Surgery as a trigger for incident venous thromboembolism: results from a population-based case-crossover study

Background: Surgery is a major transient risk factor for venous thromboembolism (VTE). However, the impact of major surgery as a VTE trigger has been scarcely investigated using a case-crossover design. Aim: To investigate the role of major surgery as a trigger for incident VTE in a population-based case-crossover study while adjusting for other concomitant VTE triggers. Methods: We conducted a case-crossover study with 531 cancer-free VTE cases derived from the Tromsø Study cohort. Triggers were registered during the 90 days before a VTE event (hazard period) and in four preceding 90-day control periods. Conditional logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for VTE according to major surgery and after adjustment for other VTE triggers. Results: Surgery was registered in 85 of the 531 (16.0%) hazard periods and in 38 of the 2124 (1.8%) control periods, yielding an OR for VTE of 11.40 (95% CI 7.42-17.51). The OR decreased to 4.10 (95% CI 2.40-6.94) after adjustment for immobilization and infection and was further attenuated to 3.31 (95% CI 1.83-5.96) when additionally adjusted for trauma, blood transfusion and central venous catheter. In a mediation analysis, 51.4% (95% CI 35.5%-79.7%) of the effect of surgery on VTE risk could be mediated through immobilization and infection. Conclusions: Major surgery was a trigger for VTE, but the association between surgery and VTE risk was in part explained by other VTE triggers often coexisting with surgery, particularly immobilization and infection.