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Mixed DOACs and the DOAC Clotting Time Test

In a January 2023 letter to the editor, available from the publisher or your library as Exner T, Ellwood L, Dangol M, Favaloro EJ. Mixing factor Xa and thrombin inhibiting direct oral anticoagulants produces a synergistic prolonging effect on most clotting tests. Int J Lab Hematol. 2023 Feb 21. doi: 10.1111/ijlh.14043, investigators examined a DRVVT-based DOAC clotting time test’s [DCT] ability to measure the anti-Xa DOACs rivaroxaban, apixaban, and edoxaban and the anti-IIa [thrombin] DOAC dabigatran. Using in vitro spiking, the investigators also applied the assay to mixed DOAC preparations, including, of the highest interest, dabigatran mixed with each of the anti-Xas. The DCT test is described in a primary study available from Elsevier, Sennesael AL, Exner T, Chatelain B, et al. An optimized dRVVT-based assay to estimate the intensity of anticoagulation in patients treated with direct oral anticoagulants. Thromb Res. 2017 Sep;157:29-37. doi: 10.1016/j.thromres.2017.06.034. The DCT shows considerable promise as a general DOAC assay.
Comments (1)
Anticoagulant Therapy
Apr 10, 2023 6:22pm

Thanks George for highlighting this study. The main point of the study was to show that different classes of direct oral anticoagulants (DOACs), when added together, had a synergistic effect on clotting assays, beyond what might be expected based on the final concentration of DOACs. That is, adding a quantity of an anti-IIa DOAC (i.e., dabigatran) plus a quantity of an anti-Xa DOAC (e.g., rivaroxaban) to a final concentration of 200ng/mL had a much greater effect on inhibition of coagulation than did either 200ng/mL of either agent used alone. This synergy could be shown using a variety of clotting assays. We hypothesised that this may also be relevant to anticoagulant therapy, being likely reflective of more effective antithrombotic activity in combination, and somewhat analogous to what is done with dual anti-platelet therapy. Watch this space!

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