How long to stay on anticoagulants: Study taps D-dimer test for answers

In a study reported in the October 26, 2006 issue of the New England Journal of Medicine, the D-dimer test was evaluated as a tool for determining if it was safe for an individual to stop anticoagulant therapy after an initial, 3-month course of treatment. The D-dimer test measures one of the products of the breakdown of clots (fibrin degradation products or FDPs) in the blood. A positive test indicates an abnormally high level of these in the body and points to a tendency to form blood clots inappropriately. The test is currently used to help rule out deep vein thrombosis (DVT), which involves clots that can block blood flow in the deep veins of the body, usually the legs, or pulmonary emboli (PE), which involves clots in the lungs. In some patients, an elevated D-dimer level may identify an increased likelihood to form a clot, referred to as a hypercoagulable state. Deciding how long certain patients with DVT should continue anticoagulant therapy to prevent another blood clot is an issue of concern for healthcare providers. The D-dimer test can be useful, concluded the “Prolong” study group.

Physicians want to know who should be protected from clotting with a prolonged course of therapy versus who is at low risk and should be spared the risks of bleeding related to the therapy. In the study, the D-dimer test was performed on patients one month after stopping anticoagulant therapy. Those patients with normal D-dimer results did not resume therapy and those with high levels of D-dimer were randomly divided into two groups: those that resumed therapy and those that did not but were monitored for recurrence of clots. The researchers found that subjects with an abnormally high level of D-dimer one month after stopping the initial course of therapy suffered a significant rate of recurrence. The study found that resuming therapy reduced the rate of recurrence.

Conducted in Italy, the Prolong study followed 608 adults for 18 months. The subjects were patients who had received the therapy (either warfarin or acenocoumarol) for three months after being diagnosed with “apparently unprovoked, symptomatic venous thromboembolism.” That is, each patient had had a blood clot in his or her leg or another large vein in the body or a pulmonary embolism (a deep vein clot that broke apart and traveled to an artery in the lungs). The study included only patients whose condition was “unprovoked” (not triggered by an event such as surgery or a known major medical trauma). Persons with unprovoked DVT are more likely to suffer another clot or a pulmonary embolism.

Articles commenting on the study noted both the approach’s strengths and the study’s limitations. “Identifying patients whose risk for recurrence is low, and whose anticoagulation therapy could be safely discontinued, is a priority,” wrote David Green, in Journal Watch Oncology and Hematology. The commentary pointed out that using D-dimer tests to evaluate low-risk patients helps adjust anticoagulation duration on a case-by-case basis, and Green outlined a strategy for low-risk patients based on the study’s findings. However, safety and efficacy require further evaluation, and Harlan Krumholz noted in Journal Watch Cardiology that “the data do not show whether a strategy of continuous anticoagulation therapy for everyone in the trial would have been better than a strategy of using D-dimer testing to guide decisions about anticoagulation. Without that evidence, D-dimer testing after 3 months…remains a strategy of uncertain value.” The authors of the study agree that further research is needed to clearly establish the optimal course of anticoagulation therapy.

Sources
S1
D-dimer to establish duration of anticoagulation after venous thromboembolism. On the Internet: http://ClinicalTrails.gov/show/NCT00264277. Accessed 27 Nov 2006.

S2
Green, D. Duration of oral anticoagulants for venous thromboembolism. 30 Oct 2006. Journal Watch Oncology and Hematology. On the Internet: http://oncology-hematology.jwatch/org/cgi/content/full/2006/1030/1. Accessed 27 Nov 2006.

S3
Krumholz, H. M. Should D-dimer testing guide the duration of anticoagulation after unprovoked VTE? 25 Oct 2006. Journal Watch Cardiology. On the Internet: http://cardiology/jwatch/org/cgi/content/full/2006/1025/4. Accessed 27 Nov 2006.

S4
Palareti G, Cosmi B, Legnani C, et al. D-dimer testing to determine the duration of anticoagulation therapy. 26 Oct 2006. N Engl J Med. 355(17):1780-9. Abstract accessed on the Internet: http://content.nejm.org/cgi/content/abstract/355/17/1780. Accessed 27 Nov 2006.

Tests: D-dimer