Pooled citrated platelet-poor plasma from healthy subjects was spiked with edoxaban (0.02-3.65 渭M) or fondaparinux (0.15-1.18 渭M). Parameters of TG were calculated using Thrombinoscope鈩?software. PT ratios and aPTT were measured in the presence of different thromboplastin reagents. Exogenous anti-FXa was measured using Rotachrom HBPM (Stago) and a specific assay developed for direct FXa inhibitors (Hyphen BioMed).
Edoxaban exhibited a 3-fold greater concentration-dependent effect than fondaparinux across TG parameters (except endogenous thrombin potential). Edoxaban also produced a concentration-dependent prolongation of PT ratio and aPTT. The magnitude of concentration-dependent increase was related to thromboplastin reagent. In contrast to edoxaban, fondaparinux was inactive on these clotting tests. Linear correlations were observed between plasma concentration of edoxaban and anti-FXa activity and results of clotting time assays.
TG evaluation by the CAT method, coagulation tests, and anti-FXa and clotting assays demonstrated concentration-dependent effects of edoxaban. The PT and aPTT prolongation are reagent dependent; correction of PT ratio by international normalized ratio does not reduce variability in response. The greater effect of edoxaban vs. fondaparinux may be related to the broader activity of direct FXa inhibitors compared with indirect FXa inhibitors.