Marc Righini1, Josien Van Es2, Paul L Den Exter3, Pierre-Marie Roy4, Franck Verschuren5, Alexandre Ghuysen6, Olivier T Rutschmann7, Olivier Sanchez8, Morgan Jaffrelot9, Albert Trinh-Duc10, Catherine Le Gall11, Farès Moustafa12, Alessandra Principe13, Anja A Van Houten14, Marije Ten Wolde15, Renée A Douma2, Germa Hazelaar16, Petra M G Erkens17, Klaas W Van Kralingen18, Marco J J H Grootenboers19, Marc F Durian20, Y Whitney Cheung15, Guy Meyer8, Henri Bounameaux1, Menno V Huisman3, Pieter W Kamphuisen21, Grégoire Le Gal22. 1. Division of Angiology and Hemostasis, Geneva University Hospital, Geneva, Switzerland. 2. Department of Vascular Medicine, Amsterdam Medical Center, Amsterdam, the Netherlands. 3. Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands. 4. Emergency Department, Centre Hospitalier Universitaire d'Angers, L'Université Nantes Angers Le Mans, Angers, France. 5. Cliniques Universitaires Saint-Luc, Bruxelles, Belgium. 6. Liège University Hospital, Liège, Belgium. 7. Emergency Department, Geneva University Hospital, Geneva, Switzerland. 8. Hôpital Européen Georges-Pompidou, Paris, France. 9. Emergency Department, Brest University Hospital, Brest, France. 10. Centre Hospitalier d'Agen, Agen, France. 11. Centre Hospitalier d'Argenteuil, Argenteuil, France. 12. Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France. 13. Centre Hospitalier de Morlaix, Morlaix, France. 14. Department of Internal Medicine, Maasstad Hospital, Rotterdam, the Netherlands. 15. Department of Internal Medicine, Flevoziekenhuis Hospital, Almere, the Netherlands. 16. Rijnstate Hospital, Arnhem, the Netherlands. 17. Maastricht University Medical Center, Maastricht, the Netherlands. 18. Van Weel-Bethesda Hospital, Dirksland, the Netherlands. 19. Amphia Hospital, Breda, the Netherlands. 20. Department of Hematology, Erasmus University Medical Center, Rotterdam, the Netherlands. 21. Department of Vascular Medicine, University Medical Center Groningen, Groningen, the Netherlands. 22. Ottawa Health Research Institute, Ottawa, Canada23Centre d'Investigations Cliniques, Université de Brest, Brest, France.
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.
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: Aiham Qdaisat; Rawan Al Soud; Carol C Wu; Cristhiam M Rojas Hernandez; Jieli Li; Qing H Meng; Hikmat Abdel-Razeq; Sai-Ching Jim Yeung Journal: Haematologica Date: 2019-01-10 Impact factor: 9.941
Authors: Giorgio Costantino; Martin H Ruwald; James Quinn; Carlos A Camargo; Frederik Dalgaard; Gunnar Gislason; Tadahiro Goto; Kohei Hasegawa; Padma Kaul; Nicola Montano; Anna-Karin Numé; Antonio Russo; Robert Sheldon; Monica Solbiati; Benjamin Sun; Giovanni Casazza Journal: JAMA Intern Med Date: 2018-03-01 Impact factor: 21.873