Thrombin generation tests

The recent development of semi-automated methods has revived interest in the thrombin generation test, a global assay that measures the overall tendency of a plasma sample to form thrombin after initiation of coagulation. The thrombin generation curve, which is characterised by a lag phase followed by the formation and subsequent inhibition of thrombin, reflects all three phases of coagulation (initiation, propagation and termination). However, the specific contribution of each coagulation factor or inhibitor to the assay outcome depends on the reaction conditions used (e.g. tissue factor concentration used to trigger coagulation, addition of thrombomodulin or activated protein C). Although several studies have shown a correlation between thrombin generation and the risk of bleeding or venous thrombosis, the application of thrombin generation assays to clinical decision-making is still hampered by standardisation problems. The present paper discusses these issues with particular reference to Calibrated Automated Thrombography.