How the Direct Oral Anticoagulant Apixaban Affects Thrombin Generation Parameters

•The anticoagulant effect of apixaban was evaluated in plasmas spiked with the drug.•Apixaban has little effect on PT or APTT•Apixaban does affect all the parameters of thrombin generation•Lag-time (increased); ETP, thrombin-peak and velocity index (decreased).•The effects were more pronounced in the presence of thrombomodulin.

Background and objectivesApixaban is a direct oral anticoagulant (DOAC) targeting factor Xa and thus quenching thrombin generation and clot formation. However, little information is available on the influence that apixaban may have on the parameters of thrombin generation.MethodsAliquots of a pooled normal plasma have been added with increased concentrations of purified apixaban and were used to assess the degree of modification brought about by the drug on the basic tests of coagulation prothrombin and activated partial thromboplastin time (PT and APTT) and on thrombin generation parameters.ResultsThe study shows that while apixaban has little effect on PT or APTT it does affect all the parameters of thrombin generation, including the lag-time (which is increased), the endogenous thrombin potential (ETP) and thrombin-peak (both decreased although to a different extent), and the velocity index (decreased). Interestingly, the above effects were more pronounced when the measurements were recorded in the presence of thrombomodulin, thus making the ratio (with/without thrombomodulin) to decrease consistently as a function of the apixaban concentrations.ConclusionsThese findings support the antithrombotic properties of apixaban and can help to understand the mechanism(s) of action of this drug. Thrombin generation could be used as a convenient laboratory tool to assess the anticoagulant activity of other drugs and to make between-DOAC comparison.