Comparison of clinical probability-adjusted D-dimer and age-adjusted D-dimer interpretation to exclude venous thromboembolismFinancial support: There was no external funding for this study. The STA-Liatest D-Dimer assays used in this study were provided by Diagnostica Stago (Asnières, France) and D-dimer testing was performed by the Hemostasis Reference Laboratory (Hamilton, Ontario, Canada). Dr. Bates receives salary support as the Eli Lily Canada/May Cohen Chair in Women’s Health. Dr. Kearon is supported by an Investigator Award from the Heart & Stroke Foundation of Canada and the Jack Hirsh Professorship in Thromboembolism.
14 March 2017
Accepted after major revision: 21 June 2017
08 November 2017 (online)
Two new strategies for interpreting D-dimer results have been proposed: i) using a progressively higher D-dimer threshold with increasing age (age-adjusted strategy) and ii) using a D-dimer threshold in patients with low clinical probability that is twice the threshold used in patients with moderate clinical probability (clinical probability-adjusted strategy). Our objective was to compare the diagnostic accuracy of age-adjusted and clinical probability-adjusted D-dimer interpretation in patients with a low or moderate clinical probability of venous thromboembolism (VTE). We performed a retrospective analysis of clinical data and blood samples from two prospective studies. We compared the negative predictive value (NPV) for VTE, and the proportion of patients with a negative D-dimer result, using two D-dimer interpretation strategies: the age-adjusted strategy, which uses a progressively higher D-dimer threshold with increasing age over 50 years (age in years × 10 µg/L FEU); and the clinical probability-adjusted strategy which uses a D-dimer threshold of 1000 µg/L FEU in patients with low clinical probability and 500 µg/L FEU in patients with moderate clinical probability. A total of 1649 outpatients with low or moderate clinical probability for a first suspected deep vein thrombosis or pulmonary embolism were included. The NPV of both the clinical probability-adjusted strategy (99.7%) and the age-adjusted strategy (99.6%) were similar. However, the proportion of patients with a negative result was greater with the clinical probability-adjusted strategy (56.1% vs, 50.9%; difference 5.2%; 95% CI 3.5% to 6.8%). These findings suggest that clinical probability-adjusted D-dimer interpretation is a better way of interpreting D-dimer results compared to age-adjusted interpretation.
- 1 Di Nisio M, Squizzato A, Rutjes AW. et al. Diagnostic accuracy of D-dimer test for exclusion of venous thromboembolism: a systematic review. J Thromb Haemost 2007; 05: 296-304.
- 2 Douma RA, le Gal G, Sohne M. et al. Potential of an age adjusted D-dimer cut-off value to improve the exclusion of pulmonary embolism in older patients: a retrospective analysis of three large cohorts. Br Med J 2010; 340: c1475.
- 3 Righini M, Van Es J, Den Exter PL. et al. Age-adjusted D-dimer cutoff levels to rule out pulmonary embolism: the ADJUST-PE study. J Am Med Assoc 2014; 311: 1117-1124.
- 4 van Es N, van der Hulle T, van Es J. et al. Wells Rule and d-Dimer Testing to Rule Out Pulmonary Embolism: A Systematic Review and Individual-Patient Data Meta-analysis. Ann Intern Med 2016; 165: 253-261.
- 5 Takach Lapner S, Julian JA, Linkins LA. et al. Questioning Use of an Age-Adjusted D-Dimer Threshold to Exclude Venous Thromboembolism: Analysis of Individual Patient Data from Two Diagnostic Studies. J Thromb Haemost. 2016 Epub ahead of print.
- 6 Schouten HJ, Geersing GJ, Koek HL. et al. Diagnostic accuracy of conventional or age adjusted D-dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and meta-analysis. Br Med J 2013; 346: f2492.
- 7 Righini M, Goehring C, Bounameaux H. et al. Effects of age on the performance of common diagnostic tests for pulmonary embolism. Am J Med 2000; 109: 357-361.
