Clinical Thrombosis and Haemostasis

The diagnosis and mechanisms of (recurrent) venous and arterial thrombosis are being studied in cohort studies in consecutive patients with deep venous thrombosis (DVT), myocardial infarction, stroke, or other pathologies resulting in a hypercoagulable state. Related to antithrombotic therapy we are involved in a number of multicenter trials that explore the efficacy and safety of new specific anticoagulant agents including idraparinux and dabigatran. At this stage we have optimized and validated a thrombin generation assay (Calibrated Automated Thrombogram) for use in routine clinical settings, as well as several new methods to determine the contribution of activation of blood coagulation factors XII and XI to thrombotic risk. The development and validation of new assays is currently ongoing and new patient cohorts are included in collaboration with many investigators from both our own organization and external institutes.

The mechanisms by which coagulation proteins and their inhibitors influence cellular interactions are studied, are being employed in animal models. In these models we administered either active site inhibited factor seven (ASIS) or activated protein C (APC) to study the mechanisms leading to diminished organ injury. Current studies indeed confirm that inhibition of coagulation limits myocardial damage and that several pathways are involved. In a mouse model of atherosclerosis we explore the effects of prolonged inhibition of thrombin vis a vis the effects of genetically altered thrombin production on the development of accelerated atherosclerosis.

Using both in vitro experiments and animal as well as human volunteer models we study the effects of exposure to particulate matter (air pollution) on activation of coagulation and the risk of atherothrombosis.