Background Monitoring of anticoagulant activity of direct oral anticoagulants (DOACs) can be necessary in special situations. DOAC plasma levels have a high inter‐ and intraindividual variation and do not necessarily reflect the coagulation status of the patient. Thrombin generation (TG) is a global hemostatic assay with the capacity to overcome this limitation. The aim of this study was to show correlations between DOAC plasma levels and TG parameters using the fully automated ST Genesia system. Methods A total of 380 blood samples (120 with apixaban, 79 with dabigatran, 79 with edoxaban, and 102 with rivaroxaban) from patients at different time points after DOAC intake were included in the analysis. DOAC plasma levels were analyzed using calibrated anti‐Xa or anti‐IIa tests. Thrombin generation was measured using the ST Genesia system and STG‐DrugScreen reagent. Results There was a significant correlation between the drug levels of all DOACs and the TG parameters’ lag time and time to peak. Peak thrombin and velocity index show a negative correlation following an exponential regression curve with all anti‐Xa DOACs but not with dabigatran. Apart from a weak correlation with rivaroxaban, there was no correlation between drug levels of all other DOACs and endogenous thrombin potential. Conclusion TG parameters measured with ST Genesia correlate with the drug levels of anti‐Xa DOACs. Peak thrombin and velocity index are of special interest for the determination of residual anticoagulant effect at low drug levels. For dabigatran‐treated patients, only lag time shows a correlation with the dabigatran plasma levels.

Background The antithrombotic effect of direct oral anticoagulants (DOAC) in specific clinical scenarios is difficult to assess. Objective This study aimed to evaluate the effect of DOAC on thrombin generation (TG) in relation to their plasma level. Methods Eighty patients newly started on anticoagulation were included, 20 patients for each DOAC—apixaban, edoxaban, rivaroxaban, and dabigatran. Plasma was sampled before DOAC (baseline), at plasma peak time, 6 and 12 hours after starting DOAC for quantification of drug levels and TG. Results The baseline TG before DOAC intake showed inter‐individual variability. All DOACs significantly prolonged lag time (LT) and time to peak (TTP), but did not change endogenous thrombin potential (ETP). Anti‐Xa inhibitors but not dabigatran reduced thrombin peak, but the effect of apixaban at plasma peak was less pronounced (factor 1.6). LT and TTP prolongation of dabigatran was lower compared to anti‐Xa inhibitors. All DOACs showed a nonlinear dose‐response relationship, with the greatest antithrombotic effect at lower DOAC plasma levels. The inhibition of TG parameters between baseline and peak was parallel between individual patients but the coefficient of variation of TG was lower compared to drug levels. Conclusion The antithrombotic effect at DOAC peak plasma level measured by TG depends on the patient‐specific baseline TG level and the drug‐specific inhibition by the particular DOAC. Although peak plasma levels have a high variability, the variation of TG is lower compared to drug levels. Therefore, TG assays may be superior to plasma levels in the assessment of the intensity of anticoagulation.

Background The residual antithrombotic activity 12 hours after intake of direct oral anticoagulants (DOACs) is of clinical relevance in the setting of bleeding or urgent surgery. Objective To evaluate the effects of DOACs on thrombin generation 12 hours after DOAC intake in comparison to baseline and a healthy control group. Methods Eighty patients were recruited, 20 patients for each approved DOAC: apixaban, edoxaban, rivaroxaban, and dabigatran. The patients were either to be put on anticoagulation for the first time or had stopped taking oral anticoagulation for at least 48 hours. Blood plasma was sampled before (baseline) and 12 hours after starting DOAC for quantification of drug levels and thrombin generation assayed using an automated system (ST Genesia). Sixty‐one blood donors served as control group. Results The factor Xa inhibitors significantly increased lag time (137%‐219%) and reduced thrombin peak (47%‐76%) and velocity index (17%‐44%) after 12 hours compared to baseline. Dabigatran showed prolongation of lag time to 133% and time to peak to 119%. All patients had residual antithrombotic activity, with reduced thrombin generation parameters 12 hours after DOAC intake compared to baseline and to the healthy control group. This effect remained significant in patients with low residual DOAC plasma levels <50 ng/mL. Conclusion Thrombin generation remains reduced 12 hours after DOAC intake. While thrombin peak is particularly modified by factor Xa inhibitors, all DOACs prolong the lag time and time to thrombin peak. In the setting of bleeding or urgent surgery, the automated thrombin generation assay may assist in decision making and antidote administration.

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