Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study.

Abstract

IMPORTANCE:

D-dimer measurement is an important step in the diagnostic strategy of clinically suspected acute pulmonary embolism (PE), but its clinical usefulness is limited in elderly patients.

OBJECTIVE:

To prospectively validate whether an age-adjusted D-dimer cutoff, defined as age × 10 in patients 50 years or older, is associated with an increased diagnostic yield of D-dimer in elderly patients with suspected PE.

DESIGN, SETTINGS, AND PATIENTS:

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.

INTERVENTIONS:

All consecutive outpatients who presented to the emergency department with clinically suspected PE were assessed by a sequential diagnostic strategy based on the clinical probability assessed using either the simplified, revised Geneva score or the 2-level Wells score for PE; highly sensitive D-dimer measurement; and computed tomography pulmonary angiography (CTPA). Patients 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.

MAIN OUTCOMES AND MEASURES:

The primary outcome was the failure rate of the diagnostic strategy, defined as adjudicated thromboembolic events during the 3-month follow-up period among patients not treated with anticoagulants on the basis of a negative age-adjusted D-dimer cutoff result.

RESULTS:

Of the 3346 patients with suspected PE included, the prevalence of PE was 19%. Among the 2898 patients with a nonhigh or an unlikely clinical probability, 817 patients (28.2%) had a D-dimer level lower than 500 µg/L (95% CI, 26.6%-29.9%) and 337 patients (11.6%) had a D-dimer between 500 µg/L and their age-adjusted cutoff (95% CI, 10.5%-12.9%). The 3-month failure rate in patients with a D-dimer level higher than 500 µg/L but below the age-adjusted cutoff was 1 of 331 patients (0.3% [95% CI, 0.1%-1.7%]). Among the 766 patients 75 years or older, of whom 673 had a nonhigh clinical probability, using the age-adjusted cutoff instead of the 500 µg/L cutoff increased the proportion of patients in whom PE could be excluded on the basis of D-dimer from 43 of 673 patients (6.4% [95% CI, 4.8%-8.5%) to 200 of 673 patients (29.7% [95% CI, 26.4%-33.3%), without any additional false-negative findings.

CONCLUSIONS AND RELEVANCE:

Compared with a fixed D-dimer cutoff of 500 µg/L, the combination of pretest clinical probability assessment with age-adjusted D-dimer cutoff 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.

TRIAL REGISTRATION:

clinicaltrials.gov Identifier: NCT01134068.

• Authors: Marc Righini, Josien Van Es, Paul L Den Exter, Pierre-Marie Roy, Franck Verschuren, Alexandre Ghuysen, Olivier T Rutschmann, Olivier Sanchez, Morgan Jaffrelot, Albert Trinh-Duc, Catherine Le Gall, Farès Moustafa, Alessandra Principe, Anja A Van Houten, Marije Ten Wolde, Renée A Douma, Germa Hazelaar, Petra M G Erkens, Klaas W Van Kralingen, Marco J J H Grootenboers, Marc F Durian, Y Whitney Cheung, Guy Meyer, Henri Bounameaux, Menno V Huisman, Pieter W Kamphuisen, Grégoire Le Gal
• Journal: JAMA (JAMA) Vol. 311 Issue 11 Pg. 1117-24 (Mar 19 2014) ISSN: 1538-3598 [Electronic] United States
• PMID: 24643601 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't, Validation Study)

Chemical References

• Fibrin Fibrinogen Degradation Products
• fibrin fragment D

Topics

• Acute Disease
• Age Factors
• Aged
• Angiography
• Diagnostic Errors
• Emergency Service, Hospital
• Europe (epidemiology)
• Female
• Fibrin Fibrinogen Degradation Products (analysis)
• Humans
• Male
• Outpatients
• Prevalence
• Probability
• Prospective Studies
• Pulmonary Embolism (blood, diagnosis, epidemiology)
• Reference Values
• Risk
• Sensitivity and Specificity
• Venous Thromboembolism (blood, epidemiology)