Title: Therapeutic efficiency of tirofiban in acute coronary syndromes
Abstract: Christopher Heeschen and colleagues (Nov 20, p 1757)1Heeschen C Hamm CW Goldmann B Deu A Langenbrink L White HD Troponin concentrations for stratification of patients with acute coronary syndromes in relation to therapeutic efficiency of tirofiban..Lancet. 1999; 354: 1757-1762Summary Full Text Full Text PDF PubMed Scopus (488) Google Scholar describe the role of cardiac tropinin (cTn) I and T in the diagnosis and risk stratification of patients with acute coronary syndromes. cTnI values of more than 1.0 μg/L were associated with an increased risk of cardiac events and identified those patients likely to benefit from tirofiban. However, the method to determine cTnI and the diagnostic threshold for cTnI of 1.0 μg/L used may have caused flaws in the study. Intermethod differences in serum cTnI determination exist and there is no clear standardisation of cTnI immunoassays.2Donnelly R Millar-Craig MW Cardiac tropinins: IT upgrade for the heart..Lancet. 1998; 351: 537-538Summary Full Text Full Text PDF PubMed Scopus (44) Google Scholar, 3Apple FS Clinical and analytical standardization issues confroting cardiac tropinin I..Clin Chem. 1999; 45: 18-20PubMed Google Scholar Of particular concern is the propensity for false positive values of more than 1.0 μg/L by the AxSYM (Abbot Diagnostics, Abbott Park, IL USA) cTnI method used in this study. We found a false positive cTnI result measured on an AxSYM analyser. The patient was a white woman aged 70 years who was receiving cisplatin for small-cell carcinoma of the lung (patient 1; table). cTnI concentrations ranged between 242 μg/L and 766 μg/L on serial measurements. However, the total creatine kinase (CK) and CK-MB concentrations were normal and cTnT undetectable, as was cTnI by two other methods (ACS 180, Bayer Diagnostics, Tarrytown, NY, USA; Immulite 1, Diagnostic Products Corporation, LA, USA). There was no clinical or electrocardiographic evidence of cardiac involvement. Her rheumatoid factor was undectable, and immunoglobulin concentrations were normal.TableEffect of heterophilic antibodies and rheumatoid factor on cTnl concentrationPatient1234Reference limitRheumatoid factor<305060690<30 kU/LCTnl (AxSYM) old7664·43·83·8<2·0μg/LcTnI (AxSYM) new1·60·61·30·3<2·0μg/L Open table in a new tab We suspected that the patient had heterophilic antibodies,4Fitzmaurice TF Brown C Rifai N Wu AHB Yeo KJ False increase of cardiac tropinin I with heterophilic antibodies..Clin Chem. 1998; 44: 2212-2214PubMed Google Scholar although she had no history of exposure to animal proteins. Neither mouse nor goat serum had any effect on the measured concentrations of cTnI. Preincubation of the patient's serum with AxSYM CK-MB reagent containing goat serum reduced the measured cTnI concentration from 242 μg/L to 6.5 μg/L) of its pretreatment concentration. Incubation with protein-A removed the interference such that the cTnI concentration was less than 1.0 μg/L. Patients with a positive rheumatoid factor may also have falsely increased cTnI concentrations by the AxSYM cTnI method.5Dasgupta A Banerjee SK Datta P False positive tropinin I in the MEIA due to the presence of rheumatoid factors in serum. Elimination of this interference by using a polyclonal antisera agairist rheumatoid factors..Am J Clin Pathol. 1999; 112: 753-756PubMed Google Scholar We showed that three of 17 patients with a positive rheumatoid factor had cTnI concentrations of more than 1.0 μg/L by this method (patients 2–4; table). Because of both these drawbacks, Abbott has recently reformulated the blocking reagents used in its AxSYM cTnI assay. The new formulation still results in cTnI concentrations of more than 1.0 μg/L for one of the three patients (table) with positive rheumatoid factor. Moreover, the patient with heterophilic antibodies returned a result of 1.6 μg/L. Taken together, the potential interferences by heterophilic antibodies and rheumatoid factor with the AxSYM cTnI method suggest that the diagnostic threshold of 1.0 μg/L used by Heeschen and colleagues may result in some patients with falsely raised cTnI concentrations being wrongly classfied as at increased risk for cardiac events and unnecessarily treated with tirofiban. The propensity of this method for false positive cTnI concentrations may impact on risk calculations. Therapeutic efficiency of tirofiban in acute coronary syndromesAuthors' reply Full-Text PDF