It’s the Monday after Thanksgiving, so it’s time to turn the brains back on – and notice an oddly robust cultivation of articles worthy of comment dropped just before the holiday. This is the first, the “Pulmonary Embolism Graduated D-Dimer” (PEGeD) study, a rather obtuse name for what is effectively a pretest likelihood-adjusted implementation of D-dimer. This is also, effectively, what was done with the YEARS protocol – so, what’s new?
In this iteration of the concept, the authors use the Wells score, stratifying patients to either low, moderate, or high probability. A few published work-up algorithms describe pathways of care in which low probability leads to PERC, while the higher-risk cohort undergoes D-dimer testing or directly to CTPA to rule out PE. In this algorithm, those with “low” probability still undergo D-dimer testing – but with a cut-off threshold of 1000 ng/mL warranting advanced imaging. The primary outcome was symptomatic, objectively-verified venous thromboembolism, including PE and deep venous thrombosis, at 90 days.
These authors enrolled a cohort of 2,017 patients between 2015 and 2018, with 1,752 in the “low” probability cohort, 218 “moderate”, and 47 “high”. Overall prevalence of PE on initial testing was 7% and advanced imaging was performed on 34%, for an imaging yield of 24%. The general finding of most importance to the practicing clinician is their observation that 1,285 low-risk patients had D-dimer <1000 ng/mL and 40 moderate-risk patients had D-dimer <500 ng/mL and none had VTE detected at 90 day follow-up. Helpfully, these authors even compare their yield directly to the YEARS protocol – and find about 40 fewer patients would have undergone imaging with PEGeD than YEARS, which makes it basically a wash. They also compare their strategy to an age-adjusted D-dimer, which is a bit odd, considering they are not competing strategies, but synergistic.
The idea of pretest-adjusted D-dimer has been around a very long time, dating back to at least 2012. There’s nothing magical about a cut-off of 1000 ng/mL other than Round Numbers, but it is a serendipitously reasonable starting point for this approach. The real elephant in the room, however, is there were only 87 PEs in their low-risk cohort, for a prevalence of 4.9%. This may yet even over-represent the prevalence of PE in community practice in certain settings (read: the United States). Considering the accepted miss rate for PE is considered to be at least 1%, owing to the likelihood of false-positives and harms from anticoagulation, it is likely an even more aggressive cut-off or imaging-elimination strategy should be pursued.
However, I certainly do not want to minimize this work – adding good, prospective data pushing imaging stewardship is of great importance, whatever minor shortcomings might be observed. At the very least, please considering using PEGeD or YEARS as the basis for your imaging algorithm – and add age-adjusted D-dimer on top for even better reductions in unnecessary imaging.
“Diagnosis of Pulmonary Embolism with d-Dimer Adjusted to Clinical Probability”
https://www.nejm.org/doi/full/10.1056/NEJMoa1909159