Age-Adjusted D-Dimer Cutoff Levels to Rule Out Deep Vein Thrombosis
Grégoire Le Gal, Helia Robert-Ebadi, Venkatesh Thiruganasambandamoorthy, Farès Moustafa, Andréa Penaloza, Judith Catella, Marie Chevallier Grenot, Shaun Visser, Lucia Mazzolai, Alain Plumacker, Stefano Barco, Eddy Lang, Vicky Tagalakis, Claire Déroche, Meghan Garnett, Jennifer Hulme, Pierre-Marie Roy, Alexandre Ghuysen, F. Couturaud, Rolf P. Engelberger, D. El Kouri, D. Aujesky, Marc Righini, ADJUST-DVT Investigators, Anne Le COAT, Marion Douplat, Motte Serge, Christina JEANNERET, Marc Blondon, Fréderic Glauser, Pierre Youatou Towo, Andrea PASCU CIOBANU, Raphaëlle Lopez, Florence Dupriez, Maximilien Thoma, Lara Absil, Marc CARRIER, Lana CASTELLUCCI, Aurélien DELLUC, Cathy Code, Melissa FORGIE, Alan Karovitch, Miriam Kimpton, Lisa Duffett, Leon Rivlin, Phil DAVIS, Dimitri Scarvelis, Joseph R. Shaw, Deborah Siegal, Tzu-Fei WANG, Philip WELLS, Gina MANCA, Mary Naciuk, Riccardo M. Fumagalli, Jean-Baptiste Dexpert
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.