CLINICAL STUDIES Does the Location of Thrombosis Determine the Risk of Disease Recurrence in Patients with Proximal Deep Vein Thrombosis?* James D. Douketis, MD, Mark A. Crowther, MD, MSc, Gary A. Foster PhD, Jeffrey S. Ginsberg MD PURPOSE: To determine if the location of deep vein throm- bosis is a predictor of recurrent venous thromboembolism dur- ing the initial 3 months of anticoagulant therapy. METHODS: The study population consisted of 1,149 consec- utive patients with symptomatic proximal deep vein thrombo- sis. In all patients, deep vein thrombosis was confirmed by Du- plex ultrasound or venography and was classified as popliteal, femoral, or iliofemoral. Patients received initial treatment with unfractionated heparin, enoxaparin, or reviparin for least 4 days, as well as a coumarin derivative, with a target international normalized ratio of 2.0 to 3.0, starting on the 1st or 2nd day of treatment. All patients were followed for 3 months, and all ep- isodes of recurrent venous thromboembolism were confirmed with objective diagnostic tests. RESULTS: The overall rate of recurrent venous thromboem- bolism during the initial 3 months of anticoagulant therapy was 5.5% (63/1,149). The rate of recurrence in patients with popli- teal vein thrombosis was 5.1% (23/453); in patients with femo- ral vein thrombosis, it was 5.3% (34/645); and in patients with iliofemoral vein thrombosis, it was 11.8% (6/51). Two clinical risk factors were associated with an increased risk of recurrent venous thromboembolism: iliofemoral vein thrombosis (odds ratio [OR] = 2.4; 95% confidence interval [CI]: 0.95, 5.9), and cancer (OR = 2.6; 95% CI: 1.5, 4.4). CONCLUSIONS: Patients with extensive iliofemoral vein thrombosis who receive conventional anticoagulant therapy have a greater than twofold higher risk of developing recurrent venous thromboembolism than patients without iliac vein in- volvement (i.e., 11.8% vs. 5.2%). Prospective studies are needed to determine whether alternative antithrombotic strategies are warranted in such patients. Am J Med. 2001;110:515–519. 2001 by Excerpta Medica, Inc. T raditionally, patients with lower limb deep vein thrombosis have been separated into two prog- nostic categories: those with proximal thrombosis and those with distal (calf) thrombosis. Proximal vein thrombosis, which is defined as thrombosis that involves the popliteal or more proximal veins, is associated with a threefold higher risk of recurrent venous thromboembo- lism than distal vein thrombosis (1). Because deep vein thrombosis usually involves the veins in a continuous manner, however, the prognosis of patients with deep vein thrombosis may depend not only on whether there is proximal or distal vein involvement, but also on the ex- tent of proximal thrombosis. Thus, patients with popli- teal vein thrombosis, in whom the thrombus extends only 2 to 4 cm beyond the distal veins, might be expected to have a good prognosis, whereas patients with femoral or iliofemoral vein thrombosis, in whom the thrombus extends from the knee to the inguinal ligament or be- yond, might have a worse prognosis. Although a cohort study of 355 patients with deep vein thrombosis found no difference in the rates of recurrent thromboembolism ac- cording to the location of thrombosis (2), there may have been too few patients to detect differences in recurrence rates between patient subgroups with proximal vein thrombosis. Furthermore, patients in this study received an extended duration of heparin therapy of at least 10 days, which may have influenced the clinical course of different patient subgroups with proximal vein thrombo- sis. In other cohort studies of patients with deep vein thrombosis, the location of thrombosis was not investi- gated as a possible risk factor for recurrence (3–7), al- though one study found that unspecified proximal vein thrombosis was associated with a greater than twofold higher risk of recurrence than distal vein thrombosis (3). To determine if the location of deep vein thrombosis is * Access the “Journal Club” discussion of this paper at http://www. elsevier.com/locate/ajmselect/ Accepted for publication January 19, 2001. From the Department of Medicine, McMaster University (JDD, MAC, JSG) St. Joseph’s Hospital (JDD, MAC, GAF), and the Father Sean O’Sullivan Research Centre (GAF), Hamilton, Ontario,Canada. Dr. Douketis is the recipient of a research scholarship from the Heart and Stroke Foundation of Ontario, Dr. Crowther is the recipient of a research scholarship from the Canadian Institutes of Health Research, and Dr. Ginsberg is the recipient of a Career Investigator Award from the Heart and Stroke Foundation of Ontario. Requests for reprints should be addressed to Dr. James D. Douketis, St. Joseph’s Hospital, Room F-538, 50 Charlton Avenue East, Hamilton, Ontario, Canada, L8N 4A6; tel: (905) 521-6178; fax: (905) 521-6068 e-mail: jdouket@fhs.mcmaster.ca 2001 by Excerpta Medica, Inc. 0002-9343/01/$–see front matter 515 All rights reserved. PII S0002-9343(01)0066-1