Troponin - Non-MI Causes of Troponin Elevation

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number of studies. 34,38–41 The incidence of thisinterference varies considerably in the literature,40–43 ranging from 0.17 to 40%. Various sourceshave been proposed to give rise to heterophilicantibodies, and these include the use of mousemonoclonal antibodies in diagnostic imaging andcancer therapy, 44 exposure to microbial antigens, 39,45exposure to foreign animal proteins, 41 and autoimmunediseases such as rheumatoid arthritis. 38,40Recognizing the significance of this interferenceby heterophilic antibodies, the manufacturers recommendusing the antibody blocking agents alongwith their cardiac troponin immunoassays wheneverthis interference is suspected. 46–47 However, theresults of these blocking agents are not very convincing.34,37,48–53 Therefore, it is important that themanufacturers continue to improve their assays. Inthis regard, Kim et al 43 evaluated the performance ofthe revised Dimension cardiac TnI assay (DadeBehring; Deerfield, IL). They found that the revisedDimension cardiac TnI assay removed the interferencein most of the samples with which the originalDimension cardiac TnI assay had given falsely elevatedlevels, and greatly decreased the interferencein the remaining samples.Rheumatoid factor is another cause of interferencein the immunoassays. It has been reported that5% of healthy patients might have circulating rheumatoidfactor, and approximately 1% of patients withelevated cardiac TnI levels may have this elevationsolely because of the rheumatoid factor. 54 When thisscenario is suspected, a rheumatoid factor-blockingagent can be used. 38Excess fibrin is another well-reported source offalsely elevated cardiac TnI levels. 36 Roberts et al 55observed that incompletely clotted specimencontributed to the false elevations in cardiac TnIlevels with the Stratus II batch analyzer (DadeInternational). The manufacturers mention this possibilityin the package insert and advise care with thespecimens from patients receiving anticoagulanttherapy. The investigators found three approaches tobe useful to correct this interference: (1) heparinizingthe tubes before analysis, (2) removing excessfibrin by repeating the centrifugation, and (3) addingSuperSerum (TTC; Edison, NJ), which containsprotamine sulfate, thrombin, and snake venom toenhance coagulation.In addition, Roberts et al 55 found that some of theinterference due to free fibrin and microparticles canbe avoided with repeat centrifugation of the sampleand/or the use of a clot activator. However, Beyne etal, 56 in an open comparative study, found that asingle centrifugation of collection tubes containingthrombin as a clot activator is not enough to avoidfalse-positive cardiac TnI results on the ACCESSanalyzer (Beckman Coulter; Fullerton, CA).Finally, malfunction of the analyzer itself is anotherreported cause of false elevations in cardiacTnI results. Galambos et al 37 reported several casesof falsely elevated plasma cardiac TnI levels due to atemporary malfunction of the AxSYM analyzer (AbbottLaboratories; Abbott Park, IL). The operationmanual provided by the manufacturer mentions thepossibility of a solution dispenser misalignment ifthe dispensers are repositioned incorrectly duringthe weekly maintenance. 57 The authors recommendrunning quality-control samples after each maintenanceof the analyzer.ConclusionsCardiac troponin can be elevated in a variety ofconditions other than acute MI. Therefore, an accuratediagnosis in a patient with elevated troponinrelies heavily on the clinical information in thatparticular case. Increased levels of troponin in theseconditions generally provide significant prognosticinformation. Knowledge about the incidence, clinicalcorrelation, and clinical significance of increasedtroponin in these conditions are important in thecurrent era of widespread and indiscriminate testingof troponin in clinical practice.References1 A Jaffe AS, Ravkilde J, Roberts R, et al. It’s time for a changeto a troponin