Effect of apixaban on common coagulation analyses

Inger Fagerberg Blixter1,* and coagulation advisory board at the External Quality Assurance in Laboratory Medicine in Sweden (Equalis)

1Koagulationslaboratoriet, Sahlgrenska Universitetssjukhuset, Gothenburg, Sweden

Introduction: Apixaban is an oral direct factor Xa inhibitor developed for prophylaxis and treatment of thromboembolic disorders. Laboratory monitoring is not necessary but the dose dependent effects on common coagulation reagents and assay procedures are far from well-known.

Objectives: To investigate the effect of apixaban on commonly used coagulation assays and evaluate anti-Xa assays for specific determination of the drug concentration in plasma.

Methods: Apixaban was added to plasma from ten healthy subjects in the concentration range 0 -1000 µg/L and analyzed using different reagents for activated partial thromboplastin time (APTT), prothrombin time (PT), antithrombin, protein C, protein S assays and anti-Xa assays.

Results: At an expected therapeutic peak concentration of apixaban, the effect on the different APTTs and PTs were weak. The concentration needed to double the APTT varied between 2200 to 4700 µg/L and between 700 and 3900 µg/L for the different PT reagents. The results from antithrombin, protein C and protein S assays were strongly dependent on the type of reagent. Chromogenic anti-Xa assays can be calibrated with apixaban and used for specific determination of the drug in plasma.

Conclusion: Different assays, and even different reagents within an assay group, display variable effects by therapeutic concentrations of apixaban but the effects were much smaller compared to rivaroxaban, another novel Xa-inhibitor. In general, coagulation based assays are unreliable to use concomitant with apixaban therapy. Furthermore, the use of APTT and/or PT assays, as screening of the anticoagulant activity of apixaban cannot be recommended. Chromogenic anti-Xa assay can be deployed for reliable measurements of apixaban concentration in plasma.

Keywords: Blood