1 How Does Contrast Media Affect Cardiac Markers 2 and Coagulation Tests ? Experimental Study 3

9 Background and objectives: The fact that the results of troponin and Nt-proBNP interfere from biotin 10 caused some commercial firms to update their measurement methods. In particular, the clinical 11 incompatibility of cardiac test results may affect the risk of morbidity and mortality. The aim of this 12 study is to investigate the interference effects of 7 different contrast agents on cardiac markers 13 (Troponin-I, Nt-proBNP, Mass CK-MB, CK, AST, LDH) and coagulation tests (PT, APTT). 14 Materials and Methods: Seven different contrast medias were added into control materials by using 15 interference protocol. Concentration of PT, APTT, CK, AST, LDH, Mass CK-MB, Troponin-I, 16 Nt-proBNP were measured by Sysmex CS-2100, Abbott c16000, Siemens Centaur XP and AFİAS-6 17 analyzer. The amount of deviations from target values were calculated. 18 Results: 7 different contrast medias caused negative interference in troponin levels between 57.43% 19 and 62.87%. It was found that different contrast medias produced false negativity in the pro-BNP 20 test ranging from 6.11% to 96.01%. Enzymes and coagulation tests have been less affected. 21 Conclusions: Different contrast medias may cause false negative cTnI and pro-BNP. Therefore, the 22 contrast medias which causes the least interference should be preferred. The results of samples 23 taken in the first hour of contrast imaging should be interpreted with care. 24


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Contrast media are intravenous diagnostic medias used in radiological imaging techniques.

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While contrast media are known to cause clinical side effects after intravenous injection, there has 30 been less interest on the extent of their interference with laboratory results [1]. Timing of this 31 interference appears to be unpredictable, leading to test results that are inconsistent with the clinical 32 presentation. Such inconsistency may cause overlooking cardiac emergencies or delayed diagnosis, 33 thereby affecting morbidity and mortality risks. Severity of interference with contrast media 34 (iohexol, gadobutrol, gadopentetic acid, gadodiamide, ioversol) used during imaging techniques for 35 diagnosis and follow-up purposes may differ depending on the duration of excretion from the body.

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In addition to several interference factors, false low cardiac marker measurements associated with 37 biotin interference have led certain commercial companies to re-assess their measurement

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Subsequently, 20 uL contrast medium was added and mixed on a vortex plate for 5 seconds. A 60 different control solution for each test was read on analyzers. Each measurement was performed in 61 triplicate and mean value of the 3 measurements was calculated. This measurement was performed 62 separately for 7 different contrast media. In order to rule out the interference likely to occur due to the 63 volume expansion with the control material, 20 uL distilled water was added, followed by a triplicate 64 measurement and mean value of the 3 measurements was accepted as the target. Owing to the 65 copyright of commercial companies, commercial names of the contrast media were coded from RS1 to 66 RS7. Ethics committee approval was not deemed necessary since the study did not require any blood 67 or tissue samples of animal or human origin.

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Negative interference was noted for mass CK-MB at a rate of 11.37% with RS5 and 39.02% with RS7.

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All of the contrast medias had negative interference with troponin-I ranging from 57.43% to 62.87%.

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The negative interference with NT-proBNP test was found to be in the range of 6.11% to 96.01%.

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CK, AST and LDH are the biochemistry tests with limited specificity for the evaluation of 117 cardiac functions. Enzymes were the tests exposed to least interference in the present study.

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Negative interference was noted for CK and AST, ranging at 0.93% to 5.12% and up to 4.81%,

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The fact that the performance of these tests depends on antibody affinity facilitates interference [6].