While it has been recognized that patients who develop superficial vein thrombosis (SVT) may be at considerable risk for developing concomitant deep vein thrombosis (DVT) or pulmonary embolism (PE) at the time of SVT diagnosis, data supporting this association are lacking or are widely variable, according to the authors of a review published in the Journal of Thrombosis and Haemostasis.
The results of the literature review, conducted by Matteo N. D. Di Minno, MD, from the Department of Advanced Biomedical Sciences at Federico Il University in Naples, Italy, and authors, confirms the relationship between SVT and DVT/PE and the benefit of screening for VTE in certain SVT patients.
“SVT has long been considered a benign entity, with more local than systemic implications,” Dr. Di Minno and authors wrote, “[and] SVT may be a manifestation of a systemic tendency to thrombosis.”
In this systematic literature review and meta-analysis, Dr. Di Minno and authors selected 22 studies (comprising a total of 4,379 patients with lower-limb SVT and concomitant DVT/PE).
Case reports, reviews, and animal studies were excluded from the analysis.
Results from the included studies were stratified based on the study design (prospective [n=15] vs. retrospective [n=7]). Twenty-one studies reported on the prevalence of DVT (n=4,358) and 11 (n=2,484) reported on the prevalence of PE.
The number of patients included in each study ranged from five to 844, the mean age ranged from 47 to 79 years, and the percent of female patients ranged from 47.6 percent to 80 percent. An active malignancy was reported in zero to 18.3 percent of patients, obesity in 16.2 to 35.8 percent, recent surgery in 3.7 to 30 percent, trauma in zero to 13.4 percent, and pregnancy in zero to 11.9 percent.
Among the 21 studies examining DVT, the pooled weighted mean prevalence of concomitant DVT at SVT diagnosis was 18.1 percent, ranging from 3.1 to 65.6 percent. Among the 14 prospective studies, the pooled prevalence of concomitant DVT was 24 percent (95% CI 18.9-30; p<0.001), while the seven retrospective studies had a pooled prevalence of 10 percent (95% CI 5.6-17.2; p<0.001).
Among the 11 studies examining PE, the pooled prevalence of concomitant PE at SVT diagnosis was 6.9 percent, ranging from 0.9 to 33 percent. Among the nine prospective studies, the pooled prevalence of concomitant PE was 8.2 percent (95% CI 4.3-14.9; p<0.001), while the two retrospective studies had a pooled prevalence of 3.6 percent (95% CI 2-6.4; p=0.347).
The researchers observed that the following risk factors were associated with SVT and concomitant DVT/PE:
- Active cancer
- Previous thromboembolic events
- Use of oral contraceptives
- Hormone replacement therapy
- Recent surgery
- Autoimmune diseases
A meta-regression analysis showed that female patients, those who had experienced recent trauma, and pregnant women had a lower prevalence of concomitant DVT/PE at the time of SVT diagnosis, while increasing age was a predictor of DVT/PE in SVT patients.
“Interestingly, when we specifically analyzed data from studies enrolling outpatients, female gender and recent trauma were confirmed as negative predictors of concomitant involvement of the deep venous system at the time of SVT diagnosis (p<0.001),” the authors noted.
Dr. Di Minno and authors proposed several possible explanations for the co-existence of SVT and DVT/PE, including the migration of the SVT toward the deep venous system, via the saphenofemoral junction (SFJ), the saphenopopliteal junction, or a perforating vein. Involvement of the SFJ was reported by 17.5 percent of SVT patients, suggesting it has a direct effect on the prevalence of deep venous system involvement.
Limitations of the analysis include the heterogeneity among the studies and the differences in the prevalence of concomitant risk factors for VTE among different study populations. In addition, the prevalence of DVT in this analysis was slightly lower than what previous large studies have found. There is also a risk of publication bias with this type of meta-analysis.
“The results of our large meta-analysis suggest that the prevalence of concomitant DVT and PE in patients presenting with SVT is not negligible,” the authors concluded. “Screening for a major thromboembolic event might be worthwhile in some ‘high-risk’ SVT patients, to allow adequate anticoagulant treatment to be planned.” Further studies are needed to confirm these findings and to identify clinical and demographic predictors of the presence of DVT/PE in SVT patients, they added.
Di Minno MND, Ambrosino P, Ambrosini F, et al. Prevalence of deep vein thrombosis and pulmonary embolism in patients with superficial vein thrombosis: a systematic review and meta-analysis. J Thromb Haemost. 2016;14:964-72.