Analytical performance of the Albumin Cobalt Binding (ACB®) test on the Cobas MIRA® Plus analyzer

Abstract

Recently a new biological marker, Ischemia Modified Albumin (IMA), measured by the Albumin Cobalt Binding (ACB) test, was introduced for detection of myocardial ischemia. During ischemia, the metal binding capacity of albumin for certain transition metals like cobalt is reduced. The precise mechanism of action for producing IMA is not known but appears to be related to the production of reactive oxygen species that modify the metal binding sites. The ACB test is a quantitative assay that detects IMA by measuring the cobalt binding capacity of albumin in human serum. We evaluated the analytical characteristics of the ACB test, and reagent and specimen stability, using the Cobas MIRA Plus instrument. Coefficients of variation for within-run and between-run assays were <4%. No significant interference was observed for concentrations of triglycerides and hemoglobin up to 7 mmol/l and 3.8 g/l, respectively. No interference was apparent with bilirubin. Measures from paired samples of heparinized plasma and serum were not equivalent. The assay is validated for commercial use with serum, therefore our study reported results for serum specimens only. All assays were completed within 5 hours after blood withdrawal. The one-sided upper 95th percentile, calculated for the ACB test in 150 healthy subjects, was 87.00 U/ml. There was no observed difference between men and women or with age. We conclude that the ACB test adapted on the Cobas MIRA Plus analyzer is satisfactory, but strict attention to sample handling procedures is necessary to maintain stability of the analyte.

Effect of hemodialysis on traditional and innovative cardiac markers

“…The combination of IMA with myoglobin, CK MB, and cardiac troponins increases the diagnostic sensitivity for myocardial infarction in the general population up to 97%, with a negative predictive value of 92% (26). Although the definitive mechanism of action for producing IMA during ischemia is unclear, the metal binding capacity of albumin for transition metals like cobalt is reduced as a consequence of the generation of reactive oxygen species that modify the metal binding capacity of the albumin moiety (31). A variety of heterogeneous ischemic conditions, including endothelial and extracellular hypoxia, acidosis, free radical injury, and sodium and calcium pump disruptions, have been associated with rapid modifications of the cobalt binding properties (47)(48)(49).…”

Evaluation of the albumin cobalt binding (ACB®) assay for measurement of ischaemia-modified albumin (IMA®) on the Beckman Coulter LX-20

“…6,7,19--22 Increases in IMA concentrations have also been reported in conditions not associated with myocardial ischaemia such as skeletal muscle ischaemia, gastrointestinal ischaemia, stroke, end stage renal disease and some neoplasms. 9,23--27 The ACB test is currently available only on Roche instrumentation 28 (Roche Modular P and 911 and Cobas Mira Plus) and the Beckman Coulter LX-20. As far as we are aware, this is the ¢rst published independent evaluation of the ACB assay on the Beckman Coulter LX-20.…”

Estimation of Ischemia Modified Albumin (IMA) Levels in Patients with Acute Coronary Syndrome

“…In this connection, ischemia modified albumin (IMA) is among the several biomarkers under investigation [7]. The precise mechanism for IMA generation is not yet known, though it appears that reactive oxygen species (ROS), produced during ischemia and ischemia-reperfusion, generate highly reactive hydroxyl free radicals resulting in site-specific modification of the N-terminus of the albumin moiety, especially of the N Asp-Ala-His-Lys sequence [8,9], which result in a significant change in the ability of albumin to bind transition metals, notably, cobalt [10]. It has been shown that the concentration of IMA increases within a couple of minutes from the onset of ischemia and remains elevated until 6-12 h and returns to its normal range after 24 h [11].…”