Raising the D-dimer threshold: Fewer CTs and no missed PEs?

EBM Focus - Volume 15, Issue 2

Reference: N Engl J Med. 2019 Nov 28;381(22):2125-2134

Chest imaging for diagnosis of pulmonary embolism has dramatically risen over the past two decades (Feng et al 2013). Several clinical prediction tools intended to reduce unnecessary imaging and exposure to radiation and contrast have been developed. Among patients with a low clinical probability of pulmonary embolism, an age-adjusted D-dimer cut-off for patients age ≥ 50 years has been found to safely rule out pulmonary embolism. Alternatively, the YEARS algorithm, which uses three clinical criteria plus the D-dimer, has also been found to reduce the need for imaging and has a false negative rate of < 1%.

The PEGeD study was a trial of over 2,000 non-pregnant adults presenting to emergency departments throughout Canada with signs or symptoms suggestive of pulmonary embolism. Clinicians used the Wells score to assign low (0-4), moderate (4.5-6), or high (≥ 6.5) pretest probability of pulmonary embolism. Those with a D-dimer value < 1,000 ng/mL in the low pretest probability group or < 500 ng/mL in the moderate group had only clinical follow-up. All others had immediate imaging with CT pulmonary angiography or ventilation-perfusion scanning.

In initial testing, pulmonary embolism was diagnosed in 5% of the low-risk group with a D-dimer ≥ 1,000 ng/mL, 20% of the moderate-risk group with a D-dimer ≥ 500 ng/mL, and 40% of the high-risk group. None of the 1,325 patients with a D-dimer below the cut-off (< 500 ng/mL in moderate clinical probability and < 1,000 ng/mL in low probability) who participated in follow-up had a pulmonary embolism when assessed at 3 months via telephone or in clinic. However, there was a differential loss to follow-up: 13 patients in the low pretest probability group were lost to follow-up and not accounted for either qualitatively or statistically. All patients in the intermediate- or high-risk groups were followed up.

The biggest change in evaluating patients with suspected PE based on this protocol is using 1,000 ng/dL as a cutoff for patients with low clinical pretest probability rather than 500 ng/dL or an age adjusted threshold. The net effect was a reduction in the percentage of low risk patients who needed imaging studies from 45% to 27%. However, the largest concern with this study is that we don’t know what happened to the 13 patients lost to follow-up in the low-risk group; how are we to know these patients didn’t have fatal pulmonary embolisms? While this study is interesting, changing practice based on these data alone makes us nervous and we’d like to see additional studies first.

For more information, see the topics Clinical Prediction of Pulmonary Embolism and D-dimer Testing for Pulmonary Embolism in DynaMed.

DynaMed EBM Focus Editorial Team

This EBM Focus was written by Carina Brown, MD, Assistant Professor at Cone Health Family Medicine Residency. Edited by Alan Ehrlich, MD, Executive Editor at DynaMed and Associate Professor in Family Medicine at the University of Massachusetts Medical School, Dan Randall, MD, Deputy Editor for Internal Medicine at DynaMed, and Katharine DeGeorge, MD, MS, Associate Professor of Family Medicine at the University of Virginia and Clinical Editor at DynaMed.