Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis

Project managers

Prof. dr S.C. Cannegieter, Prof. dr F.R. Rosendaal, dr W.M. Lijfering, dr A. van Hylckama Vlieg


Anticoagulation clinics in Leiden, The Hague, Utrecht, Rotterdam, Amsterdam and Amersfoort

The aim of the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA) study, a large case-control study, is to investigate risk factors for venous thrombosis and to assess the risk of thrombosis associated with combinations of these risk factors.

Almost 5000 patients with a first episode of deep venous thrombosis or pulmonary embolism from Mach 1999 until September 2004 were included. Partners of patients were invited to participate as control subjects. Furthermore a random digit dialing control group was collected. All participants were asked to complete a questionnaire, which includes questions on surgery, immobilisation, obesity, travel, pregnancy, oral contraceptive use, and other possible risk factors for venous thrombosis. Three months after discontinuation of the oral anticoagulant therapy, participants were invited for an interview and a blood sample was drawn or a buccal swab collected. Common genetic defects encoding coagulation factors have been measured, such as the factor V Leiden mutation and the prothrombin 20210A mutation. Investigations are ongoing to discover new genetic mutations. Levels of coagulation and fibrinolytic factors as well as several other biomarkers have been measured in plasma.

The relative risk of venous thrombosis has been calculated for individual risk factors and for combinations of risk factors. The MEGA study is the largest study ever performed on aetiology of venous thrombosis. This is necessary since the combined effect of thrombotic risk factors can only be studied in a large study population. Combinations of several risk factors are further integrated in specific prediction models to determine which patients are at particular high risk in certain situations (e.g. during surgery, plaster cast, pregnancy, oral contraceptive use). This way we can identify individuals with a highly increased risk of thrombosis. This information can lead to preventive measures in those individuals with high risk scores.

The results of the MEGA study have led to several publications in major impact journals.