Pulmonary embolism is a commonly-investigated diagnosis in the world of emergency department risk stratification — the presentation of these patients is varied, the ultimate impact on patients of the disease entity itself is questionable when it comes to the less sick end of the spectrum, and the tools we have for diagnosis are associated with significant amounts of radiation and contrast. However, in a practice environment with a low tolerance for missed diagnoses (however questionable the risk:benefit balance of the intervention that would have been performed), we continue to strive to balance the risks and costs of diagnostic testing with the very real risk of progressive disease.
The D-Dimer level is a test used in patients with a low to moderate pretest probability of DVT or PE (and possibly aortic dissection?) — if negative, it will virtually rule out PE, and can help you avoid further testing with CT pulmonary angiography. If positive, further testing is required. So why do emergency physicians hate the D-Dimer? Because while elevation in D-Dimer levels is sensitive for pulmonary embolism or DVT, it is not specific — particularly with cutoff levels of ~ 500 ng/dL, which is the conventional cutoff for a positive test. Elevated D-Dimer levels occur for a multitude of reasons, including liver disease, inflammation, malignancy, trauma, pregnancy, and– most complicating of all– advanced age.
The first of the studies I read this weekend, the ADJUST-PE study, a group of authors had previously retrospectively derived and valid the value of a progressive D-Dimer cutoff adjusted to age in 1712 patients — the optimal age-adjusted cutoff was defined as patient’s age multiplied by 10 in patients 50 years or older. The ADJUST-PE study represented their attempt to prospectively validate the adjustment and to assess its impact on patients in real life. In this multi-center study which enrolled 3324 patients, the age adjusted D-Dimer cut off did very well — only one patient who had a D-Dimer between 500 ng/dL and their age-adjusted cutoff (in other words, someone who would have gotten scanned if they weren’t using the new tool) was found at three month follow up to have a PE, and this was non-fatal. The age adjusted level allowed for safe discharge of patients that might otherwise have been exposed to the costs/potential harms associated with CTPA or treatment of non-hemodynamically significant emboli.
The second study takes the same approach and retrospectively applies the cutoff to 31,094 suspected pulmonary embolism patients presenting to an emergency department in the community. They report data for all ED visits for Kaiser Permanente Southern California members older than 50 years, from 2008 to 2013, who received a D-dimer test after presenting with a chief complaint related to possible PE such as chest pain or dyspnea (due to their focus on PE rather than DVT). The authors excluded patients who underwent ultrasound imaging for DVT for the same reason. What they found was a sensitivity of 92.9% and a specificity of 63.9% for the age-adjusted D-Dimer threshold applied to this population — this compares to 98.0% and 54.4% for the traditional threshold of 500 ng/dL. This is not unsurprising — what I thought was interesting about the second paper was its expansion of the discussion of this testing strategy to include estimates for other harms beyond symptomatic PE that might be missed — specifically, they discuss the incidence of contrast-induced nephropathy, and how changes in testing strategies translate into potential benefits there that may outweigh the harms done by missing clots. These are statistical models, and need to be taken with a grain of salt, but they predict that “using an age-adjusted D-dimer threshold would miss or delay diagnosis of 26 more pulmonary embolisms than the current standard, but it would prevent 322 cases of contrast- induced nephropathy, 29 cases of severe renal failure, and 19 deaths related to contrast-induced nephropathy in this sample.”
So what will I do with this information? Probably try for better shared decision making and try to avoid CTPA in patients with D-Dimers below the age-adjusted cutoff. I think sharing these numbers with our patients in a comprehensible way, and talking to them about the potential harms associated with testing is the best way forward– this will require further work in terms of identifying the best way to communicate these risks and odds to patients, and as always, trying to balance advocacy for patients, and our ultimate goal of keeping them safe, alive and functional, with the fear of missing a diagnosis or sending someone home with a nebulous non-diagnosis and the possibility of clinical deterioration.