Bernardi E, Camporese G, Büller HR, et al. Serial 2-Point Ultrasonography Plus D-Dimer vs Whole-Leg Color-Coded Doppler Ultrasonography for Diagnosing Suspected Symptomatic Deep Vein Thrombosis: A Randomized Controlled Trial. JAMA. 2008;300(14):1653–1659. doi:10.1001/jama.300.14.1653
Objective: To assess if using serial 2-point ultrasonography and whole-leg ultrasonography are equivalent for the management of symptomatic outpatients with suspected deep vein thrombosis of the lower extremities.
Design: Prospective, randomized, multi-center study of symptomatic outpatients (N=2465) with a first episode of suspected lower extremities DVT who were randomized to undergo 2-point or whole-leg ultrasonography. Data collected from ultrasound laboratories of 14 Italian universities or civic hospitals between January 1, 2003 and December 21, 2006 with follow-up after 3 months resulting in study completion on March 20, 2007.
Inclusion Criteria: All consecutive outpatients who were referred by the emergency department or a primary care physician to 1 of the 14 study centers with a first episode of suspected symptomatic DVT of the lower extremities.
Exclusion Criteria: Pregnancy, age younger than 18 years, history of venous thromboembolism, suspected pulmonary embolism, life expectancy of less than 3 months, ongoing anticoagulation (>48 hours), mandatory indication for anticoagulation (eg, atrial fibrillation), and geographic inaccessibility to follow up.
Methods: Eligible patients were randomly assigned to either the 2-point or the whole-leg ultrasonography group. In the 2-point group, patients with normal ultrasound findings at presentation underwent D-dimer testing. If the D-dimer test was normal, these patients were spared further imaging and were not anticoagulated. If the D-dimer test was abnormal, these patients were scheduled for a repeat ultrasonography 1 week later, or earlier if clinically indicated. At the 1 week visit, if the repeat ultrasonography was normal, these patients were not anticoagulated and did not need further workup. In the whole-leg group, patients with normal ultrasonography findings at presentation were not anticoagulated and did not require further imaging. For both groups, patients with normal initial ultrasonography results at presentation were scheduled for a 3-month follow up visit which included a standardized interview, a physical exam, and an ultrasonographic evaluation. Telephone calls using a standardized questionnaire were used for patients who were unavailable for an in person visit.
All procedures were performed by certified physicians. In the 2-point strategy, a linear probe in the transverse plane is used to look at the common femoral vein at the groin and the popliteal vein in the popliteal fossa. If the vein is compressible, the test is normal; if the vein is incompressible, the test is abnormal. In this group, a D-dimer test was also utilized, which looks at red blood cells agglutination. No visible agglutination was categorized as a normal test result and visible agglutination or noninterpretable findings were categorized as abnormal. In the whole-leg strategy, a linear probe in transverse plane was used to look at all the veins in the lower extremities including the proximal femoral veins and the popliteal vein. In patients with normal proximal findings, the calf veins were then imaged, which included the axial and the muscular veins. Vein incompressibility was also the sole diagnostic criteria. Adjunctive criteria for abnormal testing of the muscular veins only included lack of spontaneous or reverse-flow intraluminal color-filling after augmentation maneuvers.
Primary Objective: To assess the incidence of objectively proven symptomatic VTE occurring during a 3-month follow-up period in patients with normal initial ultrasonographic findings at presentation using either 2-point ultrasonography strategy or whole-leg strategy.
Results: 2098 patients were randomized to either the 2-point strategy (N=1045) or whole-leg strategy (N=1053). In the 2-point group, 231 (22.1%; 95% CI, 19.6%-24.6%) had abnormal findings at initial diagnostic workup. A total of 217 patients had abnormal ultrasound findings and 828 had normal test results. 256 of the 828 (30.9%) that underwent subsequent D-dimer testing had abnormal results and were scheduled for a repeat ultrasound in 1 week. 14 of the 256 patients (5.5%) with abnormal D-dimer testing had abnormal repeat ultrasounds. Therefore, the remaining 814 patients were eligible for 3-month follow-up. In the whole-leg group, 278 (26.4%; 95% CI, 23.7%-29.1%) had abnormal ultrasound findings at presentation. The remaining 775 patients were not anticoagulated and were followed up for 3 months. At the 3-month follow-up, the incidence of confirmed symptomatic VTE in the 2-point group was 0.9% (95% CI, 0.3%-1.8%). In the whole-leg group, the incidence was 1.2% (95% CI, 0.5%-2.2%). The observed difference between the 2 groups was 0.3% (95% CI, -1.4% to 0.8%).
Discussion: This study shows that the 2-point and whole-leg strategies are equivalent in the management of symptomatic patients with suspected DVT. Despite a significantly higher initial prevalence of DVT in the whole-leg group (absolute difference, 4.3%; 95% CI, 0.5%-8.1%), the long-term outcomes of the patients were similar. The difference was entirely accounted for by cases of isolated calf DVT identified by the whole-leg strategy which suggests that detecting isolated calf DVT may not be as relevant as previously suspected. In addition, the initial prevalence of proximal DVT were similar in both groups (22.1% in the 2-point group vs 20.2% in the whole-leg group). This demonstrates that thorough evaluation including the superficial and deep femoral veins are not necessary as it did not increase the overall diagnostic yield of the whole-leg strategy.
Takeaway: Both serial 2-point ultrasonography plus D-dimer and whole-leg color-coded Doppler ultrasonography are reliable diagnostic tools for managing symptomatic patients with suspected DVT of the lower extremities. The 2-point method is simple, convenient and widely available, although it does require repeat testing in some patients. The whole-leg method offers a 1-day answer for patients with severe calf complaints, travelers and those living far away from healthcare services, but requires more experienced personnel so less readily available, possibly more expensive and may expose patients to the risks of unnecessary anticoagulation.
Author: Christine Chen, MS4