Role of thromboelastography and rapid thromboelastography to assess the pharmacodynamic effects of vitamin K antagonists

Abstract

Thromboelastography (TEG) measures the effects of antithrombotic agents by assessing global functional clotting status by evaluating the viscoelastic properties of in vitro clot formation. Recently, rapid TEG (r-TEG), which uses tissue factor in addition to standard kaolin to accelerate activation of the clotting cascade, has been proposed to obtain more immediate results. The correlation between results of TEG or r-TEG with international normalized ratio (INR) in patients on vitamin K antagonist (VKA) therapy has not been explored and represents the aim of this study. Patients on chronic therapy with VKAs (n = 100) were included in an observational prospective pharmacodynamic study. The correlation between TEG parameters, in particular markers of thrombus generation [Reaction time (R), maximum rate of thrombus generation (MRTG), and time to maximum rate of thrombus generation (TMRTG)], and INR values as well as the concordance between these parameters and therapeutic INR ranges were evaluated. In addition, in a subgroup of subjects (n = 17), the correlation of r-TEG parameters with TEG parameters and INR values was also assessed. No correlation was found between INR and TEG parameters of thrombus generation, in particular between INR and R (r = 0.189, p = 0.06), MRTG (r = -0.027, p = 0.79), and TMRTG (r = 0.188, p = 0.06). Further, no concordance was found between these parameters and recommended INR ranges. Significant Spearman correlations were found between INR and activated clotting time (rS = 0.546, p < 0.001), r-R (rS = 0.572, p = 0.017), and r-TMRTG (rS = 0.510, p = 0.037), but not r-MRTG (rS = 0.131, p = 0.617). Results were obtained in 24 ± 6 versus 12 ± 4 min with TEG and r-TEG, respectively (p < 0.001). In patients on chronic VKA therapy, TEG is not a useful tool to evaluate VKA anticoagulant effect, compared with standard INR measurements. However, r-TEG parameters of thrombus generation correlate with INR levels, suggesting a possible role of this assay for measuring more expeditiously anticoagulant treatment effects.

Viscoelastic monitoring in trauma resuscitation

“…162 Detection of warfarin and novel oral anticoagulants (NOACs) is similarly unreliable, due to the fact that the test is run with added reagents that mask the presence of an anticoagulant. [163][164][165] Titrated NOAC added to blood samples ex vivo can be used to develop a standard curve for VEM assays, 166 and in other studies, well defined cohorts of patients taking a single drug had blood collected at a prescribed interval post-administration with effective differentiation of drug vs placebo. [167][168][169] Unfortunately, these experiments are limited by the homogeneity of samples assessed and development of real-world thresholds in the setting of trauma with variable renal function and unknown dose administration time, agent, etc.…”

Proteomics in Diagnosis: Past, Present and Future

“…As discussed being a cumbersome and time consuming technique 2DE could not reach the clinics, however, Mass spectrometry, especially MALDI-TOF have successfully made its way to pathology labs in the present decade. Several diseases like cancer, Alzheimer's disease, Amyloid lateral sclerosis, renal amyloidosis, and Severe combined immunodeficiency can now be diagnosed using mass spectrometry and its variants [28][29][30][31][32][33][34].…”

Review of Thromboelastography in Neurocritical Care

“…Small studies thus far have differing results regarding the utility of TEG in patients on oral anticoagulants. For instance, Franchi et al demonstrated that in 100 patients taking vitamin K antagonists (VKA) there was a correlation between the following r-TEG times and INR: ACT, R time, time to maximum rate of thrombus generation (TMRTG) time, but not with the maximum rate of thrombus generation (MRTG) time [16]. Rathbun et al, however, performed a prospective study of 22 patients taking rivaroxaban, and demonstrated no correlation to TEG findings [17].…”

“…Summary of papers chosen for discussion Castilo et al[16] 64 patients with ICH compared to human controls. ICH patients had faster clot formation compared to controls.…”