An Evaluation of D-Dimer in the Diagnosis of Pulmonary Embolism

A Randomized Trial

6 June 2006 | Volume 144 Issue 11 | Pages 812-821

Background: It may be safe to omit additional diagnostic testing in selected patients with suspected pulmonary embolism (PE) who have a negative D-dimer test, but this approach has never been evaluated in a randomized, controlled trial.

Objective: To determine if additional diagnostic testing can be safely withheld in patients with suspected PE who have negative erythrocyte agglutination D-dimer test results.

Design: Randomized comparisons in 2 subgroups of a prospective multicenter study.

Setting: 7 university hospitals.

Patients: 1126 outpatients or inpatients with suspected PE; of these, 456 patients with negative erythrocyte agglutination D-dimer test results were randomly assigned to the intervention groups. Patients were classified into 2 clinical probability groups: those with a low clinical probability of PE (low-probability group) and those with a moderate or high clinical probability of PE, a nondiagnostic ventilation–perfusion lung scan, and no evidence of proximal deep venous thrombosis on bilateral ultrasonography (moderate- or high-probability group).

Interventions: The experimental intervention for both probability groups was no further diagnostic testing for PE. The control intervention for the low-probability group was a ventilation–perfusion lung scan followed by ultrasonography of the proximal deep veins of the legs on the same day. If the lung scan was nondiagnostic, ultrasonography of the legs was repeated 7 and 14 days later. The control intervention for the moderate- or high-probability group was ultrasonography of the proximal deep veins of the legs after 7 and 14 days. In the control and experimental groups, anticoagulation was withheld or withdrawn if PE was not diagnosed.

Measurements: Symptomatic venous thromboembolism (VTE) during 6 months of follow-up.

Results: Prevalence of VTE was 15.2% in the 1126 enrolled patients. In the low-probability group, VTE occurred during follow-up in 0 of 182 patients who had no additional diagnostic testing and in 1 of 185 patients who had additional testing (difference, –0.5 percentage point [95% CI, –3.0 to 1.6 percentage points]). In the moderate- or high-probability group, VTE occurred during follow-up in 1 of 41 patients who had no additional diagnostic testing and in 0 of 41 patients who had additional testing (difference, 2.4 percentage points [CI, –6.4 to 12.6 percentage points]).

Limitations: The authors could not enroll 2000 patients as originally planned; 3 randomly assigned patients did not receive the allocated intervention, and 7 received inadequate follow-up. Personnel who performed follow-up evaluations were not blinded to the results of diagnostic testing at enrollment or to allocation group assignments.

Conclusion: In patients with a low probability of PE who have negative D-dimer results, additional diagnostic testing can be withheld without increasing the frequency of VTE during follow-up. Low clinical probability and negative D-dimer results occur in 50% of outpatients and in 20% of inpatients with suspected PE.

*For other persons and institutions who participated in this study, see the Appendix.

Editors' Notes Context Is it safe to withhold additional testing in patients with suspected pulmonary embolism (PE) and negative D-dimer test results? Contribution This randomized trial evaluated the effect of further testing after negative D-dimer test results in patients with low pretest probability (group A) or moderate or high pretest probability (group B) of PE. At 6 months, 0 of 182 (group A) and 1 of 41 (group B) patients with no further testing had had symptomatic venous thromboembolism, compared with 1 of 185 (group A) and 0 of 41 (group B) patients with further testing. Cautions Few moderate- or high-probability patients were studied. Implications Additional diagnostic testing seems unnecessary in patients with low pretest probability of PE and negative D-dimer test results. —The Editors

 

Author and Article Information

From McMaster University and the Henderson Research Centre, Hamilton, Ontario, Canada; University of Ottawa, Ottawa, Ontario, Canada; Dalhousie University, Halifax, Nova Scotia, Canada; and University of Western Ontario, London, Ontario, Canada.

ClinicalTrials.gov identifier: NCT001825

Acknowledgments: Agen Biomedical Ltd., Brisbane, Australia, provided the D-dimer assays used in this research.

Grant Support: By the Canadian Institutes of Health Research (MT-14092). Drs. Kearon and Douketis were supported by the Heart and Stroke Foundation of Canada. Drs. Ginsberg, Weitz, and Crowther were supported by the Heart and Stroke Foundation of Ontario. Drs. Lee, Ginsberg, Weitz, and Wells were supported by the Canadian Institutes of Health Research. Dr. Bates was supported by the Canadian Institutes of Health Research University Industry Program (bioMerieux, Inc.). Dr. Kovacs was supported by the University of Western Ontario. Dr. Anderson was supported by Dalhousie University.

