If you include D-dimer as part of your practice to exclude pulmonary embolism, you’re probably already aware background levels gradually increase with age. This results in further deterioration of the already poor specificity. Happily, this publication in JAMA demonstrates it’s probably safe to gradually increase your cut-off level for D-dimer with age without sacrificing sensitivity.
These authors enrolled 3,324 patients in a cohort with ultimate prevalence for PE of 19.0%. Of these, 2,898 fell into the “pulmonary embolism unlikely” group and underwent D-dimer testing. 817 met the traditional D-dimer <500 μg/L cut-off and no CTA was performed. An additional 337 patients met their “age-adjusted cutoff” – “10 x patient age” for those aged greater than 50 years. Only one patient with a negative D-dimer met their final adjudicated outcome of eventual venous thromboembolism. The authors, therefore, conclude this strategy of age-adjusted D-dimer cut-off is safe.
However, a handful of patients were lost to follow-up, and the confidence interval for 3-month VTE, considering the sample size, ranges from 0.1-1.7% in their age-adjusted cohort. Additionally, 7 patients died and 7 patients were evaluated for suspected VTE during the follow-up period. Only 1 was judged by their 3 experts to have been due to VTE, but this consensus measure for their primary outcome could have profound effects on their ultimate conclusion. Six different D-dimer assays were also used across their multi-center study, which hinders external generalizability.
But, in the end, it’s probably reasonable. The harms and costs secondary to testing and treating false-positives and small VTE still likely outweigh any additional misses through this strategy. Considering this comes from JAMA, it’s likely defensible in the face of peer-review to begin using age-adjusted cut-offs immediately.
“Age-Adjusted D-Dimer Cutoff Levels to Rule Out Pulmonary Embolism”