February 2025 Pick of the Month

It Is About the Math

This month’s Pick of the Month presents the “flat-Earth” work by Bannelier et al, Failure rate of D-dimer testing in patients with high clinical probability of pulmonary embolism: Ancillary analysis of three European studies. Multiple systematic reviews with meta-analyses have demonstrated that in pooled data, the likelihood ratio (LR) of a negative D-dimer is lower than a negative computerized tomographic pulmonary angiography (CTPA).  Thus, at all strata of pretest probability, the negative D-dimer produces a lower posterior probability for PE (false negative rate) than does the negative CTPA. 

The present work brings this little recognized fact to the forefront, even if the threshold for abnormal is age-adjusted (typically age*10 as the threshold in ng/mL, but this depends on the D-dimer machine). It challenges the currently accepted dogma of all published “rule out” protocols for PE which mandate that patients with high pretest probability proceed directly to CTPA. While this is not logical from the LR(-) math, from a throughput standpoint, this is reasonable, inasmuch as the D-dimer is more likely than not to be positive in the approximately 10% of patients tested for PE and who have a high pretest probability.

In real practice, the importance of the work by Bannelier et al, is that it provides an alternative if the CTPA cannot be performed, or if the CTPA has low opacification or other artifact rendering it indeterminant—a problem in about 5% of CTPAs done for patients with high pretest probability. In these scenarios, the negative D-dimer is a reasonable and prudent method to exclude PE, and withhold anticoagulation, at least for today. 

Jeffrey A. Kline, MD
Wayne State University School of Medicine
Editor-in-Chief

Source: Kirsty Challen, BSc, MBChB, MRes, PhD, Lancashire Teaching Hospitals | AEM Editor of Infographics