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Diagnostic accuracy of conventional or age adjusted D-dimer cut-off values in older patients with suspected venous thromboembolism: systematic review and meta-analysis

BMJ 2013; 346 doi: (Published 03 May 2013) Cite this as: BMJ 2013;346:f2492
  1. Henrike J Schouten, resident in geriatrics12,
  2. G J Geersing, general practitioner1,
  3. H L Koek, geriatrician2,
  4. Nicolaas P A Zuithoff, consultant in applied statistics1,
  5. Kristel J M Janssen, clinical epidemiologist3,
  6. Renée A Douma, resident internal medicine4,
  7. Johannes J M van Delden, professor of medical ethics1,
  8. Karel G M Moons, professor of clinical epidemiology1,
  9. Johannes B Reitsma, associate professor of clinical epidemiology1
  1. 1Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, PO Box 85500, 3508GA Utrecht, Netherlands
  2. 2Department of Geriatrics, University Medical Center Utrecht, Utrecht, Netherlands
  3. 3Mapi Consultancy, Houten, Netherlands
  4. 4Department of Vascular Medicine, Academic Medical Centre, Amsterdam, Netherlands
  1. Correspondence to: H J Schouten h.j.schouten-3{at}
  • Accepted 25 March 2013


Objective To review the diagnostic accuracy of D-dimer testing in older patients (>50 years) with suspected venous thromboembolism, using conventional or age adjusted D-dimer cut-off values.

Design Systematic review and bivariate random effects meta-analysis.

Data sources We searched Medline and Embase for studies published before 21 June 2012 and we contacted the authors of primary studies.

Study selection Primary studies that enrolled older patients with suspected venous thromboembolism in whom D-dimer testing, using both conventional (500 µg/L) and age adjusted (age×10 µg/L) cut-off values, and reference testing were performed. For patients with a non-high clinical probability, 2×2 tables were reconstructed and stratified by age category and applied D-dimer cut-off level.

Results 13 cohorts including 12 497 patients with a non-high clinical probability were included in the meta-analysis. The specificity of the conventional cut-off value decreased with increasing age, from 57.6% (95% confidence interval 51.4% to 63.6%) in patients aged 51-60 years to 39.4% (33.5% to 45.6%) in those aged 61-70, 24.5% (20.0% to 29.7% in those aged 71-80, and 14.7% (11.3% to 18.6%) in those aged >80. Age adjusted cut-off values revealed higher specificities over all age categories: 62.3% (56.2% to 68.0%), 49.5% (43.2% to 55.8%), 44.2% (38.0% to 50.5%), and 35.2% (29.4% to 41.5%), respectively. Sensitivities of the age adjusted cut-off remained above 97% in all age categories.

Conclusions The application of age adjusted cut-off values for D-dimer tests substantially increases specificity without modifying sensitivity, thereby improving the clinical utility of D-dimer testing in patients aged 50 or more with a non-high clinical probability.


  • We thank Nienke A F Verheijden for double checking our search and data extraction; Bianca Kramer for her help in the design of the search syntax; and Andrea Penaloza, Josien van Es, Gregoire Le Gal, Roger Schutgens, Cristina Legnani, Shanon Bates, Menno Huisman, and Melanie Tan for providing additional data.

  • Contributors: HJS, GJG, and JBR participated in the study concept and design, interpretation of data, and drafting of the manuscript. HJS, GJG, and NV performed the search and data extraction. RAD acquired additional data and critically revised the manuscript. HLK, KJMJ, and NPAZ critically revised the manuscript. JBR and NPAZ participated in analysis of the data. JBR, KGMM, and JJMD provided critical revision of the manuscript and study supervision. All authors had full access to all data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors participated in the revision and final approval of the manuscript.

  • Funding: This study was supported by the Netherlands Organization for Scientific Research (ZonMw project No 9120-8004, 918-10-615, and 17088-2502). The funder had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at (available on request from the corresponding author) and declare: all authors had financial support from the Netherlands Organization for Scientific Research (ZonMw project No 17088-2502, 917-46-360, and 945-04-009) for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: Not required.

  • Data sharing: No additional data available.

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