Direct oral anticoagulants in point-of-care monitoring: an ex-vivo study.

Abstract

Anticoagulatory activity of direct oral anticoagulants (DOACs) is not routinely measurable by point-of-care monitoring. Thus, the aim of this study was to evaluate the influence of dabigatran/rivaroxaban on point-of-care testing. Samples from 34 participants under DOAC therapy were drawn at two time points. Before ingestion and two-to-three hours afterwards. Thrombelastometric (ROTEM) and aggregometric (Multiplate) measurements were performed. Dabigatran and rivaroxaban plasma levels were determined. Dabigatran and rivaroxaban plasma levels showed significant correlations with clotting time (CT) in EXTEM (r=0.765, P<0.0001; r=0.689, P<0.0001) and INTEM (r=0.792, P<0.0001; r=0.595, P<0.001). A positive correlation was identified between dabigatran ingestion and maximum-clot-firmness (MCF) (r=0.354, P<0.05) in the EXTEM test, pronounced in the absence of concomitant antiplatelet therapy (r=0.709, P<0.05). EXTEM-MCF positively correlated with the TRAP test in aggregometry (0.662, P<0.05), an effect not observed in patients treated with antiplatelet therapy. Prolongation of CT-EXTEM and CT-INTEM indicates delayed initiation of clot formation. The CT-EXTEM seems to facilitate qualitative monitoring of dabigatran. In contrast, qualitative monitoring of rivaroxaban by CT-EXTEM may be limited as rivaroxaban may affect the measurement at therapeutic plasma levels. It seems that clot formation is faster/firmer in the presence of increased dabigatran plasma levels. This can be attributed to a non-dose-dependent effect via increased fibrin polymerization and second to a dose-dependent effect via increased platelet sensitivity to thrombin.