Patient Age Adds Key Context to D-Dimer in DVT Diagnosis: ADJUST-DVT

Age-adjusted D-dimer cutoffs can safely rule out deep vein thrombosis (DVT) in many suspected cases, according to the ADJUST-DVT trial.

For patients ages 50 and older with a nonhigh or unlikely clinical probability of DVT, using the D-dimer threshold of age x 10 μg/L—rather than the one-size-fits-all cutoff of 500 μg/L—increased the diagnostic yield in the study without producing any false negatives.

Led by Grégoire Le Gal, MD, PhD (Ottawa Health Research Institute, Canada), ADJUST-DVT was published earlier this week in JAMA.

Senior author Marc Righini, MD (Geneva University Hospital, Switzerland), said the results expand upon those of the 2014 ADJUST-PE trial, which backed the use of age-adjusted D-dimer cutoffs in pulmonary embolism (PE). “In Europe at least, the age-adjusted cutoff is quite used for pulmonary embolism,” with some centers using it for suspected DVT as well thanks to several retrospective reports, Righini specified.

However, “a prospective outcome study, in which treatment of patients with suspected DVT would be managed without anticoagulants on the basis of a negative age-adjusted D-dimer test result has been lacking,” the paper notes.

“What we really wanted was to have the same cutoff for PE and DVT—to have the same strategy for both,” said Righini. To this end, the data from two large trials are sufficient, he added, noting that no further studies are planned on the topic.

Age-adjusted cutoffs are “very safe,” he commented. “The failure rate is very low.”

Francisco Ujueta, MD (Vanderbilt University Medical Center, Nashville, TN), and Gregory Piazza, MD (Brigham and Women’s Hospital, Boston, MA), in an accompanying editorial, say that D-dimer testing is an “indispensable tool” with high sensitivity and negative predictive value in outpatients who present with suspected venous thromboembolism (VTE).

“However, the lack of specificity of D-dimer testing for VTE, because levels generally increase with advancing age, has long limited its utility in the growing elderly population,” who may face unnecessary ultrasound exams and anticoagulation while awaiting imaging results, they observe.

Ujueta and Piazza note that ADJUST-DVT, despite some caveats related to generalizability, points to “a paradigm shift in the diagnostic strategy for lower extremity DVT: rather than adhere to a rigid universal cutoff, D-dimer interpretation can and should be tailored, at least by age, to allow for more precision.” This shift would be both clinically and economically advantageous, they add.

Age-Based Cutoff Works

ADJUST-DVT enrolled 3,205 outpatients (median age 59 years; 54% female) who presented to the emergency department with suspected DVT at 27 centers in Belgium, Canada, France, and Switzerland. Investigators applied a sequential diagnostic strategy informed by the Wells score, a highly sensitive D-dimer test, and leg compression ultrasonography.

This strategy identified a proximal DVT prevalence of 13.5%.

Among the 2,169 patients deemed to have a nonhigh or unlikely clinical probability based on the Wells test, 24.5% had a D-dimer level less than 500 μg/L and 7.4% had a D-dimer level between 500 μg/L and their age-adjusted cutoff—which translates into a 23.3% relative increase in diagnostic yield by considering age. Within that latter group whose D-dimer level fell between the standard and age-adjusted thresholds, no patients experienced adjudicated symptomatic VTE (leg DVT and/or pulmonary embolism) over 3-month follow-up. In the group with D-dimer levels below 500 μg/L, the rate of symptomatic VTE was 0.2%.

Additionally, among patients ages 75 and older, using the age-adjusted cutoff rather than 500 μg/L increased the proportion of negative D-dimer results from 8.7% to 26.1% without producing any false negatives.

“In clinical practice, this has meaningful implications: enabling more patients to be discharged without imaging, reducing emergency department length of stay, and avoiding unnecessary empiric anticoagulation,” the researchers conclude. “Importantly, these advantages were not offset by any compromise in diagnostic safety.”

The editorialists, while praising the trial for its inclusion of patients with prior VTE, active malignancy, oral contraceptive use, and prolonged immobility, say the findings may not apply to key demographic groups.

In particular, Black individuals tend to have higher D-dimer levels even in the absence of thrombosis, they note. “Accordingly, the clinician is left with a potential concern: could applying the same threshold across racial and ethnic groups not represented in the ADJUST-DVT study inadvertently increase diagnostic error, either by overdiagnosis or missed diagnosis?”

The strategy employed in the trial might also not apply for other common real-world presentations such as “patients with upper extremity symptoms, pregnancy, obesity, and active inflammatory or infectious illness,” Ujueta and Piazza caution.

Even so, they agree, “the implications of ADJUST-DVT have the potential to align the principles of precision medicine with efficiency, patient safety, and value-based care.”