Evaluation of the profile of thrombin generation during the process of whole blood clotting as assessed by thrombelastography

Abstract

The objective of this study was to evaluate the possibility of linking the tracing of whole blood clotting in a thrombelastograph® (TEG®) hemostasis system with the generation of thrombin assessed by thrombin/antithrombin complex (TAT). Citrated whole blood containing corn trypsin inhibitor from volunteers was clotted in the presence of CaCl 2 and tissue factor. Clotting was monitored with the eight channels of a TEG® system. At different time points, the whole blood TEG® reaction cups were kept in a cold quenching solution, centrifuged, and the supernatants were kept at -80 °C until assayed for TAT by ELISA. The total thrombus generation (TTG) was calculated from the first derivative of the TEG® waveform and was compared with thrombin generation measured by TAT. The two vector values - the TAT thrombin generation data and the corresponding TEG® TTG - were analyzed using Pearson correlation coefficients (r) and linear, non-linear and natural log (In) transformation of TAT values for least-squares goodness-of-fit curves. The best least-squares fit is an exponential curve. Linearizing using the In of the TAT thrombin generation variable produces the same r (0.94) as of the exponential curve. The prediction equation is y = 8.0465 + 0.0005x (P ≤ 0.0001), where y is the TAT thrombin generation variable in the In transformation and x is the TEG® TTG variable. The high magnitude of r and the high significance of the prediction equation demonstrate the high efficacy of the prediction of TAT thrombin generation by the use of TEG® TTG. © 2005 International Society on Thrombosis and Haemostasis.