Different roads lead to venous thrombosis after lower-leg injury and knee arthroscopy: mechanistic insights in the development of venous thrombosis

Abstract

Lower-leg cast immobilization and (elective) knee arthroscopy are associated with increased risk of symptomatic venous thrombosis, i.e., 2% and 0.6%, respectively. Currently applied thromboprophylaxis strategy, with low-molecular weight heparin, were found to be not optimal in both patient groups. In order to improve this, knowledge about underlying mechanisms for hypercoagulability following lower-leg cast application and knee arthroscopy is indispensable. However, as yet, this is not well understood. In this thesis, we established the effect of lower-leg trauma and knee arthroscopy on the coagulation system. We found that lower-leg trauma induces endothelial activation, hyperinflammation and a shift of the haemostatic balance towards a hypercoagulable state. Endothelial activation and hypercoagulability after lower-leg trauma are associated with the risk of venous thrombosis in the first three months. For knee arthroscopy, on the other hand, we did not detect any changes in plasma which point in the direction of thrombus formation. It becomes clear that in both situations, different mechanistic pathways of the development of venous thrombosis are involved. The knowledge provided by this thesis can be considered as the first step in the exploration of novel prevention targets for venous thrombosis and potential biomarkers for prediction of venous thrombosis in both patient populations.