnI concentrations are detectable 3-6 hours after the onset of chest pain. Patient test results can be reviewed using the appropriate screen. myocarditis.16.5th and 99th percentiles (upper reference limit) as determined using lithium heparin plasma samples for a population of apparently healthy adults with no known cardiac disease are shown in the following table: n 254 Age Range 19–88 97.05) Remove any fibrin and centrifuge the serum in a pour off tube for 10 minutes at 3000 rpm. Indicate the “original result. Myocardial infarction has been redefined by the National Academy of Clinical Biochemistry (NACB) and the Joint European Society of Cardiology (ESC)/American College of Cardiology (ACC) Committee (4.22). respun” as an internal comment (?) Note: The 95% confidence interval of a measurement of concentration at a level of the upper reference limit is calculated as ± two times the total %CV at the corresponding concentration.5th percentile 0.5.05 ng/mL AMI positive: >0. B.50 ng/ml. respectively. The total imprecision at 0.Results A. These organizations recommend the use of biochemical markers in conjunction with the 97. World Health Organization (WHO) (38) requires two of the following criteria for confirmation of AMI: evolutionary changes in the ECG or history of chest pain coupled with elevated cardiac enzymes. The 97. Patient test results are determined automatically by the system software using a weighted four parameter logistic curve (4PLC) math model. Expected Values Laboratory reference interval is <0. peak at approximately 12-16 hours.40).03 and 0. and can remain elevated for 4-9 days post-AMI.39.5th percentile (NACB) or 99th percentile (ESC/ACC) reference ranges to aid in the diagnosis of myocardial infarction and cardiac damage.04) 99th percentile 0. . (fibrin falsely elevates troponin results) Following this 2nd spin analyze the supernatant for Troponin I Report the 2nd result.04 ng/mL (95% CI at this concentration is 0. Results > 0.03–0. congestive heart failure. 5.50 ng/mL must be repeated before reporting as follows: • • • • 1. 2.

6. 5. enter "Y". 6. Procedural Comments A. Refer to the appropriate system manuals and/or Help system for the minimum sample volume required. Messages are entered with a question mark (?) in front of each line to avoid printing on the patient's report. A "V" will appear after the test. Press F12 to bring up the current date. operational limitations and precautions. Disregard other options below this field. The cursor moves to the Call area. Refer to the appropriate system manuals and/or Help system for a specific description of installation. coronary artery dissection. Following are the procedures for manual result entry: 1. hazards. Reporting Results The UniCel DxI 800 is interfaced with the Beckman Coulter DL2000 Datalink Manager which connects with the host LIS computer. All sample results that pass the established validation criteria are automatically verified by the DL2000 and the LIS and require no intervention by the technologist. Press F12 twice to return to the worklist. Refer to the Beckman Coulter DL 2000 Datalink Manager Procedure for further details. Mix contents of new (unpunctured) reagent packs by gently inverting pack several times before loading on the instrument.43).42. . The AMI cutoff value presented in the Clinical Performance section applies to heparin plasma and serum samples. A new screen opens up for documentation. Pertinent messages may be entered at this time (hemolyzed. and cocaine or amphetamine use may be responsible for acute ischemic syndrome potentially leading to cTnI levels above the reference range for healthy individuals (41. coronary embolism. 8. enter the order number(s) or it may be bypassed. 13. Use forty (40) µL of sample for each determination in addition to the sample sample container and system dead volumes. or press ENTER then F5 to review each order.) key. start-up. 3. 11. 2. Press F12 again to "Confirm modification to record? (Y/N)". Pend +Nonver (default) is displayed. and troubleshooting. 4. 9. The ENTER option will be highlighted. The diagnostic cut-off value above which a sample is considered positive for AMI using the Access AccuTnI assay was determined by ROC analysis (44). operating instructions. Manually enter the result if the result did not go across the interface and verify with the semicolon (. Move the cursor to "From order #"______To _____. 10.this option is used to correct or modify previously approved results. 8. Use the down arrow to advance to the required Order #. Press Enter key. Access the LIS system. B. Note: From order # always start with the current date. Non-atherosclerotic mechanisms such as arteritis. Select 3-Results and enter "V"-View/Enter results by Sel.Enter Y. 7. principles of operation. Document called results by simultaneously pressing the CTRL and "C" keys. etc). calibration procedures. Enter all information. Advance the cursor to the next area and enter the Template LX20. C. Do not invert open (punctured) packs. 7. maintenance. The cursor is now in the following area "Select tests by" TEMPLATE (default). Use the space bar to change to ALL . 12. See the Clinical Performance section for further information. Tests. lipemic. Press ENTER to advance the cursor to the STATUS area. system performance characteristics. using your ID and Password.

