title: Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01134068.
authors.affiliation: Division of Angiology and Hemostasis, Geneva University Hospital, Geneva, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Righini
authors.affiliation: Department of Vascular Medicine, Amsterdam Medical Center, Amsterdam, the Netherlands.
authors.forename: Josien
authors.initials: J
authors.lastname: Van Es
authors.affiliation: Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Den Exter
authors.affiliation: Emergency Department, Centre Hospitalier Universitaire d'Angers, L'Université Nantes Angers Le Mans, Angers, France.
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Roy
authors.affiliation: Cliniques Universitaires Saint-Luc, Bruxelles, Belgium.
authors.forename: Franck
authors.initials: F
authors.lastname: Verschuren
authors.affiliation: Liège University Hospital, Liège, Belgium.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Ghuysen
authors.affiliation: Emergency Department, Geneva University Hospital, Geneva, Switzerland.
authors.forename: Olivier T
authors.initials: OT
authors.lastname: Rutschmann
authors.affiliation: Hôpital Européen Georges-Pompidou, Paris, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Sanchez
authors.affiliation: Emergency Department, Brest University Hospital, Brest, France.
authors.forename: Morgan
authors.initials: M
authors.lastname: Jaffrelot
authors.affiliation: Centre Hospitalier d'Agen, Agen, France.
authors.forename: Albert
authors.initials: A
authors.lastname: Trinh-Duc
authors.affiliation: Centre Hospitalier d'Argenteuil, Argenteuil, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Le Gall
authors.affiliation: Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France.
authors.forename: Farès
authors.initials: F
authors.lastname: Moustafa
authors.affiliation: Centre Hospitalier de Morlaix, Morlaix, France.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Principe
authors.affiliation: Department of Internal Medicine, Maasstad Hospital, Rotterdam, the Netherlands.
authors.forename: Anja A
authors.initials: AA
authors.lastname: Van Houten
authors.affiliation: Department of Internal Medicine, Flevoziekenhuis Hospital, Almere, the Netherlands.
authors.forename: Marije
authors.initials: M
authors.lastname: Ten Wolde
authors.affiliation: Department of Vascular Medicine, Amsterdam Medical Center, Amsterdam, the Netherlands.
authors.forename: Renée A
authors.initials: RA
authors.lastname: Douma
authors.affiliation: Rijnstate Hospital, Arnhem, the Netherlands.
authors.forename: Germa
authors.initials: G
authors.lastname: Hazelaar
authors.affiliation: Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: Petra M G
authors.initials: PM
authors.lastname: Erkens
authors.affiliation: Van Weel-Bethesda Hospital, Dirksland, the Netherlands.
authors.forename: Klaas W
authors.initials: KW
authors.lastname: Van Kralingen
authors.affiliation: Amphia Hospital, Breda, the Netherlands.
authors.forename: Marco J J H
authors.initials: MJ
authors.lastname: Grootenboers
authors.affiliation: Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands.
authors.forename: Marc F
authors.initials: MF
authors.lastname: Durian
authors.affiliation: Department of Internal Medicine, Flevoziekenhuis Hospital, Almere, the Netherlands.
authors.forename: Y Whitney
authors.initials: YW
authors.lastname: Cheung
authors.affiliation: Hôpital Européen Georges-Pompidou, Paris, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Meyer
authors.affiliation: Division of Angiology and Hemostasis, Geneva University Hospital, Geneva, Switzerland.
authors.forename: Henri
authors.initials: H
authors.lastname: Bounameaux
authors.affiliation: Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Menno V
authors.initials: MV
authors.lastname: Huisman
authors.affiliation: Department of Vascular Medicine, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Pieter W
authors.initials: PW
authors.lastname: Kamphuisen
authors.affiliation: Ottawa Health Research Institute, Ottawa, Canada23Centre d'Investigations Cliniques, Université de Brest, Brest, France.
authors.forename: Grégoire
authors.initials: G
authors.lastname: Le Gal
mesh_terms: D000208:Acute Disease; D000367:Age Factors; D000368:Aged; D000792:Angiography; D003951:Diagnostic Errors; D004636:Emergency Service, Hospital; D005060:Europe / Q000453:epidemiology; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis*; D006801:Humans; D008297:Male; D010045:Outpatients; D015995:Prevalence; D011336:Probability; D011446:Prospective Studies; D011655:Pulmonary Embolism / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology; D012016:Reference Values; D012306:Risk; D012680:Sensitivity and Specificity; D054556:Venous Thromboembolism / Q000097:blood / Q000453:epidemiology*
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D