A prospective validation study showed that using a newer, higher D-dimer cutoff can safely rule out leg deep vein thrombosis (DVT) in a larger proportion of patients. This approach reduced the need for additional imaging tests (such as venous ultrasound) and avoided unnecessary anticoagulation, without compromising patient safety. The findings support more efficient and patient-friendly DVT diagnostic pathways. The study was published in JAMA by Gregoire L. and colleagues.
The aim of this study is to prospectively validate that by using an age-adjusted D-dimer cutoff of age multiplied by 10 µg/L for patients aged 50 years and older, it would be safe to rule out deep vein thrombosis in outpatients who present to emergency departments for lower extremity DVT. This is an international multicenter management outcome study that took place in 27 centers in Belgium, Canada, France, and Switzerland. The recruitment of patients took place from January 2015 to October 2022; also, the final follow-up assessment was done on January 30th, 2023. This study recruited outpatients that went to emergency departments for lower extremity DVT.
All patients underwent a sequential diagnostic strategy that included assessment of clinical pretest probability with the Wells score, a highly sensitive D-dimer assay if indicated, and leg compression ultrasonography. Patients with a DVT ruled out by this approach did not receive anticoagulation and were followed for a period of 3 months for symptomatic venous thromboembolic events.
Key findings:
There were 3205 patients in this analysis; the median age was 59 years and 1737 patients were female (54%).
The overall prevalence of confirmed DVT in the study population was 14%, which is representative of a real-world emergency department cohort with suspected disease.
In the 2169 patients with a low clinical probability of DVT, 531 (24.5% [95% CI, 22.7%-26.4%]) had D-dimer concentrations below the fixed threshold of 500 µg/L, and 161 (7.4% [95% CI, 6.4%-8.6%]) had D-dimer concentrations of 500 µg/L or higher but below the age-adjusted threshold.
Notably, no diagnostic failures occurred in the latter group, and the VTE event rate was 0% (95% CI, 0%-2.3%).
The age-adjusted D-dimer strategy was highly beneficial in the older patients. In patients aged 75 years and older, the 500 µg/L threshold sensitive strategy identified 33 of 379 patients (8.7% [95% CI, 6.3%-12.0%]) as having D-dimer-negative results.
The age-adjusted D-dimer threshold strategy identified 99 of 379 patients (26.1% [95% CI, 22.0%-30.8%]) as D-dimer negative and did not have any false negatives in the older age group.
An age-adjusted D-dimer threshold safely cleared the diagnosis of deep vein thrombosis and significantly improved the posttest probability of patients from whom DVT could be ruled out without imaging. This prospective international study confirms the use of age-adjusted D-dimer thresholds as useful components of diagnostic strategies for the evaluation of suspected DVT, particularly in older patients.
Reference:
Le Gal G, Robert-Ebadi H, Thiruganasambandamoorthy V, et al. Age-Adjusted D-Dimer Cutoff Levels to Rule Out Deep Vein Thrombosis. JAMA. Published online January 05, 2026. doi:10.1001/jama.2025.21561
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