Investigation of age-adjusted D-dimer using an uncommon assay.

Background: Use of an age-adjusted D-dimer for the evaluation of acute pulmonary embolus (PE) has been prospectively validated in the literature and has become a practice recommendation from major medical societies. Most research on this subject involves the most common D-dimer assays reporting in Fibrinogen Equivalent Units (FEU) with a non-age-adjusted manufacturer-recommended cutoff of 500 ng/ml FEU. Limited research to date has evaluated age-adjustment in assays that report in D-Dimer Units (D-DU), which use a manufacturer-recommended cutoff of 230 ng/ml D-DU. Despite scant evidence, an age-adjusted formula using D-DU has been recently endorsed by the American College of Emergency Physicians (ACEP). This formula seems arbitrary in its derivation and unnecessarily deviates from existing thresholds, thus prompting the creation of our novel-age adjustment formula. The goal of this study was to retrospectively evaluate the test characteristics of our novel age-adjusted D-dimer formula using the D-DU assay in comparison to existing traditional and age-adjusted D-dimer thresholds for the evaluation of acute PE in the ED.

Methods: This was a retrospective chart review at an academic quaternary health system with three EDs and 195,000 combined annual ED visits. Only patients with D-dimer testing and CT PE protocol (CTPE) imaging were included. Admission and discharge diagnosis codes were used to identify acute PE. Outcome measures were sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of an unadjusted traditional threshold (230) compared with both novel and ACEP-endorsed age adjusted thresholds, (Age × 5) - 20 and Age × 5 if >50, respectively. Estimates with their exact 95% threshold were performed.

Results: 4846 adult patients were evaluated from January 2012 to July 2017. Group characteristics include a mean age of 52 and a frequency of acute PE diagnosis by CTPE of 8.25%. Traditional D-dimer cutoff demonstrated a sensitivity of 99.8% (95% CI 98.6-100), specificity of 16.7% (95% CI 15.6-17.8) and NPV of 99.9% (95% CI 99.3-100). Our novel age-adjusted D-dimer thresholds had a sensitivity of 97.0% (95% CI 94.8-98.4), specificity of 27.9% (95% CI 26.6-29.2) and NPV of 99.0% (95% CI 98.3-99.5) with the ACEP-endorsed formula demonstrating similar test characteristics.

Conclusion: Use of an age-adjusted D-dimer on appropriately selected patients being evaluated for acute PE in the ED with a D-DU assay increases specificity while maintaining a high sensitivity and NPV. Both our novel formula and the ACEP-endorsed age-adjusted formula performed well, with our novel formula showing a trend towards improved testing characteristics.