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Systematic Review: d-Dimer to Predict Recurrent Disease after Stopping Anticoagulant Therapy for Unprovoked Venous Thromboembolism

Madeleine Verhovsek, MD; James D. Douketis, MD; Qilong Yi, PhD; Sanjay Shrivastava, MBBS, MPH; R. Campbell Tait, MBChB; Trevor Baglin, PhD; Daniela Poli, MD; and Wendy Lim, MD, MSc
[+] Article, Author, and Disclosure Information

From McMaster University and St. Joseph's Hospital, Hamilton, Ontario, Canada; Community Medicine, University of Ottawa, Ontario, Canada; Harvard Vanguard Medical Associates, Brigham and Women's Hospital, Boston, Massachusetts; Royal Infirmary, Glasgow, United Kingdom; Addenbrooke's Hospital, Cambridge, United Kingdom; and Centro di Riferimento Regionale per la Trombosi, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy.

Acknowledgment: The authors thank Drs. Sabine Eichinger (Vienna, Austria) and Gualtiero Palareti (Bologna, Italy) for providing information and data about their studies and Drs. John Eikelboom, Shannon Bates, and Clive Kearon (McMaster University, Hamilton, Ontario, Canada) for review of an earlier version of the manuscript. None of the persons listed received financial compensation for their contributions.

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: James D. Douketis, MD, St. Joseph's Hospital, Room F-544, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6, Canada; e-mail, jdouket@mcmaster.ca.

Current Author Addresses: Dr. Verhovsek: McMaster University, 1200 Main Street West, Hamilton, Ontario, L8N 3Z5, Canada.

Dr. Douketis: St. Joseph's Healthcare, Room F-544, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6, Canada.

Dr. Yi: Canadian Blood Services, 1800 Alta Vista Drive, Ottawa, Ontario K1G 4J5, Canada.

Dr. Shrivastava: Harvard Vanguard Medical Associates, 133 Brookline Avenue, Boston, MA 02215.

Dr. Tait: Royal Infirmary, Castle Street, Glasgow G4 0SF, United Kingdom.

Dr. Baglin: Addenbrooke's Hospital, Hills Road, Cambridge CB20QQ, United Kingdom.

Dr. Poli: Centro di Riferimento Regionale per la Trombosi, Azienda Ospedaliero-Universitaria Careggi, Florence 50034, Italy.

Dr. Lim: McMaster University, 50 Charlton Avenue East, Hamilton, Ontario L8N 4A6, Canada.

Ann Intern Med. 2008;149(7):481-490. doi:10.7326/0003-4819-149-7-200810070-00008
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Background: The optimal duration of anticoagulation for a first episode of unprovoked venous thromboembolism (VTE) is uncertain. Methods for predicting risk for recurrence may identify low-risk patients who are less likely to benefit from prolonged anticoagulation.

Purpose: To synthesize evidence evaluating the value of d-dimer as a predictor of recurrent disease in patients who have stopped anticoagulant therapy after a first unprovoked VTE.

Data Sources: The MEDLINE, EMBASE, CINAHL, and Cochrane databases were searched until March 2008 without language restrictions. The strategy was supplemented with manual review of reference lists and contact with content experts.

Study Selection: Randomized, controlled trials or prospective cohort studies that measured d-dimer after anticoagulant therapy in patients who received at least 3 months of anticoagulant treatment of unprovoked VTE.

Data Extraction: Two authors independently reviewed articles and extracted data.

Data Synthesis: Seven studies, totaling 1888 patients with a first unprovoked VTE, were eligible for analysis. During 4500 person-years of follow up, annual rates of recurrent VTE differed statistically significantly: 8.9% (95% CI, 5.8% to 11.9%) in patients with positive d-dimer results and 3.5% (CI, 2.7% to 4.3%) in patients with negative d-dimer results.

Limitation: The duration of anticoagulation, timing of d-dimer testing, and d-dimer assay varied across studies.

Conclusion: In patients who have completed at least 3 months of anticoagulation for a first episode of unprovoked VTE and after approximately 2 years of follow-up, a negative d-dimer result was associated with a 3.5% annual risk for recurrent disease, whereas a positive d-dimer result was associated with an 8.9% annual risk for recurrence. These rates should inform decisions about the balance of risks and benefits of prolonging anticoagulation.


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Study flow diagram.

VTE = venous thromboembolism.

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Appendix Figure 1.
Funnel plot for negative posttreatment d-dimer result: annual risk.
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Appendix Figure 2.
Funnel plot for positive posttreatment d-dimer result: annual risk.
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