Thrombin generation assay and other universal tests for monitoring haemophilia therapy

Factor VIII bypassing agents have different multiple modes of action, but share the common feature of inducing or facilitating thrombin generation. The information obtained from most overall assays to measure the haemostatic response to inhibitor-bypassing agents is limited to the initial phase of blood coagulation (clotting time measurement) or the formation of a solidifying clot followed by fibrinolysis (thrombelastography), and excludes the real endpoint of thrombin generation. Thrombin generation assays (TGAs) measure the whole kinetics of thrombin generation even after the clot formation, and thus assess all activating and inactivating systems of coagulation. Therefore, TGAs are not only becoming a universal tool to improve understanding of haemostasis and to investigate biochemical principles of the haemostatic system, but are also evolving as a powerful prognostic and monitoring tool for inhibitor bypassing therapies.