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.
Essentials
The value of thrombin generation assay (TGA) in monitoring direct oral anticoagulants (DOAC) is not well defined.TGA parameters were measured and correlated to DOAC levels in 10 healthy volunteers after oral intake of DOACs.Lag time is the only sensitive TGA parameter across different DOACs, dabigatran, rivaroxaban and apixaban.Endogenous thrombin potential had weak correlation with DOAC levels and not suitable as stand‐alone parameter.
BackgroundThere are clinical situations where monitoring direct oral anticoagulants (DOACs) may be useful. The clinical application of thrombin generation assay (TGA) in monitoring the effect of DOACs has not been well established. An ex vivo study was performed to systematically evaluate the anticoagulant effect of dabigatran, rivaroxaban and apixaban on each individual TGA parameter through serial measurements over time to assess suitability of these parameters for monitoring the anticoagulant effect of DOACs.MethodsTen healthy volunteers were given oral dabigatran 150 mg, rivaroxaban 20 mg, or apixaban 10 mg once. TGA parameters lag time, endogenous Thrombin potential (ETP), and thrombin peak height, time to peak, and velocity index were measured at times 0, 2, 4, and 24 hours after intake of DOAC. TGA parameters and DOAC concentrations were correlated.ResultsThe lag time was significantly correlated with all DOAC concentrations (r ≥ .81, P < .0001 for all). Thrombin peak height best correlated with direct Factor Xa inhibitor (FXa) concentrations in nonlinear fashion (R² ≥ .87). ETP was weakly correlated with DOAC levels (r ≤ .68). Besides lag time, the other TGA parameters were not significantly altered over time by dabigatran.ConclusionLag time was the only sensitive TGA parameter across the different classes of DOACs evaluated. Thrombin peak height was strongly correlated to FXa inhibitor concentrations and potentially a useful parameter to monitor FXa inhibitors at low concentrations. ETP had a weak correlation with achieved DOAC concentrations and is likely less suitable for assessment of DOAC effect as a stand‐alone parameter.
Background: Direct-acting oral anticoagulants (DOACs) do not require monitoring. Measurement of DOAC effect would be useful in the event of bleeding, trauma, and thromboembolism while on anticoagulation. We evaluated the effectiveness of the investigational DOAC assays on the TEG®6s Hemostasis Analyzer to assess the anticoagulant effect of DOACs in patients treated for atrial fibrillation or DVT.
Methods: Patients on treatment for a minimum of 7 days with standard doses of dabigatran, rivaroxaban and apixaban were included. DOAC plasma concentrations and TEG®6s R-time were measured and correlated. The sensitivity, specificity and negative predictive value (NPV) of R-time to detect DOAC concentrations of ≥ 30, ≥ 50 and ≥ 100 ng/mL were calculated.
Results: 189 Subjects were included, (n=50) on apixaban, (n= 62) on rivaroxaban, (n=53) on dabigatran and (n=24) on no DOAC were studied. Using the direct thrombin inhibitor (DTI) channel, R-time demonstrated strong linear correlation with dabigatran levels (r = 0.93, p < 0.0001). Using the anti-factor Xa (AFXa) channel, R-time demonstrated strong non-linear correlation with rivaroxaban and apixaban levels (rs = 0.92 and 0.84 respectively, p < 0.0001 for both). R-time revealed strong sensitivity and NPV in detecting low DOAC levels for the predefined concentrations.
Conclusion: R-time measured by TEG®6s DOAC Specific cartridge has a strong correlation with concentrations of the most commonly used DOACs, with high sensitivity and NPV for detecting lower drug levels that are considered clinically relevant for patients in need of antidote, or prior to urgent surgery. Further studies to determine the relation of R-time to clinical outcomes are warranted.
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