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Age-adjusted D-dimer cutoff levels more accurate for PE diagnosis (ADJUST-PE)

Clinical Question:
Is the age-adjusted D-dimer cutoff level accurate for diagnosing pulmonary embolus?

Bottom Line:
Using the age-adjusted D-dimer cutoff level (< 500 ug/L in patients younger than 50 years and < age multiplied by 10 in patients 50 years or older) combined with probability assessment using the Geneva score or Wells score accurately ruled out the diagnosis of pulmonary embolus (PE) in the emergency department and was associated with a low likelihood of subsequent symptomatic venous thromboembolic events (VTEs). In addition, the age-adjusted D-dimer cutoff level results in an increased proportion of patients in whom the diagnosis could be accurately excluded, thus avoiding unnecessary and costly additional imaging testing. (LOE = 1b)

Righini M, Van Es J, Den Exter PL, et al. Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism. The ADJUST-PE study. JAMA 2014;311(11):1117-1124.  [PMID:24643601]

Study Design:
Diagnostic test evaluation


Emergency department

D-dimer levels increase with age and thus may affect the clinical usefulness of the test. These investigators wished to prospectively validate the value of a progressive D-dimer cutoff adjusted to patient's age multiplied by 10 in patients 50 years or older. Eligible patients included consecutive outpatients presenting to the emergency department of participating hospitals with clinical suspicion of PE without another obvious etiology. Previously validated clinical decision tools (Geneva or Wells) assessed the initial clinical probability of PE and patients with a high or a likely probability proceeded directly to CT pulmonary angiography (CTPA). Patients with a low/intermediate or unlikely clinical probability underwent D-dimer testing. Patients with a positive D-dimer result (> 500 ug/L in patients younger than 50 years, and > age multiplied by 10 in patients 50 years or older) also underwent CTPA. Patients with a positive CTPA result received anticoagulant therapy. Individuals who were masked to the criteria used to rule out PE at inclusion reviewed the medical records and adjudicated all suspected VTEs and deaths. Complete follow-up occurred for 3 months. The authors note that the false negative rate of pulmonary angiography for diagnosing PE is 3%, so 3% is the accepted criterion for the validation of diagnostic strategies for PE. Of the 3324 eligible patients, clinical probability was not high in 2898 (87.2%). Of these, 1154 (39.8%) patients had a negative D-dimer result as defined by the study criteria. The use of the age-adjusted cutoff resulted in an 11.6% absolute increase in the proportion of negative D-dimer results. The overall prevalence of PE in the study was 19.0%. During the 3-month follow-up period, of the 817 patients with a D-dimer level lower than 500 ug/L, only one adjudicated confirmed nonfatal PE occurred (0.1%; 95% CI, 0.0% - 0.7%). Of the 337 patients with a D-dimer level between 500 ug/L and their age-adjusted cutoff, only one adjudicated confirmed nonfatal PE occurred (0.3%, 0.1% - 1.7%). In the 1539 patients with an elevated D-dimer level or with a high or likely clinical probability but with a negative CTPA result, 7 adjudicated confirmed VTEs occurred, resulting in a false negative CTPA rate of 0.5% (0.2% - 1.0%). Of the 195 patients 75 years or older with a negative D-dimer result, none had a confirmed VTE during follow-up (0.0%; 0.0% - 1.9%).


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