Thrombin generation in HeartMate 3 patients on apixaban and vitamin K antagonists: Variability limits clinical applicability

Apixaban is increasingly replacing vitamin K antagonists (VKAs) during HeartMate 3 (HM3) left ventricular assist device support, but its pharmacodynamics in this setting remain poorly understood. Thrombin generation assays (TGAs) allow for comparison of the overall anticoagulant effect. TGAs were performed in 24 HM3 patients on apixaban, dosed to maintain trough levels >50 ng/liter, and 6 on VKAs with target INR 2 to 3, without recent coagulopathy. Apixaban was associated with shorter lag time and time-to-peak thrombin generation, indicating faster coagulation initiation. Endogenous thrombin potential (ETP) was higher with apixaban, but both peak thrombin and ETP showed high interindividual variability. Apixaban levels correlated modestly with initiation parameters, but not with ETP or peak thrombin. These findings demonstrate pharmacodynamic differences between apixaban and VKAs, but also highlight substantial variability and limited clinical applicability for apixaban dose titration. TGAs should therefore be regarded as research tools rather than monitoring assays in this setting.