Measuring direct oral anticoagulants in standardized fully automated thrombin generation on CeveronĀ® alpha

L. Wagner1, E. Wimmer2, J. Seier2, N. B. Binder1, A. C. Haushofer2 (1Vienna, Austria, 2Wels, Austria)

Laboratory tests
Date: 17.02.2017,
Time: 17:15 - 18:15

Objective: The increasing use of the direct oral anticoagulants (DOAC) creates the need of their measurement in clinical routine. A modified thrombin time-based assay can be used for the measurement of thrombin inhibitors and the direct Xa inhibitors can be measured with a chromogenic anti-Xa assay. However, these assays only measure the initiation phase of the coagulation cascade. In the present wanted to see if the thrombin generation assay (TGA), which measures the entire thrombin generation process, could be used to better discriminate the inhibitory profile of the DOACs in patients

Methods: For this proof of concept study, platelet-poor plasma spiked with Apixaban, Rivaroxaban, Dabigatran, Arixtra or LMWH as well as Phenprocoumon plasma with different INR values was tested in the TGA. As initiators of thrombin generation two triggers differing in phospholipid concentrations were used. Analysis was performed on the coagulation analyzer CeveronĀ® alpha TGA.

Results: All anticoagulants, except Dabigatran, which only shows a response at higher doses, inhibited thrombin generation in a concentration-dependent manner after activation with both triggers, influencing all TGA parameters. Percent inhibition was calculated for Peak Thrombin (Peak) and Area under the Curve (AUC) values. For the Xa inhibitors Rivaroxaban and Apixaban the inhibition of Peak values was more pronounced as for AUC, showing a plateau for both parameters at DOAC concentrations above 200ng/mL, were as for high heparin concentrations and INR values at 4.5 both parameters showed almost complete inhibition. Dabigatran showed a 6-fold prolongation of the Lag time, inhibition of Peak and AUC was below that for Xa inhibitors.

Conclusion: Differences in TGA parameters between the anticoagulants reflect their differing inhibiting capacity in human plasma. Thrombin generation measurement in samples with DOACs at clinically relevant plasma levels could therefore serve as a fine-tuned indicator for hemostatic balance (individualized therapy) in patients using the DOACs.