title: Quality specifications for biochemical markers of myocardial injury.
abstract: BACKGROUND
  The current approach to the diagnosis and monitoring of myocardial damage, recognizes to biochemical markers, and in particular to troponins, a key role being well demonstrated that all elevated values were associated with a worsened prognosis. In 2001, the IFCC Committee on Standardization of Markers of Cardiac Damage published guidelines addressing the quality specifications for troponin assays in order to guarantee an analytical performance satisfying medical requirements and to standardize the quality of commercial methods. We describe how the application of quality specifications may be useful in daily practice, in order to provide advice to clinicians in the investigations of complex clinical cases of patients suffering from myocardial damage.
  
  
  METHODS
  The samples from three patients (cases 1-3) admitted to the hospital with symptoms suggestive of cardiac disease, showing high troponin I (cTnI) values not correlated with clinical condition, were investigated in order to verify the accuracy of the laboratory data. The standard of quality specifications related to assay specificity, imprecision and interferences were evaluated using different platforms for cTnI assays, carrying out imprecision profile and specific studies on more common interferents in immunoassays.
  
  
  RESULTS
  The obtained results allow us to demonstrate two cases of false-positive cTnI values attributable to a macrocomplex between a modified "in vivo" cTnI and immunoglobulin G (case 1) and to a presence of heterophilic antibodies affecting the RxL Dimension procedure (case 3). Instead, the accuracy of data obtained in case 2 was evidenced by the imprecision profile obtained in our laboratory and by the comparison of results between different laboratories using same platform.
  
  
  CONCLUSIONS
  The lack of standardization as well as the wide differences in the development of each assay give rise to major concerns regarding cTnI determinations. The laboratory must therefore check the compliance between the analytical characteristics of the method utilised against recommended quality specifications for a reliable understanding of the frequency of false-positive results as well as other serious analytical errors.
authors.affiliation: Department of Laboratory Medicine, Chief, University-Hospital of Padova, Azienda Ospedaliera di Padova, Via Giustiniani, 2, Padova 35128, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Zaninotto
authors.forename: M
authors.initials: M
authors.lastname: Mion
authors.forename: S
authors.initials: S
authors.lastname: Altinier
authors.forename: M
authors.initials: M
authors.lastname: Forni
authors.forename: M
authors.initials: M
authors.lastname: Plebani
mesh_terms: D000328:Adult; D000368:Aged; D000910:Antibodies, Heterophile / Q000097:blood; D000918:Antibody Specificity; D015415:Biomarkers / Q000097:blood*; D009202:Cardiomyopathies / Q000097:blood / Q000175:diagnosis*; D016022:Case-Control Studies; D005189:False Positive Reactions; D005260:Female; D017408:Guidelines as Topic; D006801:Humans; D007118:Immunoassay; D011786:Quality Control; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019210:Troponin I / Q000097:blood; D020107:Troponin T / Q000097:blood
chemical_list: D000910:Antibodies, Heterophile; D015415:Biomarkers; D019210:Troponin I; D020107:Troponin T