D-dimer testing to determine the duration of anticoagulation therapy

N Engl J Med. 2006 Oct 26;355(17):1780-9. doi: 10.1056/NEJMoa054444.


Background: The optimal duration of oral anticoagulation in patients with idiopathic venous thromboembolism is uncertain. Testing of D-dimer levels may play a role in the assessment of the need for prolonged anticoagulation.

Methods: We performed D-dimer testing 1 month after the discontinuation of anticoagulation in patients with a first unprovoked proximal deep-vein thrombosis or pulmonary embolism who had received a vitamin K antagonist for at least 3 months. Patients with a normal D-dimer level did not resume anticoagulation, whereas those with an abnormal D-dimer level were randomly assigned either to resume or to discontinue treatment. The study outcome was the composite of recurrent venous thromboembolism and major bleeding during an average follow-up of 1.4 years.

Results: The D-dimer assay was abnormal in 223 of 608 patients (36.7%). A total of 18 events occurred among the 120 patients who stopped anticoagulation (15.0%), as compared with 3 events among the 103 patients who resumed anticoagulation (2.9%), for an adjusted hazard ratio of 4.26 (95% confidence interval [CI], 1.23 to 14.6; P=0.02). Thromboembolism recurred in 24 of 385 patients with a normal D-dimer level (6.2%). Among patients who stopped anticoagulation, the adjusted hazard ratio for recurrent thromboembolism among those with an abnormal D-dimer level, as compared with those with a normal D-dimer level, was 2.27 (95% CI, 1.15 to 4.46; P=0.02).

Conclusions: Patients with an abnormal D-dimer level 1 month after the discontinuation of anticoagulation have a significant incidence of recurrent venous thromboembolism, which is reduced by the resumption of anticoagulation. The optimal course of anticoagulation in patients with a normal D-dimer level has not been clearly established. (ClinicalTrials.gov number, NCT00264277 [ClinicalTrials.gov].).

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acenocoumarol / administration & dosage
  • Adult
  • Aged
  • Aged, 80 and over
  • Anticoagulants / administration & dosage*
  • Antiphospholipid Syndrome / diagnosis
  • Antithrombins / deficiency
  • Drug Administration Schedule
  • Fibrin Fibrinogen Degradation Products / analysis*
  • Follow-Up Studies
  • Hemorrhage / chemically induced
  • Humans
  • Middle Aged
  • Proportional Hazards Models
  • Prospective Studies
  • Pulmonary Embolism / blood
  • Pulmonary Embolism / diagnosis
  • Pulmonary Embolism / drug therapy*
  • Recurrence
  • Survival Analysis
  • Ultrasonography
  • Venous Thrombosis / blood
  • Venous Thrombosis / diagnostic imaging
  • Venous Thrombosis / drug therapy*
  • Vitamin K / antagonists & inhibitors
  • Warfarin / administration & dosage


  • Anticoagulants
  • Antithrombins
  • Fibrin Fibrinogen Degradation Products
  • fibrin fragment D
  • Vitamin K
  • Warfarin
  • Acenocoumarol

Associated data

  • ClinicalTrials.gov/NCT00264277