Age-adjusted D-dimer cutoff appears better at ruling out PE

D-dimer cutoffs adjusted for age performed better than a fixed D-dimer cutoff for safely ruling out pulmonary embolism (PE), especially in elderly patients, according to a new study.

Researchers performed a multicenter prospective management outcome study in 19 centers in Europe from Jan. 1, 2010, to Feb. 28, 2010. The study's objective was to prospectively validate whether an age-adjusted D-dimer cutoff (age × 10 in patients ≥50 years of age) had better diagnostic yield than the conventional D-dimer cutoff in patients in whom PE was suspected. The study involved consecutive outpatients who presented to EDs with clinically suspected PE, defined as acute-onset or worsening shortness of breath or chest pain without another obvious cause.

Patients were evaluated by a sequential diagnostic strategy that was based on clinical probability according to the simplified revised Geneva score or the 2-level Wells score; highly sensitive D-dimer measurement; and CT pulmonary angiography (CTPA). Patients whose D-dimer value fell between the usual cutoff (500 μg/L) and their age-adjusted cutoff didn't receive CPTA or treatment but were formally followed for 3 months. The study's primary outcome was the diagnostic strategy's failure rate, as defined by thromboembolic events during the 3 months of follow-up in patients who didn't receive anticoagulants because of a negative age-adjusted D-dimer result. Three independent experts who were blinded to the criteria for ruling out PE at study inclusion adjudicated all suspected venous thromboembolic events and deaths. The study results appeared in the March 19 Journal of the American Medical Association.

Overall, 3,346 patients with suspected PE were initially included in the study. Of these, 22 did not have a D-dimer test performed and 1 withdrew consent. The prevalence of PE was 19%. A total of 2,898 patients had a nonhigh or unlikely clinical probability of PE, and of these, 817 (28.2%) had a D-dimer level below 500 μg/L and 337 had a D-dimer level that fell between the conventional cutoff and their age-adjusted cutoff. Patients with a D-dimer level higher than 500 μg/dL but lower than their age-adjusted cutoff had a 3-month diagnostic failure rate of 0.3% (95% CI, 0.1% to 1.7%).

Seven hundred seventy-six patients were at least 75 years old, and of these, 673 had a nonhigh clinical probability of PE. In this group of older patients, the age-adjusted cutoff versus the 500 μg/L cutoff allowed more patients to have PE excluded based on D-dimer testing (200 of 673 vs. 43 of 673, or 29.7% vs. 6.4%). No additional false-negative findings were noted with use of the age-adjusted cutoff in this group.

The authors noted that their study was not randomized and that the different institutions involved used different tools to assess pretest probability, as well as different commercial D-dimer assays, among other limitations. However, they concluded that age-adjusted D-dimer cutoffs, when combined with probability assessment, ruled out PE in more ED patients than the conventional cutoff and were associated with a low risk for subsequent symptomatic venous thromboembolism, especially in patients at least 75 years of age.

“Future studies should assess the clinical usefulness of the age-adjusted D-dimer cutoff in clinical practice,” the authors wrote. “Whether the age-adjusted cutoff can result in improved cost-effectiveness or quality of care remains to be demonstrated.”