- 8 Kline JA, Hogg MM, Courtney DM. et al. D-dimer threshold increase with pretest probability unlikely for pulmonary embolism to decrease unnecessary computerized tomographic pulmonary angiography. J Thromb Haemost 2012; 10: 572-581.
- 9 Linkins LA, Bates SM, Ginsberg JS. et al. Use of different D-dimer levels to exclude venous thromboembolism depending on clinical pretest probability. J Thromb Haemost 2004; 02: 1256-1260.
- 10 Kabrhel C, Courtney MD, Camargo Jr CA. et al. Potential impact of adjusting the threshold of the quantitative D-dimer based on pretest probability of acute pulmonary embolism. Acad Emerg Med 2009; 16: 325-332.
- 11 van Es J, Beenen LF, Douma RA. et al. A simple decision rule including D-dimer to reduce the need for computed tomography scanning in patients with suspected pulmonary embolism. J Thromb Haemost 2015; 13: 1428-1435.
- 12 Geersing GJ, Zuithoff NP, Kearon C. et al. Exclusion of deep vein thrombosis using the Wells rule in clinically important subgroups: individual patient data meta-analysis. Br Med J 2014; 348: g1340.
- 13 Ceriani E, Combescure C, Le Gal G. et al. Clinical prediction rules for pulmonary embolism: a systematic review and meta-analysis. J Thromb Haemost 2010; 08: 957-970.
- 14 Linkins LA, Bates SM, Lang E. et al. Selective D-dimer testing for diagnosis of a first suspected episode of deep venous thrombosis: a randomized trial. Ann Intern Med 2013; 158: 93-100.
- 15 Bates SM, Takach Lapner S, Douketis JD. et al. Rapid quantitative D-dimer to exclude pulmonary embolism: a prospective cohort management study. J Thromb Haemost 2016; 14: 504-509.
- 16 Kearon C, Ginsberg JS, Douketis J. et al. An evaluation of D-dimer in the diagnosis of pulmonary embolism: a randomized trial. Ann Intern Med 2006; 144: 812-821.
- 17 Hendriksen JM, Geersing GJ, Lucassen WA. et al. Diagnostic prediction models for suspected pulmonary embolism: systematic view and independent external validation in primary care. Br Med J 2015; 351: h4438.
- 18 Geersing GJ, Erkens PM, Lucassen WA. et al. Safe exclusion of pulmonary embolism using the Wells rule and qualitative D-dimer testing in primary care: prospective cohort study. Br Med J 2012; 345: e6564.
- 19 Wells PS, Hirsh J, Anderson DR. et al. Accuracy of clinical assessment of deep-vein thrombosis. Lancet 1995; 345: 1326-1330.
- 20 Agresti A, Min Y. Simple improved confidence intervals for comparing matched proportions. Stat Med 2005; 24: 729-740.
- 21 Leisenring W, Alonzo T, Pepe MS. Comparisons of predictive values of binary medical diagnostic tests for paired designs. Biometrics 2000; 56: 345-351.
- 22 Woller SC, Stevens SM, Adams DM. et al. Assessment of the safety and efficiency of using an age-adjusted D-dimer threshold to exclude suspected pulmonary embolism. Chest 2014; 146: 1444-1451.
- 23 Yamaki T, Nozaki M, Sakurai H. et al. Combined use of pretest clinical probability score and latex agglutination D-dimer testing for excluding acute deep vein thrombosis. J Vasc Surg 2009; 50: 1099-1105.
- 24 Fuchs E, Asakly S, Karban A. et al. Age-Adjusted Cutoff D-Dimer Level to Rule Out Acute Pulmonary Embolism: A Validation Cohort Study. Am J Med 2016; 129: 872-878.
- 25 Righini M, Aujesky D, Roy PM. et al. Clinical usefulness of D-dimer depending on clinical probability and cutoff value in outpatients with suspected pulmonary embolism. Arch Intern Med 2004; 164: 2483-2487.
- 26 Kelly J, Hunt BJ. A clinical probability assessment and D-dimer measurement should be the initial step in the investigation of suspected venous thromboembolism. Chest 2003; 124: 1116-1119.