D-Dimer for Excluding the Diagnosis of PE

Written by: Alex Chen, MD

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In this systematic review, the D-Dimer was 100% sensitive in low risk Geneva (0-3), intermediate-risk Geneva (4-10), and Wells non-high risk (≤4) for detecting PE. Specificity dropped (more false-positives) as age increased in the Wells non-high risk patients.

Why does this matter?
D-dimer has high sensitivity, making it a good screening test.  But the specificity is low, meaning lots of false positives.  The best practice for D-dimer is to use it in conjunction with a clinical assessment of the pretest probability of disease: Wells, Geneva, or modified dichotomous versions. In this review, up to 25% of patients who presented with symptoms concerning for PE ended up having the diagnosis, which is a pretty high prevalence. This emphasizes the dilemma of the PE workup - balancing a low-miss rate in this life-threatening diagnosis with risk of unnecessary imaging.

Rolling the Dimer Dice
This was a systematic review of 1,585 patients from 4 studies. They initially looked at 4,870 titles/abstracts, but an overwhelming majority of these studies did not meet their strict inclusion criteria: All studies had to use imaging as the reference standard. Among the studies meeting criteria, there was a degree of heterogeneity in type/threshold of D-dimer test, clinical prediction rule utilized, and types of CT scanners. This limits the inferences that can be made from this.

There was a wide confidence interval found in the sensitivity of D-dimer in the low-risk Geneva group (100% SN, 95% CI 61-100). So we take that 100% with a degree of skepticism. Meanwhile, the Wells non-high risk group (0-4) had a much narrower CI in the <65yo group (100% SN, 95% CI 97-100), with the best specificity between the groups (50% SP, 95% CI 45-55). The CI were wider in the Wells non-high risk group as age went up, and the specificity dropped. This could be addressed by age-adjusted D-dimer, but the authors did not include the results from that study. Bottom line, take this systematic review with a grain of salt, but it does provide decent support for utilization of D-dimer in Wells non-high risk group patients <65yo.

Update: D-dimer Test for Excluding the Diagnosis of Pulmonary Embolism.  Ann Emerg Med. 2017 Sep;70(3):e31-e32. doi: 10.1016/j.annemergmed.2016.12.012. Epub 2017 Mar 25.

Original Cochrane Review: Crawford F, Andras A, Welch K, et al. D-dimer test for excluding the diagnosis of pulmonary embolism. Cochrane Database Syst Rev. 2016;(8):CD010864

Peer reviewed by Clay Smith, MD.

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