A Randomized Trial of Diagnostic Strategies after Normal Proximal Vein Ultrasonography for Suspected Deep Venous Thrombosis: D-Dimer Testing Compared with Repeated Ultrasonography

5 April 2005 | Volume 142 Issue 7 | Pages 490-496

Background: With suspected deep venous thrombosis and normal results on proximal vein ultrasonography, a negative D-dimer result may exclude thrombosis and a positive D-dimer result may be an indication for venography.

Objective: To evaluate and compare the safety of 2 diagnostic strategies for deep venous thrombosis.

Design: Randomized, multicenter trial.

Setting: Four university hospitals.

Patients: 810 outpatients with suspected deep venous thrombosis and negative results on proximal vein ultrasonography.

Interventions: Erythrocyte agglutination D-dimer testing followed by no further testing if the result was negative and venography if the result was positive (experimental) or ultrasonography repeated after 1 week in all patients (control).

Measurements: Symptomatic deep venous thrombosis diagnosed initially and symptomatic venous thromboembolism during 6 months of follow-up.

Results: Nineteen of 408 patients (4.7%) in the D-dimer group and 3 of 402 patients (0.7%) in the repeated ultrasonography group initially received a diagnosis of deep venous thrombosis (P < 0.001). During follow-up of patients without a diagnosis of deep venous thrombosis on initial testing, 8 patients (2.1% [95% CI, 0.9% to 4.0%]) in the D-dimer group and 5 patients (1.3% [CI, 0.4% to 2.9%]) in the repeated ultrasonography group developed symptomatic venous thromboembolism (difference, 0.8 percentage point [CI, –1.1 to 2.9 percentage points]; P > 0.2). Venous thromboembolism occurred in 1.0% (CI, 0.2% to 2.8%) of those with a negative D-dimer result.

Limitations: Seventy patients (8.6%) deviated from the diagnostic protocols, and 9 patients (1.1%) had inadequate follow-up.

Conclusion: In outpatients with suspected deep venous thrombosis who initially had normal results on ultrasonography of the proximal veins, a strategy based on D-dimer testing followed by no further testing if the result was negative and venography if the result was positive had acceptable safety and did not differ from the safety of a strategy based on withholding anticoagulant therapy and routinely repeating ultrasonography after 1 week.

Editors' Notes Context Physicians use several strategies to diagnose deep venous thrombosis (DVT). Contribution This trial randomly assigned 810 outpatients with suspected DVT and negative results on proximal vein ultrasonography to repeated ultrasonography at 1 week or D-dimer testing followed by no further tests if results were negative and venography if results were positive. Repeated ultrasonography diagnosed fewer DVTs than the D-dimer strategy (0.7% vs. 4.7%). In both groups followed for 6 months, only 1% to 2% of patients without DVT on initial testing developed symptomatic thromboembolism. Implications In patients with suspected DVT and negative results on proximal vein ultrasonography, a D-dimer–based strategy that minimizes additional assessments had similar safety to repeated ultrasonography. –The Editors

 

Author and Article Information

From McMaster University and the Henderson Research Centre, Hamilton, Ontario, Canada.

Grant Support: By the National Health Research Development Program of Health Canada (grant 6606-5620-400). AGEN Biomedical Ltd. donated the D-dimer kits. Drs. Kearon and Douketis are supported by the Heart and Stroke Foundation of Canada. Drs. Ginsberg is supported by the Heart and Stroke Foundation of Ontario. Drs. Crowther and Ginsberg are supported by the Canadian Institutes of Health Research. Dr. Bates is supported by the Canadian Institutes of Health Research, University–Industry Program. Dr. Lee is supported by the Canadian Institutes of Health Research, Drug Research and Development Program.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Clive Kearon, MB, PhD, Hamilton Health Sciences, Henderson Division, 711 Concession Street, Hamilton, Ontario, L8V 1C3.

Current Author Addresses: Drs. Kearon and Lee: 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 L87 3Z5, Canada.

Drs. Crowther and Douketis: 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.

Ms. Finch and Professor 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.

Analysis and interpretation of the data: C. Kearon, J.S. Ginsberg, 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, M.A. Crowther, A.G. Turpie, S.M. Bates, A. Lee, P. Brill-Edwards, T. Finch, M. Gent.

Final approval of the article: C. Kearon, J.S. Ginsberg, J. Douketis, M.A. Crowther, A.G. Turpie, S.M. Bates, A. Lee, P. Brill-Edwards, T. Finch, M. Gent.

Provision of study materials or patients: C. Kearon, J.S. Ginsberg, J. Douketis, M.A. Crowther, A.G. Turpie, S.M. Bates, A. Lee, P. Brill-Edwards.

Statistical expertise: C. Kearon, M. Gent.

Obtaining of funding: C. Kearon, J.S. Ginsberg.

Administrative, technical, or logistic support: T. Finch, M. Gent.

Collection and assembly of data: T. Finch.

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