Consideration of these outdated harm estimates forms the basis of the argument made by Kline et al in their proposal to double the D-dimer threshold.⁴ In a prospective, observational evaluation of 678 patients evaluated for PE, the overall miss rate in a “PE unlikely” population of Wells ≤4 or Revised Geneva Score ≤6 was 3.8 percent at a cutoff of 500 ng/mL. Increasing this threshold to 1,000 ng/mL increased the miss rate to 5.4 percent in this cohort, but 10 of the 11 missed PEs were subsegmental and none had concomitant deep venous thrombosis. Considering the current American College of Chest Physicians guidelines suggest clinical surveillance over anticoagulation for properly selected patients with subsegmental PE, the clinical importance of these “false negatives” is questionable.

While the argument made by Kline and colleagues is solely theoretical, at least two other articles describe putting this concept into practice. The Kaiser Permanente Hawaii region describes increasing the D-dimer threshold from 400 ng/mL to 1,000 ng/mL as part of an institutional effort to reduce unnecessary testing.⁵ Its retrospective review of patients evaluated for PE found zero missed from a cohort of 182 low- and intermediate-risk patients. Subsequently, after practice change, ongoing quality assessment did not detect any missed PEs in a similar cohort of 47 patients using 1,000 ng/mL as a threshold.

Finally, the second article prospectively describing practice using a threshold of 1,000 ng/mL comprises a Dutch effort directly following the Kline analysis.⁶ These authors performed their own retrospective and observational prospective analyses to clarify which elements of risk stratification conveyed the greatest risk with relation to pretest likelihood of PE.^7,8 Their resulting protocol, the YEARS algorithm, was then prospectively evaluated across 12 Dutch hospitals across almost two years. Their results were published in The Lancet in May.

Their algorithm dramatically simplifies the approach to risk stratification and testing. All patients considered for PE are tested using D-dimer. Patients with one of the three YEARS high-risk items—clinical signs of deep vein thrombosis, hemoptysis, and whether pulmonary embolism is the most likely diagnosis—could be excluded from further testing using the conventional cutoff of 500 ng/mL. Then patients without any of those high-risk features used a cutoff of 1,000 ng/mL.

In their cohort of 3,465 patients undergoing the protocol, rate of subsequent venous thromboembolism was nearly identical between those excluded from additional testing by variable D-dimer thresholds and those with the diagnosis excluded by CTPA. Of 1,633 non-anticoagulated patients in follow-up after a D-dimer below their specific threshold, only seven were ultimately diagnosed with PE in the following three months. Similarly, in follow-ups of 1,138 with negative CTPA results, eight patients were ultimately diagnosed. The face validity of nearly identical miss rates between imaging and non-imaging pathways lends substantial credibility to their algorithm.