Background: Reversible, direct factor Xa inhibitors (Xa-DOACs) are used frequently in clinical practice, and concern Rivaroxaban, Apixaban, and Edoxaban.
Aims: We studied the effects in the thrombodynamics method on clot growth, and on thrombin generation.
Methods: Thrombodynamics with spiked plasma samples, recording layer thickness and thrombin formation.
Results: In clot growth the Xa-DOACSs, all similarly, inhibited stationary growth rate partially (50-45%) in normal plasma and not at all in factor IX and VIII deficient plasma up to high concentrations of 4 µM.
The thrombin generation close to the surface-bound tissue factor in the thrombodynamics, showed an inhibition with IC-50 ~ 2.5 µM. The thrombin generation further from the surface (intrinsic TG), depending on the factor XI-VIII-IX route was dose-dependently inhibited to a maximum of 60% inhibition.
We can take advantage of this specific inhibition to determine the contribution of extrinsic and intrinsic factor Xa formation in individuals.
In 10 apparently normal, young individuals we determined both portions of factor Xa activation and arrived for the fibrin layer thickness after 5000 secs at total layer thickness 2896 µm (SD 20%) and for the apixaban sensitive portion at 1666 µm (SD 17%) and the inhibited portion at 1230 µm (SD 44%). The extrinsic portion shows less interindividual variability (CV 17%) compared to the intrinsic portion (CV 44%). The variable intrinsic portion integrates contributions of factors XI, IX and VIII.
Conclusions: In view of the relationships between elevations of factors XI, IX and VIII in epidemiological studies, we consider the specific, integrated testing of the intrinsic portion relevant for thrombosis. On the other hand, the relation of decreases in those factors in relation to bleeding also renders this test relevant in this respect.
To cite this abstract in AMA style:Kluft C, Naji S. Reversible Factor Xa Inhibitors Specifically Inhibit, in Clot Growth, via the Intrinsic Tenase Complex: A Tool to Determine Specifically the In- and Extrinsic Contribution to Clot Growth [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 1). https://abstracts.isth.org/abstract/reversible-factor-xa-inhibitors-specifically-inhibit-in-clot-growth-via-the-intrinsic-tenase-complex-a-tool-to-determine-specifically-the-in-and-extrinsic-contribution-to-clot-growth/. Accessed September 24, 2021.
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