In this issue of Blood, Roach and colleagues show that individuals with prior superficial venous thrombosis are at increased risk of developing venous thromboembolism when exposed to acquired clinical risk factors.1 

Although superficial venous thrombosis was originally perceived as a benign disease with a self-limited clinical course, it is now recognized that this condition is often associated either with concomitant venous thromboembolism or with early development of deep vein thrombosis and pulmonary embolism.2-5  Further, Heit et al reported in 2000 that individuals with previous superficial venous thrombosis were more than 4 times more likely to develop future deep vein thrombosis or pulmonary embolism,6  and this finding has subsequently been confirmed by several investigators.7,8  However, because most individuals with superficial venous thrombosis do not develop venous thromboembolism, it has been difficult to know how best to use this information to risk stratify patients.

Prior research has shown that genetic thrombophilias only minimally increase the risk of venous thromboembolism in patients with a history of superficial venous thrombosis.8  In the report published in this issue of Blood, Roach et al use data from the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA) population-based case control study9  that enrolled 4956 consecutive patients between 18 and 70 years of age with a first symptomatic objectively confirmed deep vein thrombosis or pulmonary embolism, together with 6297 age- and sex-matched controls, to examine the risk of venous thromboembolism in individuals with a self-reported history of superficial venous thrombosis and various clinical risk factors. Acquired risk factors included in this analysis were surgery, pregnancy, plaster casting and hospitalization within 3 months of venous thromboembolism diagnosis or study enrollment, oral contraception or hormone replacement therapy within the preceding 1 month, and malignancy in the 5 years prior to the index event.

Clinical risk factors were categorized as mild (smoking or overweight), strong (surgery, hospitalization, plaster casting, or malignancy), or reproductive (oral contraceptive use, postmenopausal hormone replacement therapy, or pregnancy and the postpartum period). Consistent with previous reports, individuals with prior superficial venous thrombosis had a 6-fold increase in the risk of venous thromboembolism compared with those without a similar history. The odds ratio for venous thromboembolism was increased to 9 with the addition of a mild clinical thrombotic risk factor and to approximately 30 in those with a major risk factor and in women with reproductive risks. The highest risks in the latter 2 categories were seen in patients with previous superficial venous thrombosis undergoing surgery or requiring hospitalization and those using oral contraceptives. Although one cannot directly infer absolute risks from a case-control study, the authors use previously established background incidences to determine the impact of their findings on the thrombotic risks associated with various clinical risk factors. In individuals with prior superficial venous thrombosis, the calculated risks were 1 in 32 in those undergoing surgery, 1 in 27 for those requiring hospitalization, and 1 in 51 in oral contraceptive users.

Although this study has several strengths, including its large size, objective diagnosis of the index venous thromboembolic event, and similar method of data collection for patients and controls, there are important limitations. Most importantly, the 95% confidence intervals for many of the risk estimates are wide; the diagnosis of superficial venous thrombosis and occurrence of clinical risk factors are based solely on patient self-report, and no information was obtained on the location of the superficial venous thrombosis or on the temporal relationship between it and the various clinical risk factors or the diagnosis of venous thromboembolism.

The results of this study are not sufficient to allow physicians to confidently modify standard recommendations for thrombosis prophylaxis in patients with a history of superficial venous thrombosis undergoing surgery or requiring hospitalization or to recommend against oral contraceptive therapy in affected women. How best to incorporate a history of superficial venous thrombosis into prophylaxis risk stratification schemes and decision making about the use of hormonal therapy in these patients has yet to be determined. However, in the interim, individuals with prior superficial venous thrombosis and their treating clinicians should have a heightened awareness of the potential for developing venous thromboembolism in these clinical settings.

Conflict-of-interest disclosure: The author declares no competing financial interests.

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