D-dimer diagnostics: can I use any D-dimer assay? Bridging the knowledge-to-action gap

Abstract

A State of the Art lecture titled "D-dimer Diagnostics: Can I use any D-dimer assay? Bridging the Knowledge-to-Action gap" was presented at the International Society on Thrombosis and Haemostasis Congress in 2023, included in the session on the clinical impact of variability in commonly used coagulation assays. Here, we review the role of D-dimer, primarily in the outpatient diagnosis of patients with venous thromboembolism (VTE) when combined with clinical decision rules. We focus on the recent large management trials that have studied adjustments of VTE exclusion thresholds for D-dimer based on either prior clinical probability of VTE or patient age, and the resultant benefit of reduced imaging for VTE and improved diagnostic efficiency. In this context, we report on the significant variability between D-dimer results and the multiple D-dimer assays in use worldwide using data from international external quality assurance programs. This variability is particularly high at typical VTE exclusion thresholds. We discuss the potential clinical impact of D-dimer assay substitution on accuracy of diagnosis and risk stratification of patients with VTE. Finally, we summarize relevant new data on this topic presented during the 2023 International Society on Thrombosis and Haemostasis Congress and outline future priorities urgently needed to harmonize D-dimer results and reporting that will require international collaboration among multiple stakeholders with an overall goal to close this knowledge-to-action gap.

Keywords: D-dimer; diagnosis; external proficiency; quality assurance; venous thromboembolism.

Graphical abstract

Figure 1

D-dimer assay variation in the Royal College of Pathologists of Australasia Quality Assurance Program. Data are shown as the coefficient of variation (CV) of participant-reported D-dimer values, expressed as a percentage and plotted against the averaged D-dimer value for each sample assessed in this program for the years 2018 to 2022 (adjusted to mg/L FEU). Data are shown separately for individual assays.

Figure 2

D-dimer assay variation in the External Quality Control for Assays and Tests Foundation Quality Assurance Program. Data are shown as the coefficient of variation (CV) of participant-reported D-dimer values, expressed as a percentage and plotted against the averaged D-dimer value for each sample assessed in this program for the years 2017 to 2022. Only assays reporting results in mg/L FEU are shown. Data are shown separately for individual assays.

Figure 3

CI around a hypothetical true D-dimer value of 0.55 mg/L fibrinogen equivalent units (FEU) by the method. CI is calculated using method-specific coefficients of variation for a D-dimer value of approximately 0.55 mg/L FEU for assays shown in Figure 2. The proportion of values below 0.50 mg/L FEU is represented by the percentage between brackets.