standard. Circulation 2000; 102:1216–12202 Antman EM, Tanasijevic MJ, Thompson B, et al. Cardiacspecifictroponin I levels to predict the risk of mortality inpatients with acute coronary syndromes. N Engl J Med 1996;335:1342–13493 Myocardial infarction redefined: a consensus document of theJoint European Society of Cardiology/American College ofCardiology Committee for the redefinition of myocardialinfarction. J Am Coll Cardiol 2000; 36:959–9694 Fleming SM, O’Byrne L, Finn J, et al. False-positive cardiactroponin I in a routine clinical population. Am J Cardiol 2002;89:1212–12155 Kim WJ, Laterza OF, Hock KG, et al. Performance of arevised cardiac troponin method that minimizes interference’sfrom heterophilic antibodies. Clin Chem 2002; 48:1028–10346 Karjalainen J, Heikkila J. Acute pericarditis: myocardial enzymerelease as evidence for myocarditis. Am Heart J 1986;111:546–5527 Brandt RR, Filzmanier K, Hanrath P. Circulating cardiactroponin I in acute pericarditis. Am J Cardiol 2001; 81:1326–13288 Bonnefoy E, Gordon P, Kirkorian G, et al. Serum cardiactroponin I and ST-segment elevation in patients with acutepericarditis. Eur Heart J 2000; 21:832–8369 Goldhaber SZ, Visani L, De Rosa M, for ICOPER. Acutepulmonary embolism: clinical outcomes in the International1882 Reviews
Cooperative Pulmonary Embolism Registry (ICOPER). Lancet1999; 353:1386–138910 Ribeiro A, Lindmarker P, Juhlin-Dannfelt A, et al. EchocardiographyDoppler in pulmonary embolism: right ventriculardysfunction as a predictor of mortality. Am Heart J 1997;95:67–6811 Como-Canella I, Gamello C, Martinez-Onsurbe O, et al.Acute right ventricular infarction secondary to a massivepulmonary thromboembolism. Eur Heart J 1988; 9:534–54012 Adams JE III, Seigel BA, Goldstein JA, et al. Elevation ofCK-MB following pulmonary embolism: a manifestation ofoccult right ventricular infarction [letter]. Chest 1994; 105:161713 Giannitis E, Muller-Bardorff M, Volkhard K, et al. Independentprognostic value of cardiac troponin T in patients withconfirmed pulmonary embolism. Circulation 2000; 102:211–21714 Goldhaber SZ. Treatment of acute pulmonary embolism. In:Braunwald E, Goldhaber SZ, eds. Atlas of heart disease.Vol 3. Cardiopulmonary diseases and cardiac tumors. Philadelphia,PA: Current Medicine, 199515 Douketis JD, Crowther MA, Stanton EB, et al. Elevatedcardiac troponin levels in patients with subacute pulmonaryembolism. Arch Intern Med 2002; 162:79–8116 Muller R, Gould L, Betzu R, et al. Painless myocardialinfarction in the elderly. Am Heart J 1990; 119:202–20417 Missov E, Calzolari C, Pau B. Circulating cardiac troponin Iin severe congestive heart failure. Circulation 1997; 96:2953–295818 La Vecchia L, Mezzena G, Ometto R, et al. Detectable serumtroponin I in patients with heart failure nonmyocardial ischemicorigin. Am J Cardiol 1997; 80:88–9019 Missov E, Mair J. A novel biochemical approach to congestiveheart failure: cardiac troponin T. Am Heart J 1999; 138:95–9920 Setsuda K, Seino Y, Takahashi N, et al. Clinical significance ofelevated levels of cardiac troponin T in patients with chronicheart failure. Am J Cardiol 1999; 84:608–61121 Perna ER, Macin SM, Parras JI, et al. Cardiac troponin Tlevels are associated with poor short- and long-term prognosisin patients with acute cardiogenic pulmonary edema. AmHeart J 2002; 143:814–82022 Guler N, Bilge M, Eryonucu B, et al. Cardiac troponin Ilevels in patients with left heart failure and cor pulmonale.Angiology 2001; 52:317–32223 Cummins B, Auckland ML, Cummins P. Cardiac-specifictroponin-I radioimmunoassay in the diagnosis of acute myocardialinfarction. Am Heart J 1987; 113:1333–134424 Smith SC, Ladenson JH, Mason JW, et al. Elevations ofcardiac troponin I associated with myocarditis, experimentaland clinical correlates. Circulation 1997; 95:163–16825 Ammann P, Fehr T, Minder EI, et al. Elevation of troponinI in sepsis and septic shock. Intensive Care Med 2001;27:965–96926 ver Elst KM, Spapen HD, Nguyen DN, et al. Cardiactroponins I and T are biological markers of left ventriculardysfunction in septic