Adapted D-dimer thresholds safe, efficient to rule out acute pulmonary embolism

For patients with suspected pulmonary embolism, diagnostic strategies to rule out PE that apply adapted D-dimer thresholds were safe and efficient, even in high-risk patients.

Researchers reported results of an international systematic review and individual patient data meta-analysis that included more than 20,000 patients with suspected PE. The data were published in Annals of Internal Medicine.

Milou A.M. Stals, MD, from the department of thrombosis and hemostasis at Leiden University Medical Center, the Netherlands, and colleagues scanned the MEDLINE database for studies that evaluated safety and efficiency of the Wells and revised Geneva scores combined with fixed and adapted D-dimer thresholds as well as the YEARS algorithm to rule out acute PE and were published from 1995 to 2020. The researchers’ search yielded 16 studies that included 20,553 participants.

Efficiency, which the researchers defined as the proportion of participants classified as “PE considered excluding” without an imaging test, was highest across all diagnostic strategies among patients aged younger than 40 years (47% to 68%) and was lowest among patients who aged 80 years and older (6% to 23%) and patients with cancer (9.6% to 26%).

The researchers reported improvement in efficiency among these patient subgroups when pretest probability-dependent D-dimer thresholds of 500 µg were applied.

Predicted failure rates were highest for diagnostic strategies with adapted D-dimer thresholds; rates varied from 2% to 4% in the patient subgroups.

“Overall, the studied strategies might all be considered safe across the predefined patient subgroups, which does not allow for favoring one over the other. Importantly, this conclusion was drawn on the basis of the arguments of the Bayes theorem as well as verification and misclassification bias, which may have led to an overestimation of the failure rate of strategies with adapted D-dimer thresholds. From an efficiency perspective, this IPDMA supports the use of these adapted D-dimer thresholds,” Stals and colleagues wrote. “Pending the results of ongoing diagnostic randomized trials, physicians and guideline committees should balance the interlink between safety and efficiency of available diagnostic strategies.”

In an accompanying editorial, Daniel J. Brotman, MD, professor of medicine at Johns Hopkins University School of Medicine and director of the division of hospital medicine at Johns Hopkins Hospital, noted that “[it] is likely that patients who have marginally elevated D-dimer levels, regardless of the threshold used, have a better prognosis than those with extreme elevations, even when a small PE is missed.

“With these considerations and caveats in mind — all of which favor using higher D-dimer cutoffs in selected patients — the important work by Stals and colleagues offers reassurance that modifying D-dimer thresholds according to age or pretest probability is safe enough for widespread practice, even in high-risk groups,” Brotman wrote.

Reference:

Brotman DJ, et al. Ann Intern Med. 2021;doi:10.7326/M21-4295.