E-coagulation: applied coagulation systems biology to accurately assess the hemostatic balance of individual patients

The blood coagulation system consists of an intricate set of reactions that protect the body from bleeding and thrombosis. In general, the system is well-balanced and excessive bleeding or runaway coagulation in an individual are not daily events, but the life-time risk of a single event is nevertheless high. In cases with profound inherited or acquired imbalances in the coagulation system (e.g. hemophilia, deficiencies of natural anticoagulants, auto-antibodies against coagulation proteins, lupus anticoagulants, severe acute infection, etcetera) it is relatively easy to diagnose the increased risk of bleeding or thrombosis and to take prophylactic measures in the form of anticoagulant drugs or coagulation factor supplementation. Much more difficult is tailoring anti-coagulant or pro-coagulant treatment in primary or secondary prevention of thrombosis or bleeding of a more episodic nature. Therefore, there is a strong demand for improved measures of the hemostatic balance that can be used to determine with more precision thrombosis and bleeding risks in an individual person. In this project we aim to discover a combination of measurements that together accurately reflect the coagulant status of individual patients at risk of bleeding or thrombosis. Optimal combinations of coagulation tests will be estimated using a computational model of coagulation, based on true-life measurements of the hemostatic balance within the context of venous thrombosis and hemophilia. Additional dynamic data to statistically estimate the parameters of this model will be obtained from in vitro studies of blood platelet and vessel wall functions. Finally, predictive performance of the combination of measurements will be evaluated within the context of recurrent venous thrombosis and of bleeding under anti-coagulant treatment.