Materials and Methods

A retrospective case-control study was conducted at an academic hospital under institutional review board approval. Hospital records from Jan. 1, 2002, to Dec. 31, 2008, were searched to identify women between the ages of 18 and 45 years who were diagnosed with DVT using International Classification of Diseases , ninth revision (ICD-9) codes (451.1, 451.2, 453.41, 453.40). Cross-sectional imaging was necessary for venous stenosis measurements, and all patients without computed tomography (CT) or magnetic resonance (MR) imaging of the lower abdomen or pelvis were excluded.

The case subjects were defined as those with a first-time, acute presentation of a lower-extremity DVT that was visually confirmed by ultrasound, CT, or MR imaging. Exclusion criteria were then used to minimize misclassification of outcomes within these case subjects. Patients were excluded if no DVT was found on imaging or if they had a history of chronic venous disease or previous lower-extremity surgical or endovascular vascular procedures that may have distorted the iliac vein anatomy. Furthermore, because nearly all cases of IVCS occur on the left, only subjects with unilateral left-sided DVT were included.

The control subjects consisted of women between the ages of 18 and 45 years who presented to the emergency room from January 2002 to December 2008 with a chief complaint of abdominal pain (ICD-9 codes 789.01-789.09) and who were evaluated with CT imaging of the abdomen and pelvis. Subjects were excluded from the control population if they had a prior history of DVT or lower-extremity surgical or endovascular procedure.

The electronic medical record for all subjects was reviewed to assess whether combination oral contraceptives were used at the time of presentation. Patients using any form of progestin-only or nonhormonal contraceptives were considered as nonusers of COCs. Additional prothrombotic risks were also identified, including smoking, active malignancy, pregnancy, self-described inherited thrombophilia or that confirmed by hypercoagulability testing, and recent prolonged travel or immobilization. A patient with any of these risk factors was considered as having an additional hypercoagulable state in our statistical modeling.

CT scans were performed on either an 8 row or 16 row multidetectors (General Electric Medical Systems, Milwaukee, WI). MR imaging was performed on a 1.5-Tesla systems (General Electric Medical Systems) and included gradient-echo sequences and dynamic time-of-flight spoiled gradient-echo sequences. Axial CT and MR images of 5 mm thickness or less were reviewed, and the minor diameter of the LCIV measured at the point at which the right common iliac artery crosses anterior to the left iliac vein. The cross-sectional minor axis diameter of the right common iliac vein was measured 1 cm below the inferior vena cava bifurcation. Measurements were performed independently by 2 reviewers (K.T.C. and L.V.H.) who were blinded to the subject’s clinical presentation. The percent stenosis was calculated by dividing the LCIV minor diameter by the right common iliac vein minor diameter then subtracting this percentage from 100.

Simplified assumptions were made to determine the sample size needed in this case-control study. Based on the population frequencies of 17.3% women using COCs and 20% with iliac vein compression, we calculated approximately 3.5% of the population would concurrently have both conditions. We hypothesized that stenosis-induced stasis would have a prothrombotic effect independent from COC-related thrombophilia, and therefore, the relative risks of DVT for COC use and significant venous stenosis would be multiplicative. Compared with the patient with no risk factors, prior studies have estimated COC use and significant venous stenosis increased the relative risk of DVT by 3 and 7, respectively, resulting in a combined relative risk of both factors to be 21 times above baseline. With these assumptions, we calculated a sample size of 17 subjects was necessary to detect a significant effect (α = 0.05, β = 0.20). We then conservatively doubled this sample size to include the first 35 cases and controls that met our inclusion criteria.

Statistical analysis was performed using SAS version 9.1 (SAS Institute, Inc, Cary, NC). The likelihood of venous thromboembolism with the primary factors of COC use and venous stenosis was assessed using logistic regression models adjusted for age and a variable representing the presence of additional hypercoagulable states. The effect of venous compression on DVT was reported for each percent increase in stenosis. A subgroup analysis was also performed to compare the odds of DVT for patients with and without COC use and with and without a clinically significant amount of IVCS (defined as ≥70% stenosis, based the anatomical measurements from Oguzkurt et al and Tye et al ). The odds ratios and 95% confidence intervals were calculated, and statistical significance was set at an alpha level of 0.05.