The Access AccuTnI results should be interpreted in light of the total clinical presentation of the patient. 500 mg/dL hemoglobin.D. 1000 mg/dL fibrinogen. refer to the appropriate system manuals and/or Help system. data from additional tests.01 ng/mL (µg/L). Each of the potential cross reactants was added to a lithium heparin plasma pool containing approximately 2 ng/mL purified cTnI complex and assayed in replicates of 10. Internal Laboratory linearity is 0. To manually convert concentrations to the International System. B. C. and the S2–S5 Calibrators in duplicate. E. may be present in patient samples. This study was based on NCCLS EP7-P (47).0 ng/mL.01 – 100.01–100 ng/mL (µg/L)]. To change sample reporting units to the International System of Units (SI units). E.004 -0. the possibility exists for interference by human anti-mouse antibodies (HAMA) in the sample. Run the Access AccuTnI S0 and S1 Calibrators in quadruplicate. such as human anti-goat antibodies.008 -0.001 -0. The following table describes the cross-reactivity of the assay with other myofibrillar proteins. If a sample contains more than > 100 ng/mL. • • If a sample contains less than the lower limit of detection for the assay.46) or in individuals who have been regularly exposed to animals. The system reports the results adjusted for the dilution.002 -0. clinical history. D. Samples can be accurately measured within the analytic range of the lower limit of detection and the highest calibrator value [approximately 0. The system default unit of measure for sample results is ng/mL. For assays employing mouse antibodies. 1000 mg/dL Triolein (triglycerides). or 6000 mg/dL of human serum albumin do not affect the concentration of cTnI assayed.001 -0.003 0. electrocardiogram (ECG). Additionally. Refer to the appropriate system manuals and/or Help system for instructions on entering a sample dilution in a test request. Samples containing up to 40 mg/dL bilirubin (conjugated). dilute one volume of sample with 9 volumes of Access Sample Diluent A. Human anti-mouse antibodies may be present in samples from patients who have received immunotherapy or diagnostic procedures utilizing monoclonal antibodies (45. report the results as less than that value < 0. clinical examination. Medical decisions should not be based on a single AccuTnI determination at one time point (22) . including: symptoms. Limitations of the Procedure A. µg/L. Substance Skeletal troponin I Cardiac troponin C Recombinant human cardiac troponin T Actin (rabbit) Myosin Tropomyosin (rabbit) Human CK-MB Myoglobin Analyte Added (ng/mL) 1000 1000 1000 1000 1000 1000 1000 1000 Cross-Reactivity (%) 0. other heterophile antibodies. and other appropriate information.034 -0. multiply ng/mL by multiplication factor 1.002 . All cTnI values obtained in the presence of each interferent were ± 10% of the control.

Califf RM. Heidenreich PA. Clin Chem 2000. De Lemos JA. 387078. **ProClin is a trademark of Rohm and Haas Company or its subsidiaries or affiliates. Am Heart J 2000. Fox KM. Access Substrate product insert. Hochman JS. 1. Theroux P. 139: 461-75. Alexander JC. Antman EM. Cardiac-speciÿc troponin I levels to predict the risk of mortality in patients with acute coronary syndromes. Wilcox RG. Wybenga DR. Tanasijevic MJ. Charlesworth A. Schaeffer JW. CA 92835. Pepine CJ. Berink P. N Engl J Med 1996. Dheitlin MD. Circulation 2000. Beasley JW. 3. CA 92835. SYNCHRON LX. Circulation 2000. Levin TN. Tanasijevic MJ. Fischer GA. Antman EM. . Inc. Steward DE. CA 92835. AccuTnI. Theroux P. Inc. McCabe CH.01 ng/mL (μg/L). ACC/AHA guidelines for the management recommendations. Fullerton. Tanasijevic MJ. 102: 149-156. 9.920 ng/mL (μg/L). Go A. Caspi A. McDonald KM. Pepine CJ. 36(3): 959-969. Braumwald E. 10. Thompson B. Cannon CP. Clin Cardiol 1999. Alpert JS. Kereiakes D. Antman EM. 2000. Jones RH. 22: 13-16. Inc. Guidelines for the diagnosis and management of unstable angina and non-Qwave myocardial infarction: Proposed revisions. Smith EE. Kupersmith J. Wybenga D. Kereiakes D. 8. Thompson C. 5. ACC/AHA guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial Infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients with Unstable Angina). Loper-Sendon J. AHRQ Publication No. Beckman Coulter. Skene A. Access AccuTnI product insert. Hlatky MA. 102(10): 1193-1209. JACC 2000. Cheitlin MD. Fullerton.A consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the Redeÿnition of Myocardial Infarction. Kupersmith J. 386966. European Heart Journal 2000. Access. Califf RM. