Adapting D-dimer thresholds according to age or pretest probability is safe and efficient for ruling out pulmonary embolism, even in high-risk groups, according to results of a systematic review and individual-patient meta-analysis.

“How diagnostic strategies for suspected pulmonary embolism (PE) perform in relevant patient subgroups defined by sex, age, cancer, and previous venous thromboembolism (VTE) is unknown,” Dr. Frederikus Klok of Leiden University Medical Center, in the Netherlands, and colleagues note in a report in Annals of Internal Medicine.

To investigate, they identified 16 studies that assessed the value of bedside clinical decision rules (the Wells score and the Geneva score) coupled with fixed and adapted D-dimer levels, as well as the YEARS algorithm, for ruling out PE in high-risk groups.

They obtained individual patient data and D-dimer levels for more than 20,000 individuals to evaluate the utility of different D-dimer thresholds.

D-dimer cutoffs were either fixed at 500 mcg/L or modified based on age (with D-dimer threshold set 10 mcg/L higher for each year of age over 50) or pretest probability (with D-dimer threshold set at 1,000 mcg/L for patients with no signs or symptoms of DVT or hemoptysis who have a potential alternate diagnosis that is more likely than PE – the YEARS algorithm).

Across all strategies, the proportion of individuals classified by the strategy as “PE considered excluded” without imaging tests (efficiency) was highest in patients younger than 40 years (47% to 68%) and lowest in patients aged 80+ (6.0% to 23%) or cancer patients (9.6% to 26%).

However, efficiency improved “considerably” in these subgroups when D-dimer levels based on pretest probability were applied.

With adapted D-dimer strategies, the diagnostic failure rate (the predicted incidence of VTE at three months after excluding PE without imaging) ranged from 2% to 4% in these high-risk groups.

The authors caution, however, that due to various factors in these high-risk individuals, it’s likely that their analysis “overestimated” the predicted failure rates of strategies with adapted D-dimer thresholds.

In a linked editorial, Dr. David Brotman of Johns Hopkins University in Baltimore, Maryland, says this “important” work provides “reassurance that modifying D-dimer thresholds according to age or pretest probability is safe enough for widespread practice, even in high-risk groups.”

The results also affirm what is currently known about D-dimer testing for suspected VTE, Dr. Brotman says. Namely, that conditions that predispose to thrombosis through activated hemostasis – such as advanced age, cancer, inflammation, prolonged hospitalization, and trauma – “drive D-dimer levels higher independent of the presence or absence of radiographically apparent thrombosis.”

“Not only are patients with these conditions at high risk for VTE, they are also unlikely to have normal D-dimer levels regardless of the cutoff used. Furthermore, even if they do not have VTE at the time of the initial diagnostic evaluation, they may subsequently develop it during follow-up, particularly if their thrombotic risk factors persist,” Dr. Brotman notes.

“Therefore, high-risk patients should be made aware of the signs and symptoms of potential VTE so that they can seek medical attention promptly in the event of new symptoms, regardless of whether they have VTE at baseline,” he cautions.

Funding for the study was provided by the Dutch Research Council.