Fully automated thromboelastograph TEG 6s to measure anticoagulant effects of direct oral anticoagulants in healthy male volunteers

Abstract

Background The ability to assess the hemostatic effect of the direct oral anticoagulant (DOACs) may be valuable in clinical situations such as bleeding or thrombosis, before urgent surgery, or reversal of anticoagulation. We sought to assess the anticoagulant effect of DOACs with the new‐generation fully automated thrombelastograph TEG 6s using resonance‐frequency viscoelasticity measurements and disposable multichannel microfluidic cartridges. Methods A single dose of oral dabigatran 150 mg, rivaroxaban 20 mg, or apixaban 5 mg was given to 9 healthy males. Phlebotomy was performed at 0, 1, and 3 hours after administration of DOAC. TEG parameters were measured using TEG_6s. Concentrations of DOACs were measured using chromogenic assays. The TEG parameters were correlated to the DOAC concentrations. Results The reaction time (R) demonstrated the strongest response to DOAC intake. There were no correlations between other TEG parameters and DOAC concentrations. Using the direct thrombin inhibitor (DTI) channel, R was significantly correlated with dabigatran levels (r = 0.94, P < 0.0001). Using the anti–factor Xa (AFXa) channel, R was significantly correlated with rivaroxaban and apixaban levels (r = 0.93 and r = 0.83, respectively; P < 0.0001 for both). R >2.5 minutes for dabigatran (DTI channel), >2.5 minutes for apixaban, and >1.8 minutes for rivaroxaban (AFXa channel) were associated with 100% sensitivity and ≥ 90% specificity to detect DOAC levels of ≥ 50 ng/mL. Conclusion We have demonstrated that TEG_6s R has significant correlation with DOAC blood concentrations and has potential for monitoring the DOAC's effect on hemostasis with reasonable sensitivity in the small sample analyzed. This novel technology is easy to use on a small volume of whole blood without requiring a specialized laboratory. Further study is warranted to correlate R with clinical outcomes.

Effect of Dabigatran on Clotting Time in the Clotpro Ecarin Clotting Assay: A Prospective, Single-Arm, Open-Label Study

“…Studies have been performed with a developmental TEG 6s cartridge, where one channel with ecarin enables detection of dabigatran and another channel allows detection of FXa inhibitors. 18 , 30 TEG 6 s and ROTEM sigma each have 4 channels. With ClotPro, there are 6 channels and therefore a larger number of tests can be performed simultaneously.…”

Developing Deep Venous Thrombosis while on Rivaroxaban: A Review of Rivaroxaban

“…But this study was limited in terms that the R-value was measured only 3-time points over 3 hours rather than more time points over 12 to 24 hours and only on nine healthy young males [40]. This study reflected that DOACs primarily affect the whole blood clotting time [40].…”

“…Therefore, this can be potentially used in presurgical patients receiving DOAC, including situations prior to cardioconversion or radiofrequency ablation procedures [40]. But this study was limited in terms that the R-value was measured only 3-time points over 3 hours rather than more time points over 12 to 24 hours and only on nine healthy young males [40]. This study reflected that DOACs primarily affect the whole blood clotting time [40].…”

“…Also, the R-value had enough sensitivity and specificity to detect low DOAC concentrations. Therefore, this can be potentially used in presurgical patients receiving DOAC, including situations prior to cardioconversion or radiofrequency ablation procedures [40]. But this study was limited in terms that the R-value was measured only 3-time points over 3 hours rather than more time points over 12 to 24 hours and only on nine healthy young males [40].…”

Can We Measure the Individual Prothrombotic or Prohemorrhagic Tendency by Global Coagulation Tests?

“…179 Recently, the TEG 6s has been assessed for the monitoring of DOACs. 180 It was demonstrated that the R parameter was the most sensitive and correlated with the DOAC concentration when assessed via the specific cartridge for factor Xa or thrombin inhibitors. 180 The predictive value of this assay was reported to be very high (>98%), which is particularly important in emergency situations.…”