title: Questioning the use of an age-adjusted D-dimer threshold to exclude venous thromboembolism: analysis of individual patient data from two diagnostic studies.
abstract: Essentials It is unclear if raising the D-dimer level to exclude venous thrombosis in older patients is valid. We compared this 'age-adjusted' strategy with other ways of interpreting D-dimer results. A non-age adjusted increase, and using higher thresholds in younger patients, was just as accurate. Age-adjustment of D-dimer thresholds does not appear to be appropriate. Click to hear Prof. le Gal's presentation on controversies in venous thromboembolism diagnosis SUMMARY: Background Using a progressively higher D-dimer level to exclude venous thromboembolism (VTE) with increasing age has been proposed but is not well validated. Objective To determine whether it is appropriate to use a progressively higher D-dimer level to exclude VTE with increasing age. Patients/methods We analyzed clinical data and blood samples from 1649 patients with a first suspected deep vein thrombosis or pulmonary embolism. We compared the negative predictive values (NPVs) for VTE, and the proportions of patients with a negative D-dimer result, by using three D-dimer interpretation strategies: a progressively higher D-dimer threshold with increasing age (age-adjusted strategy); the same higher D-dimer threshold in all patients (mean D-dimer strategy); and a progressively higher D-dimer threshold with decreasing age (inverse age-adjusted strategy). Results The NPV with the age-adjusted strategy (99.6%; 95% confidence interval [CI] 99.0-99.9%) was not different from that with the mean D-dimer strategy (99.7%; 95% CI 99.0-99.9%) or that with the inverse age-adjusted strategy (99.8%; 95% CI 99.1-99.9%). The proportion of patients with a negative result with the age-adjusted strategy (50.9%; 95% CI 48.5-53.4%) was not different from the proportion of patients with a negative result with the mean D-dimer strategy (51.7%; 95% CI 49.3-54.1%) or with the inverse age-adjusted strategy (49.5%; 95% CI 47.1-51.9%). Conclusions Our analysis does not support the use of a progressively higher D-dimer level to exclude VTE with increasing age.
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada. takachla@ualberta.ca.|Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. takachla@ualberta.ca.
authors.forename: S
authors.initials: S
authors.lastname: Takach Lapner
authors.affiliation: Ontario Clinical Oncology Group, Juravinski Hospital, Hamilton, Ontario, Canada.
authors.forename: J A
authors.initials: JA
authors.lastname: Julian
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.|Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada.
authors.forename: L-A
authors.initials: LA
authors.lastname: Linkins
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.|Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada.
authors.forename: S M
authors.initials: SM
authors.lastname: Bates
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada.|Thrombosis and Atherosclerosis Research Institute, McMaster University, Hamilton, Ontario, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Kearon
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D011237:Predictive Value of Tests; D011336:Probability; D011446:Prospective Studies; D011655:Pulmonary Embolism / Q000097:blood*; D012016:Reference Values; D015203:Reproducibility of Results; D054556:Venous Thromboembolism / Q000097:blood*; D020246:Venous Thrombosis / Q000097:blood*
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D
keywords: D-dimer; diagnosis; humans; sensitivity and specificity; venous thromboembolism