title: Is stand-alone D-dimer testing safe to rule out acute pulmonary embolism?
abstract: Essentials A stand-alone D-dimer below 750 μg/L has been proposed to rule out acute pulmonary embolism (PE). This was a post-hoc analysis on data from 6 studies comprising 7268 patients with suspected PE. The negative predictive value of a D-dimer <750 μg/L ranged from 79% to 96% in various subgroups. Stand-alone D-dimer testing seems to be unsafe to rule out PE in all patients.
  
  
  
  Background Recently, stand-alone D-dimer testing at a positivity threshold of 750 μg L-1has been proposed as a safe and efficient approach to rule out acute pulmonary embolism (PE), without additional imaging, but this approach needs validation. Objectives To evaluate stand-alone D-dimer testing at a positivity threshold of 750 μg L-1to rule out PE. Methods Individual data from 7268 patients with suspected PE previously enrolled in six prospective management studies were used. Patients were assessed by the Wells rule followed by quantitative D-dimer testing in those with a 'PE unlikely' score. Patients were classified post hoc as having a negative (< 750 μg L-1) or positive (≥ 750 μg L-1) D-dimer. Using a one-stage meta-analytic approach, the negative predictive value (NPV) of stand-alone D-dimer testing was evaluated overall and in different risk subgroups. Results The pooled incidence of PE was 23% (range, 13-42%). Overall, 44% of patients had a D-dimer < 750 μg L-1, of whom 2.8% were diagnosed with PE at baseline or during 3-month follow-up (NPV, 97.2%; 95% confidence interval [CI], 94.9-98.5). The NPV was highest in patients with a low probability of PE according to the Wells rule (99.2%; 95% CI, 98.6-99.5%) and lowest in those with a high probability of PE (79.3%; 95% CI, 53.0-92.8%). The NPVs in patients with active cancer, patients with previous venous thromboembolism and inpatients were 96.2% (95% CI, 85.6-99.1%), 94.7% (95% CI, 88.6-97.6%) and 92.7% (95% CI, 79.3-97.7%), respectively. Conclusions Our findings suggest that stand-alone D-dimer testing at a positivity threshold of 750 μg L-1is not safe to rule out acute PE.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: N
authors.initials: N
authors.lastname: van Es
authors.affiliation: Department of Thrombosis and Haemostasis, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: van der Hulle
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: H R
authors.initials: HR
authors.lastname: Büller
authors.affiliation: Department of Thrombosis and Haemostasis, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: F A
authors.initials: FA
authors.lastname: Klok
authors.affiliation: Department of Thrombosis and Haemostasis, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: M V
authors.initials: MV
authors.lastname: Huisman
authors.affiliation: Service of Anesthesiology, Hospital MD Anderson Cancer Center, Madrid, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Galipienzo
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.|Department of Medical, Oral and Biotechnological Sciences, Gabriele D'Annunzio University, Chieti, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Di Nisio
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis*; D006439:Hemodynamics; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011336:Probability; D011446:Prospective Studies; D011655:Pulmonary Embolism / Q000097:blood* / Q000175:diagnosis* / Q000453:epidemiology; D012306:Risk; D054556:Venous Thromboembolism / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D
keywords: D-dimer; diagnosis; pulmonary embolism; sensitivity and specificity; venous thromboembolism