Towards individualizing anticoagulant therapy: understanding risk factors for thrombosis and bleeding

Abstract

Anticoagulant treatment for venous thromboembolism (VTE) currently follows a “one-size-fits-all” approach. This thesis proposes a shift toward personalized treatment by tailoring dosage or monitoring frequency based on individual risk, beginning with the identification of novel risk factors for thrombosis and bleeding during anticoagulation. In Part I, the effects of statins, anabolic steroids, and glucocorticoids were assessed to clarify VTE mechanisms. In Part II, transient and fixed risk factors for major bleeding were examined. Results from Parts I and II highlight that, despite significant progress, many knowledge gaps still exist that prevent the personalization of anticoagulant treatment. Quantitative protein mass spectrometry (QPMS), which quantifies hundreds of proteins, offers a promising tool for further progress. In Part III, the application of QPMS in bleeding and thrombotic disorders was discussed, and the levels of 270 proteins were measured in a large cohort of anticoagulant users to later assess associations with major bleeding and thromboembolism. This thesis lays the groundwork for broader QPMS applications in identifying novel biomarkers of thrombosis and bleeding. Establishing individual risk profiles will enable tailored strategies, such as dose adjustments or additional monitoring for high-risk patients. Ultimately, this will mark a step toward truly personalized anticoagulant therapy.