Abstract & Commentary
Source: Wells PS, et al. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. N Engl J Med 2003;349:1227-1235.
The authors of this randomized, controlled study sought to determine whether incorporation of a D-dimer testing strategy in patients with suspected deep-vein thrombosis (DVT) would reduce the need for ultrasound (US) imaging without compromising patient safety. Adult patients were recruited from thrombosis units and emergency departments (EDs), and were excluded if they were terminally ill, pregnant, taking warfarin, or if a pulmonary embolism (PE) was suspected.
The study design was complex and employed four different treatment algorithms. The clinical likelihood of DVT was first determined using previously validated criteria.1 Patients were randomized to a control group in which conventional US testing was performed, or to a D-dimer group in which US was performed selectively. Control group patients with low pre-test DVT likelihood underwent US imaging alone, while low-risk D-dimer group patients underwent US only if the D-dimer test was positive. Control group patients with high pre-test DVT likelihood underwent US, and those with negative studies had a repeat US at one week.
D-dimer group patients with high DVT likelihood all underwent US; those with negative US and negative D-dimers had no further testing done, while those with negative US and positive D-dimers had a repeat US study at one week. D-dimer testing was performed using either the SimpliRED assay (American Diagnostica Inc., Greenwich, CT) or the IL-Test (Instrumentation Laboratory, Lexington, MA). The study endpoint was a thromboembolic event (development of a proximal DVT or PE) within three months in a patient in whom DVT had been ruled out using the appropriate testing strategy.
The authors enrolled 1096 patients with an overall DVT prevalence of 16%. Among the 530 patients in the control group (US only), six (1.4) had a thromboembolic event within three months after initially having a DVT ruled out. Among the 566 patients in the D-dimer group, two (0.4%) had a thromboembolic event within three months after initially having a DVT excluded. This difference was not significant. Thirty-nine percent of the
patients in the D-dimer group required no US testing—that is, they were low-risk and had negative D-dimer results—and only two of these 218 non-imaged patients ultimately had a thromboembolic event. Furthermore, follow-up testing was necessary for only 18% of patients in the D-dimer group, while 35% of control patients required further study at one week. The authors conclude that DVT safely can be excluded in low-risk patients with negative D-dimer tests, and that no US is necessary in such patients.
Commentary by David J. Karras, MD
This study is powerful and may have a great impact on ED practice. However, great care is necessary to avoid misapplication of its findings. It is important to recognize that all patients determined to be at high risk for DVT underwent US study. Thus, familiarity with the Wells risk stratification model is essential.1 Second, the authors used only D-dimer tests known to have extremely high sensitivity for DVT—the SimpliRED assay (a qualitative whole-blood agglutination assay) and the IL-test (a quantitative latex agglutination assay). Multiple D-dimer tests exist, some with sensitivities as low as 80%, and there is no standardization of results between the assays.2 The testing strategies employed in this study cannot be extrapolated to sites using less sensitive D-dimer tests.3
Provided that emergency physicians carefully consider the test being utilized and select appropriate patients, the results of this study make it feasible for EDs to initiate D-dimer-based DVT evaluation policies in an effort to save time and cost and to eliminate the need for follow-up testing in up to one-third of patients. As an afterward, the three references listed below are outstanding clinical reviews of approach to the patient in whom a DVT or PE is suspected.
Dr. Karras, Associate Professor of Emergency Medicine, Department of Emergency Medicine Temple University School of Medicine, Director of Emergency Medicine Research, Temple University Hospital, Philadelphia, PA, is on the Editorial Board of Emergency Medicine Alert.
1. Wells PS, et al. Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet 1997;350:1795-1798.
2. Fedullo PF, et al. Evaluation of suspected pulmonary embolism. N Engl J Med 2003;349:1247-1256.
3. Bockenstedt P. D-dimer in venous thromboembolism. N Engl J Med 2003;349:1203-1204.