Potential Financial Conflicts of Interest: Consultancies: M.A. Crowther (Pfizer, Sanofi-Aventis, Leo Laboratories, AstraZeneca, Sandoz), J. Douketis (Agen Biomedical Ltd.); Honoraria: M.A. Crowther (Pfizer, Sanofi-Aventis, AstraZeneca, GlaxoSmithKline); Grants received: M.A. Crowther (Leo Laboratories, Sanofi-Aventis, Pfizer).

Corresponding Author: Clive Kearon, MB, PhD, Hamilton Health Sciences, Henderson Division, 711 Concession Street, Hamilton, Ontario L8V 1C3, Canada; e-mail, kearonc{at}mcmaster.ca.

Current Author Addresses: Drs. Kearon, Lee, Weitz, and Linkins: Henderson General Hospital, Hamilton Health Sciences Hospital, 711 Concession Street, Hamilton, Ontario L8V 1C3, Canada.

Drs. Ginsberg, Bates, and Brill-Edwards: McMaster University Medical Centre, Room 3W15, 1200 Main Street West, Hamilton, Ontario L8S 4L8, Canada.

Drs. Douketis and Crowther: St. Joseph's Hospital, Room L 208-4, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6, Canada.

Dr. Turpie: Hamilton General Hospital, Hamilton Health Sciences Hospital, 237 Barton Street East, Hamilton, Ontario L8L 2X2, Canada.

Dr. Wells: The Ottawa Hospital, Civic Parkdale Clinic, 467-737 Parkdale Avenue, Ottawa, Ontario K1Y 1J8, Canada.

Dr. Anderson: Queen Elizabeth II Health Sciences Centre, Room 430, Bethune Building, 1278 Tower Road, Halifax, Nova Scotia B3H 2Y9, Canada.

Dr. Kovacs: Victoria Hospital, 800 Commissioner's Road East, Room A2-401, London, Ontario N6A 4G5, Canada.

Mr. Julian, Ms. Bonilla, and Dr. Gent: Clinical Trials and Methodology Group, Henderson Research Centre, 711 Concession Street, Hamilton, Ontario L8V 1C3, Canada.

Author Contributions: Conception and design: C. Kearon, J.S. Ginsberg, M.J. Kovacs, P. Wells, D.R. Anderson.

Analysis and interpretation of the data: C. Kearon, J.S. Ginsberg, J.A. Julian, L.R. Bonilla, M. Gent.

Drafting of the article: C. Kearon, J.S. Ginsberg.

Critical revision of the article for important intellectual content: C. Kearon, J.S. Ginsberg, J. Douketis, A.G. Turpie, S.M. Bates, A.Y. Lee, M.A. Crowther, J.I. Weitz, P. Brill-Edwards, P. Wells, D.R. Anderson, M.J. Kovacs, L.-A. Linkins, J.A. Julian, L.R. Bonilla, M. Gent.

Final approval of the article: C. Kearon, J.S. Ginsberg, J. Douketis, A.G. Turpie, S.M. Bates, A.Y. Lee, M.A. Crowther, P. Brill-Edwards, P. Wells, D.R. Anderson, M.J. Kovacs, L.-A. Linkins, J.A. Julian, L.R. Bonilla, M. Gent.

Provision of study materials or patients: C. Kearon, J.S. Ginsberg, J. Douketis, A.G. Turpie, S.M. Bates, A.Y. Lee, M.A. Crowther, J.I. Weitz, P. Brill-Edwards, P. Wells, D.R. Anderson, M.J. Kovacs, L.-A. Linkins.

Statistical expertise: J.A. Julian.

Obtaining of funding: C. Kearon, J.S. Ginsberg, P. Wells, D.R. Anderson, M.J. Kovacs.

Administrative, technical, or logistic support: J.A. Julian, L.R. Bonilla, M. Gent.

Collection and assembly of data: C. Kearon, J.S. Ginsberg, J.A. Julian, L.R. Bonilla, M. Gent.

Read all Rapid Responses

D-dimer Should Be Viewed with Caution

Abdul-Karim Elhabyan, et al.

Annals Online, 15 Jun 2006 [Full text]

Won't it be the normal expectant result.?

Jeevan P Marasinghe

Annals Online, 19 Jun 2006 [Full text]