D-dimer testing to select patients with a first unprovoked venous thromboembolism who can stop anticoagulant therapy: a cohort study

Ann Intern Med. 2015 Jan 6;162(1):27-34. doi: 10.7326/M14-1275.


Background: Normal D-dimer levels after withdrawal of anticoagulant therapy are associated with a reduced risk for recurrence in patients with unprovoked venous thromboembolism (VTE) and may justify stopping treatment.

Objective: To determine whether patients with a first unprovoked VTE and negative D-dimer test result who stop anticoagulant therapy have a low risk for recurrence.

Design: Prospective management study with blinded outcome assessment. (ClinicalTrials.gov: NCT00720915).

Setting: 13 university-affiliated clinical centers.

Patients: 410 adults aged 75 years or younger with a first unprovoked proximal deep venous thrombosis or pulmonary embolism who had completed 3 to 7 months of anticoagulant therapy.

Intervention: Anticoagulant therapy was stopped if D-dimer test results were negative and was not restarted if results were still negative after 1 month.

Measurements: Recurrent VTE during an average follow-up of 2.2 years.

Results: In 319 patients (78%) who had 2 negative D-dimer results and did not restart anticoagulant therapy, rates of recurrent VTE were 6.7% (95% CI, 4.8% to 9.0%) per patient-year overall (42 of 319), 9.7% (CI, 6.7% to 13.7%) per patient-year in men (33 of 180), 5.4% (CI, 2.5% to 10.2%) per patient-year in women with VTE not associated with estrogen therapy (9 of 81), and 0.0% (CI, 0.0% to 3.0%) per patient-year in women with VTE associated with estrogen therapy (0 of 58) (P = 0.001 for the 3-group comparison).

Limitations: Imprecision in female subgroups. Results may not be generalizable to different D-dimer assays from the one used in the study.

Conclusion: The risk for recurrence in patients with a first unprovoked VTE who have negative D-dimer results is not low enough to justify stopping anticoagulant therapy in men but may be low enough to justify stopping therapy in women.

Primary funding source: Canadian Institutes of Health Research.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anticoagulants / adverse effects
  • Anticoagulants / therapeutic use*
  • Cause of Death
  • Female
  • Fibrin Fibrinogen Degradation Products / metabolism*
  • Hemorrhage / chemically induced
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Male
  • Middle Aged
  • Neoplasms / diagnosis
  • Platelet Aggregation Inhibitors / therapeutic use
  • Prospective Studies
  • Pulmonary Embolism / blood*
  • Pulmonary Embolism / drug therapy*
  • Recurrence
  • Risk Factors
  • Sex Factors
  • Stockings, Compression
  • Venous Thromboembolism / blood*
  • Venous Thromboembolism / drug therapy*
  • Withholding Treatment


  • Anticoagulants
  • Fibrin Fibrinogen Degradation Products
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Platelet Aggregation Inhibitors
  • fibrin fragment D

Associated data

  • ClinicalTrials.gov/NCT00720915