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

ABSTRACT

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.