Diagnosis of PE with D-Dimer Adjusted to Clinical Probability- A game changer!

Intern, “the D-dimer just came back at 0.6… what should I do?”

Me, “… faaaaaaaaaaaaaaaaaaaaaaaaarrrrrrrk!”

Fortunately, this study is probably a game changer.

These Canadian’s conducted a prospective study in which PE was considered to be ruled out if the pretest clinical suspicion was low (Well’s score0-4) and a D-dimer of less than 1.0mg/L or if the clinical suspicion was moderate (Well’s score 4.5-6) and D-dimer less than 0.5mg/L.

Just over two thousand patients were enrolled. Their overall rate of PE was 7.4%.

Of the 1325 patients with low or moderate clinical suspicion for PE and a negative D-dimer (as above), NONE (95%CI 0.0 to 0.29%) of them had venous thromboembolism during the 3-month follow up.   

This is amazing.

Once again, two-thirds of all patients were excluded from imaging and the diagnostic performance of this strategy was perfect.

Furthermore, this publication from the NEJM is one in line of papers supporting the notion of adjusting D-dimer thresholds. Consistency in the literature is reassuring.

Slam dunk?

Ok… no studies are perfect. What were the two major limitations?

The quality of a study looking at diagnostic performance of a test is only as good its gold standard. Unfortunately, patients that were ruled out by this strategy did not have definitive imaging. This study relied on 3-month follow up (sometimes by telephone) and may have led to the underdiagnosis of PE.

Secondly, there were 34 deaths during follow-up.

Yikes!

But they claim, “no deaths were attributed by the central adjudication committee to pulmonary embolism.” Table S5 in the supplementary appendix shows that most died of cancer or cardiovascular disease. I very much doubt many (if any) of the deaths had autopsy performed. We all know PE can be quite tricky to diagnose. I still wonder if some of these deaths were due to missed PE.

Despite these limitations, I still think adjusting D-dimer thresholds makes sense. And now it is supported by numerous studies published in high impact journals.

Intern, “the D-dimer just came back at 0.6… what should I do?”

Me, “Never order a D-dimer without asking me first!”

Oh… I meant, “send them home…” And hopefully they don’t die of “cancer.”

Covering:

Kearon C, de Wit, Parpia S, et al. Diagnosis of Pulmonary Embolism with D-dimer Adjusted to Clinical Probability. N Engl J Med 2019;381:2125-34. [link to article]