d-Dimer for the Exclusion of Acute Venous Thrombosis and Pulmonary Embolism

A Systematic Review

  1. Paul D. Stein, MD;
  2. Russell D. Hull, MBBS, MSc;
  3. Kalpesh C. Patel, MBBS;
  4. Ronald E. Olson, PhD;
  5. William A. Ghali, MD, MPH;
  6. Rollin Brant, PhD;
  7. Rita K. Biel, BSc;
  8. Vinay Bharadia, MSc; and
  9. Neeraj K. Kalra, MD
  1. From Saint Joseph Mercy-Oakland, Pontiac, Michigan; Wayne State University, Detroit, Michigan; University of Calgary, Calgary, Alberta, Canada; and Oakland University, Rochester, Michigan.

    Abstract

    Background: Despite extensive literature, the diagnostic role of d-dimer for deep venous thrombosis (DVT) or pulmonary embolism (PE) remains unclear, reflecting multiple d-dimer assays and concerns about differing sensitivities and variability.

    Purpose: To systematically review trials that assessed sensitivity, specificity, likelihood ratios, and variability among d-dimer assays.

    Data Sources: Studies in all languages were identified by searching PubMed from 1983 to January 2003 and EMBASE from 1988 to January 2003.

    Study Selection: The researchers selected prospective studies that compared d-dimer with a reference standard. Studies of high methodologic quality were included in the primary analyses; sensitivity analysis included additional weaker studies.

    Data Extraction: Two authors collected data on study-level factors: d-dimer assay used, cutoff value, and whether patients had suspected DVT or PE.

    Data Synthesis: For DVT, the enzyme-linked immunosorbent assay (ELISA) and quantitative rapid ELISA dominate the rank order for these values: sensitivity, 0.96 (95% confidence limit [CL], 0.91 to 1.00), and negative likelihood ratio, 0.12 (CL, 0.04 to 0.33); and sensitivity, 0.96 (CL, 0.90 to 1.00), and negative likelihood ratio, 0.09 (CL, 0.02 to 0.41), respectively. For PE, the ELISA and quantitative rapid ELISA also dominate the rank order for these values: sensitivity, 0.95 (CL, 0.85 to 1.00), and negative likelihood ratio, 0.13 (CL, 0.03 to 0.58); and sensitivity, 0.95 (CL, 0.83 to 1.00), and negative likelihood ratio, 0.13 (CL, 0.02 to 0.84), respectively. The ELISA and quantitative rapid ELISA have negative likelihood ratios that yield a high certainty for excluding DVT or PE. The positive likelihood values, which are in the general range of 1.5 to 2.5, do not greatly increase the certainty of diagnosis. Sensitivity analyses do not affect these findings.

    Limitations: Although many studies evaluated multiple d-dimer assays, findings are based largely on indirect comparisons of test performance characteristics across studies.

    Conclusion: The ELISAs in general dominate the comparative ranking among the d-dimer assays for sensitivity and negative likelihood ratio. For excluding PE or DVT, a negative result on quantitative rapid ELISA is as diagnostically useful as a normal lung scan or negative duplex ultrasonography finding.

    Article and Author Information

    • Acknowledgments: The authors thank Natasha Burke, BSc, Adrian Jorgenson, BSc, and Jeanne Sheldon, BA, University of Calgary, for their assistance in preparing the manuscript and Trupti Patel, BS, for her help in analyzing the data.

    • Potential Financial Conflicts of Interest: None disclosed.

    • Requests for Single Reprints: Paul D. Stein, MD, Saint Joseph Mercy-Oakland, 44555 Woodward Avenue, Suite 107, Pontiac, MI 48341; e-mail, steinp{at}trinity-health.org.

    • Current Author Addresses: Dr. Stein: Saint Joseph Mercy-Oakland, 44555 Woodward Avenue, Suite 107, Pontiac, MI 48341.

    • Dr. Hull and Ms. Biel: Thrombosis Research Unit, University of Calgary, 601 South Tower, Foothills Hospital, 1403 29 Street Northwest, Calgary, Alberta T2N 2T9, Canada.

    • Dr. Patel: 712 Indian Creek Drive, Wilkes Park, PA 18702.

    • Dr. Olson: Office of the Vice Provost for Research and Graduate Studies, Oakland University, 520 O'Dowd Hall, Rochester, MI 48309-4401.

    • Dr. Ghali: University of Calgary, 3330 Hospital Drive Northwest, Calgary, Alberta T2N 4N1, Canada.

    • Dr. Brant: University of Calgary, 3310 Hospital Drive Northwest, Calgary, Alberta T2N 1N4, Canada.

    • Mr. Bharadia: University of Victoria, Cornett Building A238, 3800 Finnerty Road (Ring Road), Victoria, British Columbia V8P 5C2, Canada.

    • Dr. Kalra: Detroit Medical Center, Wayne State University, 4201 St. Antoine Street, Detroit, MI 48201.

    • Author Contributions: Conception and design: P.D. Stein, R.D. Hull, V. Bharadia.

    • Analysis and interpretation of the data: P.D. Stein, R.D. Hull, R.E. Olson, W.A. Ghali, R. Brant, R.K. Biel, V. Bharadia, N.K. Kalra.

    • Drafting of the article: P.D. Stein, R.D. Hull, R.E. Olson, R. Brant, R.K. Biel, V. Bharadia.

    • Critical revision of the article for important intellectual content: P.D. Stein, R.D. Hull, R.E. Olson, W.A. Ghali, R. Brant, V. Bharadia.

    • Final approval of the article: P.D. Stein, R.D. Hull, W.A. Ghali.

    • Provision of study materials or patients: P.D. Stein, R.D. Hull, V. Bharadia.

    • Statistical expertise: P.D. Stein, R.D. Hull, R.E. Olson, W.A. Ghali, R. Brant.

    • Obtaining of funding: P.D. Stein, R.D. Hull.

    • Administrative, technical, or logistic support: P.D. Stein, R.D. Hull, R.K. Biel, V. Bharadia.

    • Collection and assembly of the data: P.D. Stein, R.D. Hull, K.C. Patel, R.K. Biel, V. Bharadia, N.K. Kalra.

    Responses to this article

    • Comment on Stein article
      • Stephen J. Wolf
      Ann Intern Med published online October 26, 2009
    • Pitfalls of using D-dimer for exclusion of venous thromboembolism
      • John T. Philbrick and
      • Steven Heim and Joel M. Schectman
      Ann Intern Med published online October 26, 2009
    • D-dimer test in patients with cancer
      • Fabio Puglisi and
      • Edda Federico
      Ann Intern Med published online October 26, 2009

    Summaries for Patients

    • Summaries for Patients:Ability of Different d-Dimer Tests To Exclude Deep Venous Thrombosis and Pulmonary Embolism Ann Intern Med April 20, 2004 140:I-42
    • Letter:Appropriateness of Excluding Pulmonary Embolism
      • Herman M.A. Hofstee
      Ann Intern Med July 18, 2006 145:152
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