PB1198 - Interference of Edoxaban in coagulation factor and inhibitor testing

Background: Assay interference through the use of direct oral anticoagulants (DOACS) is known to decrease factor activity assays and can be anticipated to increase inhibitor assays. A patient routinely using edoxaban because of atrial fibrillation developed a recurrent factor (F) VIII inhibitor which required monitoring.

Aims: To evaluate assay performance and modalities to monitor coagulation parameters in a patient with FVIII inhibitor and simultaneous edoxaban treatment.

Methods: FVIII one-stage (OSA) and chromogenic activity (CA) assays, OSA-based inhibitor assay and thrombin generation were performed. DOAC-Remove™ was applied and spiking experiments with edoxaban were performed.

Results: In this patient, large discrepancies between FVIII OSA and CA were detected up to 250% (Table 1), possibly caused by the higher dilution at which CA are performed. Indeed, further dilution of OSA resulted in increased activity levels, indicating interference in OSA. Established treatment with DOAC remove slightly increased OSA results (31.6% before; 38.5% after) but did not alter CA results. Furthermore, it decreased FVIII inhibitor titer (5.5 NBU/mL before, 4.9 NBU/mL after DOAC remove). Spiking experiments showed linear correlation between edoxaban concentration and FVIII inhibitor titer (Figure 1). In thrombin generation results, presence of inhibitor and edoxaban were represented by a decreased peak height and Area Under the Curve (15.6% and 5.2% of normalized mean of healthy individuals, respectively); the effect of DOAC remove could be observed by increase of these parameters (to 22.4% and 6.7%, respectively).

Conclusion(s): Interference of FVIII inhibitor assay by edoxaban was observed, both in the patient plasma and in spiking experiments. Interference of edoxaban and this patients’ inhibitor was observed in OSA, whereas CA appeared insensitive to both. Reduced hemostasis resulting from the acquired inhibitor and edoxaban was show by decreased thrombin generation. Use of DOAC-Remove™ and application of thrombin generation may aid in monitoring patients with an acquired factor VIII inhibitors on DOAC treatment.