Thrombosis and hemostasis

Over the past years, the research into venous thrombosis has been instrumental in the discovery of factor V Leiden, a common genetic prothrombotic abnormality, and several other hitherto unknown risk factors for thrombosis (prothrombin 20210A, high levels of factor VIII, IX, II, XI). Similarly, collaborations with the department of Hematology and the department of Obstetrics and Gynecology has led to quantification of the thrombotic risk associated with use of oral contraceptives, a common environmental risk factor. Integration of these findings led to the observation that carriers of factor V Leiden have a greatly increased thrombotic risk when using oral contraceptives (gene-environment interaction).

A major future aim is to fine-tune our knowledge of thrombotic risk, the main question being: why does this patient develop thrombosis today? The answer to this question depends on further knowledge of risk factors for thrombosis. Subsequently, the interaction of all possible combinations of risk factors needs to be known. One of the studies to answer this question is a very large case-control study, including over 5000 participants (the MEGA study). The data collection of this study has been completed, and several researchers are now using it to identify new genetic and environmental risk factors for venous thrombosis.

Recent research has focussed on the association between air travel and thrombosis. In the WRIGHT project, performed under the auspices of the WHO in collaboration with the AMC and researchers from the United Kingdom and Switzerland, we established the risk of thrombosis after long-haul travel in large groups of travellers. More importantly, we identified individuals with a clearly increased risk during travel, such as very tall, short or obese people, women using oral contraceptives and individuals with clotting abnormalities, such as factor V Leiden. In an experiment in an actual airplane, we found out that not only immobilisation, but also cabin-related factors, such as hypobaric hypoxia, may contribute to risk. Currently, new studies are designed to investigate safe and effective methods to prevent thrombosis after long distance travel.

Several projects focus on the risk of recurrent venous thrombosis, which is several percent per year. Current laboratory tests are poor predictors of recurrent thrombosis, and together with the university of Cambridge we are conducting a study to assess the value of global clotting tests in predicting recurrent venous thrombosis. In addition, we participate in studies looking into the value of testing for prothrombotic abnormalities in patients and their families.