Validation of STA-Liatest D-Di assay for exclusion of pulmonary embolism according to the latest Clinical and Laboratory Standard Institute/Food and Drug Administration guideline. Results of a multicenter management study

Abstract

Combined clinical pretest probability (PTP) and D-dimer testing have great diagnostic value for pulmonary embolism exclusion. To harmonize performance levels of D-dimer assays available on the market, the Clinical and Laboratory Standard Institute (CLSI) has published a guideline, endorsed by the US Food and Drug Administration (FDA). Such guideline specifies the ideal D-dimer assay characteristic and target population. This study was conducted following the CLSI guideline to upgrade the assay-intended use and obtain FDA clearance of STA-Liatest D-Di assay for pulmonary embolism exclusion in patient with low/moderate PTP. This was an international, multicenter, prospective nonrandomized, noninterventional clinical outcome management study conducted in a standard of care setting. D-dimer assay was performed in consecutive, ambulatory outpatients suspected of pulmonary embolism, with low/moderate PTP, and without medical conditions or in clinical settings known to alter default D-dimer values regardless of the presence of thrombosis using a threshold of 0.5 μg/ml (fibrinogen equivalent units) for venous thromboembolism exclusion. Results were used to determine test performance. Of 1141 patients who underwent D-dimer testing, 1060 had valid results and completed study as planned. STA-Liatest D-Di assay performance has exceeded the CLSI/FDA guidance requirements, with a sensitivity of 97.6% (95% confidence interval: 91.7–99.7%) and a negative predictive value of 99.7% (95% confidence interval: 99.0–100%). STA-Liatest D-Di assay has an excellent performance when used in combination with a PTP score in relevant patients and has the potential to minimize the economic healthcare burden avoiding unnecessary and expensive imaging tests.

Age‐adjusted D‐dimer cut‐off leads to more efficient diagnosis of venous thromboembolism in the emergency department: a comparison of four assays

“…Age‐adjusted cut‐offs have been previously validated and recommended in DVT and PE to increase specificity in older patients while preserving sensitivity. However, this has been questioned , and a recent Cochrane review of D‐dimer to rule out pulmonary embolism did not find enough evidence to recommend age‐adjusted cut‐offs .…”

D-Dimer Use and Pulmonary Embolism Diagnosis in Emergency Units: Why Is There Such a Difference in Pulmonary Embolism Prevalence between the United States of America and Countries Outside USA?

“…According to the latest requirements of the Food and Drug Administration (FDA) in the USA, and to be compliant with the new Clinical and Laboratory Standards Institute guideline regarding “Quantitative D-dimer for the Exclusion of Venous Thromboembolic Disease » [17], we conducted the DIET study, an international multicenter (Europe, Canada and USA) prospective study to validate the clinical performance of the STA ® —Liatest ® D-Dimer assay when used in combination with PTP for PE exclusion [18]. In the present manuscript we report and analyze the differences in clinical care leading to the huge difference in observed PE prevalence between the different countries.…”

Age-Adjusted D-Dimer to Rule out Deep Vein Thrombosis: Findings From the PALLADIO Algorithm

“…Pernod et al evaluated 1196 patients < 80 years old with suspected PE and found a similar performance of the conventional and age-adjusted D-dimer thresholds, the latter providing only a 2% increase of patients reclassified as PE ruled out without imaging [14,22]. However, patients with high clinical probability of PTP were excluded in the first study [13] and constituted less than 2% of the second study [14,22], probably because of the limited value of D-dimer in this subgroup of patients who are supposed to undergo imaging tests regardless of D-dimer value. The PALLADIO study, instead, included also patients with likely PTP of DVT, because the aim was not only to reduce the need for CUS but also to identify which patients should be examined for distal DVTs.…”

“…They found that the negative predictive value of Ddimer was above 99% with all three strategies, thus concluding that the classical age-adjusted threshold did not provide a better diagnostic strategy as compared with the mean Ddimer strategy [13]. Pernod et al evaluated 1196 patients < 80 years old with suspected PE and found a similar performance of the conventional and age-adjusted D-dimer thresholds, the latter providing only a 2% increase of patients reclassified as PE ruled out without imaging [14,22]. However, patients with high clinical probability of PTP were excluded in the first study [13] and constituted less than 2% of the second study [14,22], probably because of the limited value of D-dimer in this subgroup of patients who are supposed to undergo imaging tests regardless of D-dimer value.…”