A-227 Comprehensive overview of preliminary interference data for a new D-dimer assay

Abstract

D-dimer is a soluble fibrin degradation product generated during the regulated breakdown of thrombin by the fibrinolytic system and represents a key biomarker in hemostasis. Measurement of D-dimer is of major importance in clinical diagnostics, particularly for the assessment of thrombotic events, such as deep vein thrombosis (DVT) and pulmonary embolism (PE). Accuracy of D-Dimer assay results, especially at the cutoff level, is crucial for diagnosis. Specimen-specific inaccuracy due to the presence of interfering substances could be interpreted as a change in patient condition. Consequently, understanding the interfering potential of endogenous and exogenous substances is of substantial importance. In this context, the INNOVANCE D-Dimer 2.0 assay designed for the quantitative determination of D-dimer was investigated with respect to the impact of potentially interfering substances on its analytical performance. The INNOVANCE D-Dimer 2.0 assay kit is composed of liquid and ready-to use components as well as a lot-specific calibrator. Three levels of liquid and ready to use quality controls are available and include a negative control, a slightly positive and a higher positive control. Applications are available for the CN-3000/CN-6000, CS-2500/CS-5100 and CA-660 systems. For CN/CS systems, the initial measuring interval is 0.19 to 7.5 mg/L FEU and can be extended to 80 mg/L FEU by automatic redilution. Interference studies were performed in accordance with CLSI EP37 3rd edition for a range of endogenous and exogenous substances. The substances tested included hemoglobin, bilirubin, lipids, albumin, creatinine, immunoglobulin G (IgG), urea, uric acid, as well as more than 35 prescription and over the counter (OTC) drugs at concentrations above their therapeutic ranges or other and representative of the intended use population. The assessment was conducted using either the paired difference approach or the dose response approach. In addition, interference from human anti-mouse antibodies (HAMA) and rheumatoid factors (RF) was evaluated by patient coagulations. No interference was observed for hemoglobin up to 1000 mg/dL, for unconjugated bilirubin up to 60 mg/dL, for conjugated bilirubin up to 40 mg/dL, and for lipids up to 300 mg/dL, when using the CS-5100 system, and compared well across the other analyzers. No interference was observed for the remaining endogenous substances up to the following concentrations: 5.8 g/dL albumin; 75 mg/dL creatinine; 3.3 g/dL IgG; 500 mg/dL urea; 31 mg/dL uric acid. The exogenous substances dextrane 40 and valproic acid demonstrated no interference up to 1200 mg/dL and 19 mg/dL, respectively. All other exogenous substances showed no interference up to the test concentrations. Overall, the INNOVANCE D-Dimer 2.0 assay demonstrated robust performance across a wide range of potentially interfering substances. The assay provides reliable results for the quantitative determination of D-dimer. The INNOVANCE D-Dimer 2.0 assay mentioned herein is not commercially available in all countries. Its future availability cannot be guaranteed.