D-dimer can identify high-risk group for extended anticoagulation (PROLONG)

Clinical Question

Can the d-dimer level be used to guide decisions regarding the duration of anticoagulation for venous thromboembolism?

Bottom Line

The duration of anticoagulation involves an informed decision, made by the patient and the physician, that balances harm, benefit, cost, and convenience. This study provides additional information to help guide that decision. After the recommended 6 months to 12 months of anticoagulation, patients with an abnormal d-dimer result should consider extended and perhaps indefinite anticoagulation, while those with a normal d-dimer level should consider discontinuing anticoagulation. (LOE = 1b)


Legnani C, Tosetto A, Brusi C, et al, for the PROLONG Investigators. D-dimer testing to determine the duration of anticoagulation therapy. N Engl J Med 2006;355:1780-1789.  [PMID:17065639]

Study Design

Randomized controlled trial (single-blinded)






Outpatient (any)


Although the risk of recurrent venous thromboembolism (VTE) gradually declines with time from the index event, the risk of bleeding complications remains relatively constant. Thus, while extended anticoagulation reduces the risk of recurrent VTE, it also exposes patients to a greater risk of bleeding problems. In this study, patients with an initial episode of idiopathic VTE (eg, not pregnant, no recent immobilization or surgery, no cancer, and no antithrombin deficiency or antiphospholipid antibody syndrome) who had completed at least 3 months of oral anticoagulation were identified. The most recent guidelines from the American College of Chest Physicians recommend at least 6 months to 12 months of anticoagulation for these patients. Approximately half the study patients had between 7 months and 12 months of anticoagulation therapy, approximately one third had more than 12 months, and the rest had less than 6 months. The patients were told to stop taking their anticoagulants, and their d-dimer level was checked approximately 30 days later (the test is not accurate while taking vitamin K antagonists like warfarin). Patients who had a normal d-dimer test result (n=385) discontinued anticoagulation. If the test result was abnormal, the patient was randomly assigned to either continue anticoagulation with a target international normalized ratio of 2.5 or discontinue anticoagulation. All patients were followed up for up to 18 months and were evaluated every 3 months to 6 months. Any patient with signs or symptoms that possibly indicated VTE was evaluated using standard protocols for deep vein thrombosis (DVT) and/or pulmonary embolism (PE), and final outcomes were adjudicated by a committee blinded to treatment assignment. The primary outcome was the number of adverse events, which included recurrent DVT, PE, or a major bleeding episode. In the intention-to-treat analysis, patients with a normal d-dimer result experienced 4.4 adverse events per 100 person-years. Those with an abnormal result who discontinued anticoagulation had 10.9 adverse events per 100 person-years, while those who continued anticoagulation had only 2.0 adverse events per 100 person-years. The differences between the group of patients with the abnormal d-dimer results who were not anticoagulated and the other 2 groups were statistically significant, while the difference between patients with normal test results and those with abnormal results who continued anticoagulation was not. There was only 1 major bleeding episode, which occurred in a patient who had an abnormal result and continued anticoagulation.There were 3 deaths, 1 in each of the 3 groups.