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

Abstract

Thromboelastography is useful for assessment of whole blood coagulation. The objective of this study was to evaluate the possibility of linking the tracing of whole blood clotted in a thromboelastograph TEG 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 8 channels of a TEG system. At different time points the whole blood TEG reaction cups were put in a cold quenching solution, centrifuged, and the supernatants were kept at −80°C until assayed for TAT by ELISA. Total Thrombus Generation (TTG) was calculated from the first derivative of the TEG waveform and was compared to thrombin generation measured by TAT. The two vectors of values -the TAT thrombin generation data and the corresponding TEG TTG -were analyzed using Pearson correlation coefficients and linear, non-linear, and natural log (Ln) transformation of TAT values for leastsquares goodness-of-fit curves. The best least-squares fit is an exponential curve. Linearizing using the natural log of the TAT thrombin generation variable produces the same R 2 as for the exponential curve. The prediction equation is y = 8.0465 + 0.0005x (P≤ 0.0001), where y is the TAT thrombin generation in the Ln transformation variable and x is the TEG TTG variable. The high magnitude of R 2 and the high significance of the prediction equation demonstrate the high efficacy of the prediction of TAT thrombin generation using the TEG TTG.

Monitoring Recombinant Factor VIIa Treatment: Efficacy Depends on High Levels of Fibrinogen in a Model of Severe Dilutional Coagulopathy

“…11 Recently, modified parameters of the thrombelastograph/thrombelastometry have been introduced based on the first derivative of the original tracing and been shown to correlate closely with thrombin formation. 11,23 These parameters, time to maximum thrombus generation (t-MaxVel) maximum rate of thrombus generation (MaxVel), and total thrombus generation (area under the curve, AUC) are supposed to be more sensitive to rFVIIa treatment than standard thrombelastography/thrombelastometry parameters. 26 However, these modified parameters did not better perform in monitoring rFVIIa administration in the present study compared to ROTEM's conventional α-angle and MCF as well as Sonoclot's CR.…”

“…16,[23][24][25] In order to study thrombus generation, modified ROTEM parameters (based on the original tracing) have been introduced recently: maximum velocity of clot formation (maximum rate of thrombus generation, MaxVel), time to reach MaxVel (time to maximum thrombus generation, tMaxVel) and total thrombus generation (area under the curve, AUC). 11,23 These parameters are supposed to be more sensitive to rFVIIa than standard ROTEM parameters. 26 The Sonoclot Analyzer provides information on the entire hemostasis process both in a qualitative graph, known as Sonoclot Signature and as quantitative results: the activated clotting time (ACT), the clot rate (CR) and the platelet function.…”

Tests of global haemostasis and their applications in bleeding disorders

“…A critical preanalytical issue is the collection of blood without contact activation. The same precautions mentioned above for sample collection using CTI in the collection tubes also apply to samples collected for thromboelastography [31]. The source and amount of CTI can also be an issue when very low concentrations of tissue factor are used for the test.…”

Perioperative coagulopathy monitoring

“…Consensus guidelines have been published for these off-label indications, but it is still unclear how to reliably monitor patients receiving rVIIa [39]. To better study the result of thrombin generation, modified TEG/ROTEM parameters based on the first derivative of original TEG/ROTEM tracing have been introduced recently: maximum velocity of clot formation (MaxVel), time to reach MaxVel (tMaxVel), and total thrombus generation (area under the curve) [40,41]. These parameters may be more sensitive to rVIIa than standard TEG/ROTEM parameters [42].…”