Using an age-adjusted D-dimer cutoff safely increased the proportion of patients in whom deep vein thrombosis could be ruled out without additional imaging, according to a large multinational prospective study published in JAMA.
The study evaluated whether applying an age-adjusted D-dimer threshold, defined as age × 10 µg/L in patients aged 50 years or older, could safely exclude deep vein thrombosis (DVT) while improving diagnostic efficiency. Although age-adjusted D-dimer thresholds have been validated for suspected pulmonary embolism, evidence supporting their use in suspected lower extremity DVT has been limited.
The multicenter management outcome study included 3,205 outpatients treated at 27 centers in Belgium, Canada, France, and Switzerland between January 2015 and October 2022, with follow-up completed in January 2023. Researchers assessed patients using a sequential diagnostic strategy incorporating clinical pretest probability via the Wells score, a highly sensitive D-dimer assay, and leg compression ultrasonography when indicated. Patients in whom DVT was ruled out were followed for 3 months for symptomatic venous thromboembolic events.
The median patient age was 59 years, 54% were women, and the overall prevalence of DVT was 14%. Among 2,169 patients with a non-high or unlikely clinical pretest probability, 531 (25%) had D-dimer levels below the conventional cutoff of 500 µg/L. An additional 161 patients (7%) had D-dimer levels between 500 µg/L and their age-adjusted cutoff.
No symptomatic venous thromboembolic events occurred during 3-month follow-up among patients whose D-dimer levels fell between the standard and age-adjusted thresholds. Overall, use of the age-adjusted cutoff resulted in a 7% absolute increase in the proportion of patients in whom DVT could be safely excluded without imaging.
The benefit was most pronounced in older adults. Among patients aged 75 years or older, the proportion of negative D-dimer results increased from 9% using the standard cutoff to 26% with the age-adjusted cutoff, without any false-negative findings.
The researchers concluded that applying an age-adjusted D-dimer cutoff may safely rule out DVT in a larger proportion of patients, reducing the need for compression ultrasonography and improving diagnostic efficiency in the emergency department setting.
In an accompanying editorial, Francisco Ujueta, MD, of Vanderbilt University Medical Center, and Gregory Piazza, MD, of Brigham and Women’s Hospital, noted that D-dimer levels increase with age, limiting test specificity in older patients and often leading to unnecessary imaging and empiric anticoagulation. They emphasized that integrating age-adjusted thresholds with established clinical probability assessments, such as the Wells criteria, represents a refinement of current diagnostic strategies that may improve value-based care without compromising patient safety.
The editorial authors cautioned that the study included limited data on Black patients, a population shown in multiple observational studies to have elevated D-dimer levels even in the absence of thrombosis, raising questions about generalizability.
Disclosures can be found in the published research and editorial.