The Role of Surgery as a Trigger for Incident Venous Thromboembolism

Abstract

Background: Venous thromboembolism (VTE) is a collective term for deep vein thrombosis and pulmonary embolism. Surgery is a major and well-established transient risk factor (i.e. trigger) for VTE in the general population. However, the impact of major surgery on the risk of VTE has not been thoroughly investigated when other concomitant VTE triggers are also taken into account.

Aim: The aim of this thesis was to investigate the role of major surgery as a trigger for incident VTE using a case-crossover design while adjusting for other VTE triggers.

Methods: A population-based case-crossover study comprising 707 incident VTE cases derived from the Tromsø Study was conducted. Triggers were registered during the 90 days before a VTE event (hazard period) and in four preceding 90-day control periods. Odds ratios (ORs) for VTE was calculated using conditional logistic regression with 95% confidence intervals (CIs) according to the presence of major surgery. A mediation analysis was performed to determine the other VTE triggers’ potential to mediate the effect of surgery on VTE risk.

Results: Surgery was registered in 118 (16.7%) of the 707 hazard periods and 88 (3.1%) of the 2828 control periods, yielding an OR for VTE of 6.95 (95% CI: 5.08-9.50). The OR decreased to 2.21 (95% CI: 1.43-3.40) after adjustment for immobilization and infection and was further attenuated to 1.49 (95% CI: 0.92-2.40) when additionally adjusted for trauma, red blood cell transfusion and central venous catheterization. In the mediation analysis, approximately 70% of the total effect of surgery on VTE risk could be mediated through immobilization and infection.

Conclusions: In this case-crossover study, major surgery was a trigger for VTE, but the association between surgery and VTE risk could be largely explained by concomitant factors related to surgery, particularly immobilization and infection.