shock. Clin Chem 2000; 46:650–65727 Arlati S, Brenna S, Prencipe L, et al. Myocardial necrosis inICU patients with acute non-cardiac disease: a prospectivestudy. Intensive Care Med 2000; 26:31–3728 Spies C, Haude V, Fitzner R, et al. Serum cardiac troponin Tas a prognostic marker in early sepsis. Chest 1998; 113:1055–106329 Hinshaw LB. Sepsis/septic shock: participation of the microcirculation;an abbreviated review. Crit Care Med 1996;24:1072–107830 Kollef MH, Ladenson JH, Eisenberg PR. Clinically recognizedcardiac dysfunction: an independent determinant ofmortality among critically ill patients. Chest 1997; 111:1340–134731 Hamm CW, Giannitsis E, Katus HA. Cardiac troponin elevationsin patients without acute coronary syndrome. Circulation2002; 106:2871–287232 Guest TM, Ramantham AV, Tuteur PG, et al. Myocardialinjury in critically ill patients: a frequently unrecognizedcomplication. JAMA 1995; 273:1945–194933 Bodor GS, Porterfield D, Voss EM, et al. Cardiac troponin Iis not expressed in fetal and healthy or diseased adult humanskeletal muscle tissue. Clin Chem 1995; 41:1710–171534 Fitzmaurice TF, Brown C, Rifai N, et al. False increase ofcardiac troponin I with heterophilic antibodies. Clin Chem1998; 44:2212–221435 Schifman RB, James SH, Sadrzadeh SMH, et al. Betweenassayvariation in false positive troponin I measurements inpatients on renal dialysis or with positive rheumatoid factor[abstract]. Clin Chem 1999; 45:A14536 Nosanchuk JS. False increases of troponin I attributable toincomplete separation of serum [letter]. Clin Chem 1999;45:71437 Galambos C, Brink DS, Ritter D, et al. False-positive plasmatroponin I with the AxSYM analyzer. Clin Chem 2000;46:1014–101538 Dasgupta A, Banjiree SK, Datta P. False positive troponin I inthe MEIA due to the presence of rheumatoid factors inserum. Am J Clin Pathol 1999; 112:753–75639 Covinsky M, Laterza O, Pfeifer JD, et al. An IgM antibody toEscherichia coli produces false-positive results in multipleimmunometric assays. Clin Chem 2000; 46:1157–116140 Boscato LM, Stuart MC. Incidence and specificity of interferencein two-site immunoassays. Clin Chem 1986; 32:1491–149541 Kricka LJ. Human anti-animal antibody interference in immunologicassays. Clin Chem 1999; 45:942–95642 Thompson RJ, Jackson AP, Langlios N. Circulating antibodiesto mouse monoclonal immunoglobulins in normal subjects:incidence, species specificity, and effects on a two-site assayfor creatine kinase-MB isoenzyme. Clin Chem 1986; 32:476–48143 Kim WJ, Lazerta OF, Hock KG, et al. Performance of arevised cardiac troponin method that minimizes interferencesfrom heterophilic antibodies. Clin Chem 2002; 48:1028–103444 Carey G, Lisi PJ, Schroeder TJ. The incidence of antibodyformation to OKT3 consequent to its use in organ transplantation.Transplantation 1995; 60:151–15845 Posnet DN, Edinger J. When do microbes stimulate rheumatoidfactor? J Exp Med 1997; 185:1721–172346 Vaidya HC, Beatty GB. Eliminating interference from heterophilicantibodies in a two-site immunoassay for creatininekinase MB by using Fab conjugate and polyclonal mouse IgG.Clin Chem 1992; 38:1737–174247 Yeo KT, Storm CA, Li Y, et al. Performance of the enhancedAbbott AxSYM cardiac troponin I reagent in patients withheterophilic antibodies. Clin Chim Acta 2000; 292:13–2348 Turpeinen U, Lehtovirta P, Stenman UH. CA125 determinedby three methods in samples from patients with humananti-mouse antibodies (HAMA). Clin Chem 1995; 41:1667–166949 Cole LA, Rinne KM, Shahabi S, et al. False positive hCGassay result leading to unnecessary surgery and chemotherapyand needless occurrences of diabetes and coma. Clin Chem1999; 45:313–31450 Sosolik RC, Hitchcock CL, Becker WJ. Heterophilic antibodiesproduce spuriously elevated concentrations of the MBisoenzyme of creatine kinase in a selected patient population.Am J Clin Pathol 1997; 107:506–510www.chestjournal.org CHEST / 125 /5/MAY, 2004 1883
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Troponin - Non-MI Causes of Troponin Elevation

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