Thrombin generation, a function test of the haemostaticthrombotic system

TLDR

Evidence indicates that thrombogram parameters, especially endogenous thrombin potential, can assess bleeding or thrombotic risk and are altered by antithrombotic or haemostatic therapies, with increased thrombin generation linked to thrombosis and decreased generation linked to bleeding. The study aims to employ the thrombogram as a tool for discovering new antithrombotics and evaluating the haemorrhagic or thrombotic side effects of other drugs such as oral contraceptives. Using a fluorogenic thrombin substrate and continuous sample calibration, the thrombogram can be generated rapidly and accurately (<5% error), enabling high‑throughput assessment of thrombin generation in plasma with or without platelets. The thrombogram shows promise for clinical management of bleeding and thrombotic disease and for drug research, though current experience is insufficient to delineate its full limitations.

Abstract

Summary By the use of a fluorogenic thrombin substrate and continuous calibration of each individual sample, it is now possible to obtain a thrombin generation (TG) curve (or thrombogram) in plasma, with or without platelets, in an easy routine procedure at high throughput and with an acceptable experimental error (&lt; 5%). Evidence is growing that the parameters of the thrombogram, and notably the area under the curve (endogenous thrombin potential, ETP), are useful in assessing bleeding-or thrombotic risk and its modification by antithrombotic-or haemostatic treatment. Available data strongly suggest that conditions (congenital, acquired, drug-induced) that increase TG all cause a thrombotic tendency and that conditions that decrease TG prevent thrombosis but, beyond a limit, cause bleeding. Diminution of TG is a common denominator of all antithrombotic treatment, including anti-platelet drugs. The thrombogram can also be used as a tool in the search for new antithrombotics and reflects the haemorrhagic or thrombotic side effects of other drugs (e.g. oral contraceptives).The thrombogram thus is a promising new approach to clinical management of bleeding and thrombotic disease as well as a tool in drug research and epidemiology. Our experience at this moment is insufficient, however, to already clearly define its limits.