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients with Unstable Angina). *Lumi-Phos and Lumigen are trademarks of Lumigen. Smith EE. G. Prediction of risk for patients with unstable angina. Beasley JW. Anders RJ. The lowest detectable level of cTnI distinguishable from zero (Access AccuTnI Calibrator S0) with 95% confidence is 0. Morrow DA. McCabe CH. 46(4): 453-460. and Braunmwald E. Fung AY. 335: 1342-1349. Access Wash Buffer product insert. The role of cardiac troponin-I (cTnI) in risk stratiÿcation of patients with unstable coronary artery disease. 2002. Clinical efÿcacy of three assays for cardiac troponin I for risk stratiÿcation in acute coronary syndromes: A thrombolysis in myocardial infarction (TIMI) IIB substudy. Schactman M. UniCel. Antman EM. Cannon CP. 21: 1502-1513. The Joint European Society of Cardiology/American College of Cardiology Committee. et al. Braunwald E. Steward DE. Inc. 01-E001 December. Cannon CP.] 7.F. Hochman JS. Schaeffer JW. Beckman Coulter. Oral glycoprotein IIb/IIIa inhibition with orboÿban in patients with unstable coronary syndromes (OPUS-TIMI 16) trial. Antman EM. Melsop KA. Hagan V. Antman EM. Braunwald E. and the Beckman Coulter logo are trademarks of Beckman Coulter. 105459. Thygesen K. Number 31. Myocardial Infarction redeÿned—a consensus document of the Joint European Society of Cardiology/American College of Cardiology Committee for the Redeÿnition of Myocardial Infarction. Langer A. Fullerton. Inc. Myocardial infarction redefined . References Beckman Coulter. Rifai N. 4. Toman J. 6. Levin TN. Hastie T. Alloggiamento T. Jones RH. 2. The Access AccuTnI assay does not demonstrate any "hook" effect up to 1.

Grolleau R. Pettersson K. Schechtman KB. FEBS Lett 1990. Lovgren T. Pau B. Missov ED. Wade R. Biochem J 1978. Etievent JP. Mair J. 341: 838-839. 17. Dabhaden N. Ferrini D et al. 45: 213-222. McPherson PH. Davila-Roman VG. Bodar G. 40:1291-1295 24. van Vlies B. Lancet 1993. 43: 1379-1385. 25. Bakker AJ. Pulkki K. Dienstl F. 1999. Ladenson JH. 14. 15. De Marco T. Cardiac troponin I in the diagnosis of myocardial injury and infarction. Eddy R. Ambach E. Grand RJA. Clin Chem 1999. Clin Chem 1998. Pau B. Clinical Chemistry 1995. Ladenson JH. Tijssen JGP. 45(7): 1104-1121. Diensti F. Larue C. Adams JE. Buechler KF. Jesse RL et al. Esakova TV. Puschendorf B. Dienstl F. Troponin I from human skeletal and cardiac muscles. Determination of cardiac troponin I forms in the blood of patients with acute myocardial infarction and patients receiving crystalloid or cold blood cardioplegia. Chocron S. Chem. Genser N. Gibler B. Biochem Soc Trans 1979. Clin. The regulation of contractile activity in muscle. Degradation of human cardiac troponin I after myocardial infarction. Leclercq F. Bereznikova AV. Mair J. Trinquier S. 270: 57-61. 88: 101-106. Genomics 1990. Kedes L. Maier J. Dasgupta A. Mair J. 1978. Mair P. Circulation 1997. 27. 19. 22. Clinica Chimica Acta. Chem. Feng YJ. Wu HBA. 28: 105-111. Comparison of amino acid sequence of troponin I from different striated muscles. 26. Bertinchant JP. Bodor GS. Gusev NB. Wu AHB. Toubin G. Morandell D. 20. Clin. and cardiac troponins I and T for acute myocardial infarction. Prognostic influence of elevated values of cardiac troponin I in patients with unstable angina. creatine kinase isoform ratios. Perry SV. Vallins JW. cDNA sequence. 18. 284: 175–185. Comparison of immunoreactivity of five human cardiac troponin I assays toward free and complexed forms of the antigen: implications for assay discordance. Larue C. Foster K. Koelemay MJW. Calzolari C. Chem 1999. 7: 346-357. VuopioPulkki LM. Clin Chem 1993. et al. Puschendorf B. Wilkinson JM. Landt Y. Molecular cloning of human cardiac troponin I using polymerase chain reaction. Lechleitner P. et al. Characterization of cardiac troponin I forms in the blood of patients with acute myocardial infarction and comparison of assays for troponin T and I. creatine kinase MB mass. 1996. 