Under Review Journal Club Article
Righini M, Van Es J,Den Exter PL, et al.. "Age-Adjusted D-Dimer Cutoff Levels to Rule Out Pulmonary Embolism". JAMA. 2014. 311(11):1117-1124.
PubMed Full text

Clinical Question

Is an age-adjusted D-dimer cutoff (age × 10 in patients >50 yrs) associated with an increased diagnostic yield of D-dimer in elderly patients with suspected PE?


An age-adjusted D-dimer in combination with pretest probability was associated with a larger number of patients in whom PE could be considered ruled out with a low likelihood of subsequent clinical venous thromboembolism.

Major Points

  • An age-adjusted D-dimer is associated with a greater number of patients in whom PE can be safely ruled out

Study Design

A multicenter, multinational, prospective management outcome study in 19 centers in Belgium, France, the Netherlands, and Switzerland between January 1, 2010, and February 28, 2013.


Patient Demographics

  • Women: 56.8%
  • Age: median 63 yrs (53-74 1st/3rd quartile)
  • H/O VTE: 14.0%
  • Active malignancy: 12.9%
  • Surgery within 1 month: 11.8%
  • Estrogen use: 5.5%
  • Chest pain: 48.3%
  • Dyspnea: 62.9%
  • Syncope: 7.9%
  • Hemoptysis: 4.1%
  • Heart rate: mean 87.1 beats/min
  • Respiratory rate: mean 19.2 breaths/min

Inclusion Criteria

  • Clinical suspicion of PE
    • Acute onset SOB
    • Worsening SOB
    • Chest pain without obvious etiology

Exclusion Criteria

  • PE suspicion raised more than 24 hrs after admission
  • Taking anticoagulant therapy
  • Inability to receive a CTPA study
  • Life expectancy <3 mos
  • Ongoing pregnancy
  • Unable to follow up


  • Risk assessed with revised Geneva score or Wells
  • Highly sensitive D-dimer measurement
  • CTPA
  • Participants with a D-dimer value between the conventional cutoff of 500 μg/L and their age-adjusted cutoff did not undergo CTPA and were left untreated and formally followed-up for a 3-month period


Primary Outcome

  • Failure rate of the diagnostic strategy
  • Conventional 500 μg/L cut off lead to 1 nonfatal PE in 810 patients (0.1% [0.0%-0.7%])
  • Age-adjusted cut off lead to 1 nonfatal PE in 331 patients (0.3% [0.1%-1.7%])

Secondary Outcomes

  • Proportion of patients with a low-intermediate probability and a D-dimer between 500 μg/L and their age-adjusted cutoff


  • Age-adjusted cutoff resulted in an 11.6% absolute increase [10.5%-12.9%] or a 41.2% relative increase [31.3%-52.0%] in the proportion of negative D-dimer results

Subgroup analysis

  • Elderly patients, defined as patients 75 years or older
  • None of the 195 patients had a confirmed VTE during follow-up (0.0% [95% CI, 0.0%-1.9%])


Criticisms & Further Discussion

  • The assays used had a cutoff of 500 ug/L; take caution in applying age x 10 until you know your hospitals assay
  • R.E.B.E.L EM
    • 2 different pretest probability scores and 6 different d-dimer assays were used
    • Not a randomized clinical control study, so there was no control group
    • 7 patients were deceased in the > 500 ug/L and < age adjusted cutoff d-dimer, but only one had an autopsy to confirm diagnosis, therefore hard to exclude PE as the cause of death
    • Prevalence of PE was higher than what is cited in most North American studies, but the same rate as European studies
    • Patient follow up was not with the gold standard CTPA

External Links

R.E.B.E.L EM: Age-Adjusted D-dimer


  • Swiss National Research Foundation grant 32003B-130863
  • International Society on Thrombosis and Haemostasis 2007 presidential fund
  • Dutch Thrombosis Foundation grant 2010-5
  • Projets Hospitaliers de Recherche Clinique, French Ministry of Health grant PHRC 2011 08-01
  • France, the study was sponsored by Direction de la Recherche Clinique et de l’Innovation, Brest University Hospital