The term thrombelastograph (TEG) was used to describe the trace produced from the measurement of the viscoelastic changes associated with fibrin polymerization. Recently the term rotational thromboelastometry has been applied to the output of the ROTEM instrument. Since its first description in 1948, the TEG/ROTEM has been successfully used in the near patient assessment of haemostasis. The greatest use has been the application of TEG-guided transfusion of blood components in hepatic and more widely in cardiac surgery. Recent years have seen a renewed interest in the technology with applications for both pharmaceutical monitoring and patient screening being described. The present review gives a broad overview of the developments and applications related to thrombelastography/thromboelastometry.

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Summary.  Background: Measurement of thrombin generation by calibrated automated thrombography (CAT) could fulfill the requirements of a global test of coagulability and is potentially applicable to routine clinical laboratory practice. The purpose of this study was to determine if corn trypsin inhibitor (CTI) could be used to abolish contact factor activation in this assay, thus allowing accurate measurement of low tissue factor (TF) concentration‐triggered thrombin generation on samples taken in a routine clinical setting. Methods: The endogenous thrombin potential (ETP) was measured by CAT. Results: The study demonstrated that addition of CTI after plasma separation is not sufficient and blood must be drawn into tubes containing CTI if in‐vitro contact factor‐activated thrombin generation is to be abolished. Contact factor‐activated thrombin generation is completely inhibited at a CTI concentration of 18.3 µg mL−1 whole blood. Increasing the CTI concentration above this level does not lead to suppression of the TF‐triggered ETP. At a TF concentration of 2 pmol, ETPs were significantly lower in the presence of CTI (P < 0.001). The difference (no CTI minus CTI) between results ranged from − 1 to 2159 nM min−1 (median − 754). Whilst the low concentration TF‐ETP assay was not optimized to distinguish degrees of coagulability between patient samples, there was a significant difference in ETP between normal and hemophilia samples and samples from patients with a clinical prothrombotic tendency. Conclusions: CTI can be applied to ETP measurement by CAT. This permits the use of CAT in a low TF‐triggered thrombin generation assay without concern for the effect of interference from in‐vitro contact factor activation and the optimum reagent conditions for using CAT as a global test of coagulability in clinical practice can now be defined.

SummaryMeasurement of the thrombin generating potential could provide a method for quantifying the composite effect of multiple risk factors. This study assessed the risk of a first as well as a recurrent venous thrombotic event associated with an increased endogenous thrombin potential (ETP). Analyses were performed in 360 patients and 404 control subjects of the Leiden Thrombophilia Study. The ETP was measured directly using a fluorogenic assay (Thrombinoscope TM ). Individuals with an increased ETP, i.e. above 90th percentile measured in control subjects (>2109AE0 nMAEmin) had a 1AE5-fold [95% confidence interval (CI): 0AE9-2AE3] increased risk of a first deep venous thrombosis. The risk was more pronounced after the analysis was restricted to idiopathic thromboses, i.e. 1AE7-fold (95% CI: 1AE0-2AE8). Overall, the hazard ratio of a recurrent thrombotic event associated with a high ETP, adjusted for age, sex and oral anticoagulant use was 1AE1 (95% CI: 0AE5-2AE2). Thus, a high ETP was not associated with an increased relative risk of recurrent venous thrombosis. At present, the clinical relevance of the thrombin generation assay in predicting recurrent venous thrombosis remains uncertain.

To cite this article: Besser M, Baglin C, Luddington R, van Hylckama Vlieg A, Baglin T. High rate of unprovoked recurrent venous thrombosis is associated with high thrombin-generating potential in a prospective cohort study. J Thromb Haemost 2008; 6: 1720-5.Summary. Objective: To determine the predictive value of measurement of parameters of thrombin generation for unprovoked recurrent venous thrombosis. Methods: Measurements were made of thrombin generation in a prospective cohort study of 188 patients with a first episode of venous thrombosis that was unprovoked, or provoked by a nonsurgical trigger. Results: The endogenous thrombin potential (ETP) was the only parameter associated with unprovoked recurrent thrombosis in a multivariate model [hazard ratio (HR) 1.3 per 100 nmol L min )1 increase, 95% confidence interval (CI) 1.0-1.6]. Patients with a high ETP had a significantly higher rate of unprovoked recurrence than those with a low ETP (HR 2.9, 95% CI 1.3-6.6, cumulative recurrence at 4 years 27% vs. 11%). Patients with an unprovoked first event had a significantly higher rate of unprovoked recurrence than those with a provoking factor (HR 2.7, 95% CI 1.2-6.1), and in these patients there was a significantly higher rate of unprovoked recurrence in association with a high ETP (HR 4.0,. After adjustment for Ddimer, thrombophilia, sex, and whether or not the first event was unprovoked, a high ETP remained a significant predictor of recurrence (HR 2.6, 95% CI 1.2-6.0). Conclusions: This study demonstrates a high rate of unprovoked recurrent venous thrombosis in patients presenting with a first episode of venous thrombosis and a high ETP.