28. Calzolari C. Delmez JA. Mair P. 12. Cardiac-specific immunoenzymometric assay of troponin I in the early phase of acute myocardial infarction. Apple FS.11. 16. National Academy of Clinical Biochemistry Standards of Laboratory Practice: Recommendations for the use of cardiac markers in cornary artery disease. 342: 1220-1222. Genser N. Puschendorf B. Larue C. Giuliani I. Troponin I is released in bloodstream of patients with acute myocardial infarction not in free form but as complex. Cummins P. tissue-specific expression and chromosomal mapping of the human slow-twitch skeletal muscle isoform of troponin I. . Lechleitner P. Adams III JE. Galvani M. Moore R. 41: 1266-1272. Gorgels JPMC. Smits R. Clin. et al. Haagen FDM. Acta. Failure of new biochemical markers to exclude acute myocardial infarction at admission. Cardiac troponin I: a marker with high specificity for cardiac injury. Nature 271: 31-35. 29. 30. Morandell D. 44: 1198-1208. Circulation 1993. Datta P. 21. Cardiac troponin I to diagnose myocardial injury (letter). Biochem 1998. 171: 251259. Brand NJ. Bertinchant JP. Apple FS. Apple FS. Clin Chem 1997. Perry V. Equivalent early sensitivities of myoglobin. Shows TB. Laprade M. Comparable detection of acute myocardial infarction by creatin kinase MB isoenzyme and cardiac troponin I. Jaffe AS. Katrukha AG. 7: 593-617. Lechleitner P. Appl. Clinical insights on the use of highly sensitive cardiac troponin assays. Clin Chem 1999. Morjana NA. 23. 1994. 39: 972-979. Lancet 1993. Granier C. Biotechnol. 13. 245: 19–38. Severina ME. Wagner I. Ottani F. 95: 2053–2059. 45: 2266-2269.

N13. Maek DB et al. 1976. Clin Chem 1999. 1986. 97: 1195-1206. JP Etievent. Olson MD. Laboratory Quality Management: QC & QA. Chance S. Clin Chem 2000. 37. H18-A2. 39. 45: 822-828. CDC-22. Fuster V. Receiver-Operating Characteristic (ROC) Plots: A fundamental Evaluation Tool in Clinical Medicine. Use of Cardiac Troponin I as a Marker of Perioperative Myocardial Ischemia. Acute coronary syndromes. Interference testing in clinical chemistry. 41. al. Mosby-2001 book 1996. Campbell G. Woodrum DL. 84: 9-20. In Braunwald E (ed). ASCP Press. 44. Diagnosing and managing unstable angina. Kricka. Wu AHB. Jevans AW. Impact of antibody specificity and calibration material on the measure of agreement between methods for cardiac troponin I. Circ Res 1999. Zweig MH. Approved Guideline – Procedures for the Handling and Processing of Blood Specimens. 38. 32. Theroux P. Interferences in Immunoassays – Still a Threat. Chem. 24: 1945–1949. Falk E. Journal of American Medical Association 1995. 47.31. McDonough JL. et. Pathology of acute coronary syndromes. Roberts S. Gorman EG. IL. Chan S. Clin Chem 2002. Clin Chem 2002. Multicenter evaluation of an automated assay for troponin I. April 30. Report of the Joint International Society and Federation of Cardiology/World Heath Organization Task Force on Standardization of Clinical Nomenclature. V6. 42. National Committee for Clinical Laboratory Standards. et. Circulation 1994. Venge P. Atlanta GA: Centers for Disease Control. 90: 613-622. 39. Darte C. Myocardial Injury in Critically Ill Patients. TM Guest. 1989. Uettwiller-Geiger D. 34. Clin. World Health Organization. Apple FS. Circulation 1998. 33. Van Eyk JE. 1999. Price C. Annual of Thorac Surgery 1995. al. Jones RH. St Louis. Decontamination of Laboratory Sink Drains to Remove Azide Salts. Manual Guide – Safety Management. Carey RN. Nomenclature and criteria for diagnosis of ischemic heart disease. 48(6): 869-76. Unstable angina and non-Q-Wave myocardial infarction.1-3. Braunwald E. 40. 59: 607-9. 273. 59: 1192-1194. Chicago. Lagugger R. Atlas of Heart Disaeses. National Committee for Clinical Standards. Cembrowski GS. 1993. Van Eyk JE. 35. Bjerner J.31. 43. EP7-P. Acute myocardial infarction and other acute ischaemic syndromes. . 45. Collier C. No. 46. 36. 48: 613–621. 46: 1037. 4: 561-577. et al. Troponin I degradation and covalent complex formation accompanies myocardial ischemia/reperfusion injury. L. Shak PK. Newman D. Arrell DK. Immunometric Assay Interference: Incidence and Prevention. Olabiran Y. Bedzyk WD. Extensive troponin I and T modification detected in serum from patients with acute myocardial infarction. 3. 102: 1221-1226. Circulation 1979. Atar D. Circulation 2000. Organ L.