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. 2026 Jan 5:e2521561.
doi: 10.1001/jama.2025.21561. Online ahead of print.

Age-Adjusted D-Dimer Cutoff Levels to Rule Out Deep Vein Thrombosis

Grégoire Le Gal  1   2 , Helia Robert-Ebadi  3 , Venkatesh Thiruganasambandamoorthy  1   4 , Fares Moustafa  5 , Andrea Penaloza  6 , Judith Catella  7 , Marie Chevallier Grenot  8 , Shaun Visser  9 , Lucia Mazzolai  10 , Alain Plumacker  11 , Stefano Barco  12 , Eddy Lang  13 , Vicky Tagalakis  14 , Claire Deroche  15 , Meghan Garnett  16 , Jennifer Hulme  17 , Pierre-Marie Roy  18 , Alexandre Ghuysen  19 , Francis Couturaud  20   21 , Rolf Engelberger  22 , Dominique El Kouri  23 , Drahomir Aujesky  24 , Marc Righini  3 ; ADJUST-DVT Investigators
Collaborators, Affiliations

Age-Adjusted D-Dimer Cutoff Levels to Rule Out Deep Vein Thrombosis

Grégoire Le Gal et al. JAMA. .

Abstract

Importance: The age-adjusted D-dimer cutoff (age × 10 µg/L in patients 50 years or older), safely increases the diagnostic yield of D-dimer in patients with suspected pulmonary embolism but has not been validated in patients with suspected leg deep vein thrombosis (DVT).

Objective: To prospectively validate whether using an age-adjusted D-dimer cutoff allows clinicians to safely rule out DVT.

Design, setting, and patients: Multicenter, multinational prospective management outcome study conducted in 27 centers in Belgium, Canada, France, and Switzerland between January 2015 and October 2022 (last follow-up visit, January 30, 2023) and including outpatients presenting to the emergency department with suspected DVT.

Interventions: Patients were assessed by a sequential diagnostic strategy based on the assessment of clinical pretest probability by the Wells score, a highly sensitive D-dimer test, and leg compression ultrasonography. Patients in whom DVT was ruled out were followed up for a 3-month period.

Main outcome and measure: The primary outcome was the rate of adjudicated symptomatic venous thromboembolic events during follow-up in patients in whom DVT was ruled out based on a D-dimer value between the conventional cutoff of 500 µg/L and their age-adjusted cutoff.

Results: A total of 3205 patients were included. Median age was 59 years, and 1737 (54%) were female. DVT prevalence was 14%. Among the 2169 patients with a non-high or unlikely clinical probability, 531 (24.5% [95% CI, 22.7%-26.4%]) had a D-dimer level less than 500 µg/L, and 161 additional patients (7.4% [95% CI, 6.4%-8.6%]) had a D-dimer level between 500 µg/L and their age-adjusted cutoff. No failures were identified in patients with a D-dimer level 500 µg/L or greater but below the age-adjusted cutoff (0% [95% CI, 0%-2.3%]). Among patients 75 years or older, using the age-adjusted cutoff instead of the 500-µg/L cutoff increased the proportion of negative D-dimer from 33 of 379 (8.7% [95% CI, 6.3%-12.0%]) to 99 of 379 (26.1% [95% CI, 22.0%-30.8%]), without any false-negative test results.

Conclusions and relevance: The age-adjusted D-dimer cutoff may safely rule out DVT and was associated with a larger number of patients in whom DVT could be effectively ruled out.

Trial registration: ClinicalTrials.gov Identifier: NCT02384135.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Le Gal reported receiving lecture honoraria not taken as income from Emcure and Takeda outside the submitted work. Dr Thiruganasambandamoorthy reported receiving support through a Physicians’ Services Incorporated Foundation Mid-Career KT fellowship award and University of Ottawa Tier-1 Clinical Research Chair in Cardiovascular Emergencies award; receiving grant funding from Physicians’ Services Incorporated Foundation, Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Networks of Centres of Excellence through the Cardiac Arrhythmia Network of Canada (CANet), Ontario Centres of Innovation, and The Ottawa Hospital Academic Medical Organization; and serving as a consultant for the National Institutes of Health–funded project Practical Approaches to Care in Emergency Syncope (PACES). Dr Penaloza reported receiving support for symposia and research from Bayer, Daiichi, LEO Pharma, Viatris, BMS/Pfizer, Sanofi, Becton Dickinson, and Charities Aid Foundation and receiving support for a study sponsored by Stago outside the submitted work. Dr Garnett reported receiving grants from the Heart and Stroke Foundation of Canada during the conduct of the study and that she is an associate professor at NOSM University. Dr Roy reported receiving personal fees from Viatris Sante, Sanofi Winthrop Industry, Pfizer SAS, and Bristol Myers Squibb and receiving grants from the French Ministry of Health outside the submitted work. Dr Couturaud reported receiving research grants from BMS/Pfizer and Merck Sharp and Dohme, travel support from Sanofi, and personal fees from LEO Pharma and GlaxoSmithKline outside the submitted work. No other disclosures were reported.

Comment in

References

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