Clinical implications of deficiencies of protein S, protein C or antithrombin

The last decade a growing number of studies have addressed the multicausality of venous thromboembolism (VTE). The development of VTE results from interactions between multiple genetic and environmental risk factors. A number of thrombophilic risk factors have been identified, which can be subdivided into strong or mild risk factors. The strong risk factors include lupus anticoagulant, anticardiolipin antibodies, and deficiencies of protein S, protein C or antithrombin. Factor V Leiden, the prothrombin G20210A mutation, high levels of factor VIII, IX and XI and hyperhomocysteinemia can be classified as mild risk factors. Mild risk factors are important for the risk in the general population, but less important for the individual patient. Clinical impact for the individual patient is mainly dependent on the absolute risk of merely strong risk factors. Therefore, this thesis primarily deals with the absolute risk of VTE and arterial thromboembolism (ATE) in patients with the most serious risk factors. Additionally, not only the risk of single deficiencies was studied, but also the impact of combinations of hereditary and/or exogenous factors was analysed.