Direct oral anticoagulant interference and removal in the factor VIII inhibitor assay

TL;DR

Direct oral anticoagulants can cause false-positive results in FVIII inhibitor tests, but using activated charcoal-based removal can restore test accuracy.

Contribution

Demonstrates that DOAC removal using activated charcoal effectively restores FVIII inhibitor assay reliability.

Findings

DOACs cause concentration-dependent false-positive FVIII inhibitor results.

DOAC removal with activated charcoal significantly reduces or eliminates interference.

Post-removal FVIII inhibitor values align closely with baseline concentrations.

Abstract

Direct oral anticoagulants (DOACs) interfere with clot-based assays, including factor (F)VIII testing and the Nijmegen–Bethesda assay, potentially leading to false-positive results for FVIII inhibitors. Misinterpretation of these results carries serious clinical consequences. Activated charcoal-based products, such as DOAC Remove, may restore assay accuracy, but data supporting their use in FVIII inhibitor assays are limited.

In this study, we aim to determine DOAC interference in FVIII inhibitor testing and evaluate effectivity of DOAC removal to restore assay reliability.

Normal pooled plasma was spiked with therapeutic and supratherapeutic concentrations of apixaban, edoxaban, rivaroxaban, and dabigatran. Plasma pools from persons with acquired hemophilia A were spiked with DOACs and retested with and without DOAC removal treatment to evaluate workflow performance. FVIII inhibitor activity was measured with and without activated charcoal-based DOAC removal to establish DOAC interference and removal efficacy.

Spiking experiments with DOACs caused concentration-dependent false-positive FVIII inhibitor results (>0.6 Nijmegen Bethesda Units/mL), with dabigatran showing the strongest interference and apixaban the weakest. DOAC removal substantially reduced or eliminated interference across all drugs. Post-removal FVIII inhibitor values closely matched baseline concentrations in both spiked normal pooled plasma and pooled patient plasma, with most results within ±20% of the assay variability.

DOACs significantly interfere with FVIII inhibitor assays, potentially causing clinically significant false-positive results. Activated charcoal-based DOAC removal treatment provides a practical solution to restore assay reliability. These findings support the integration of DOAC removal into anti-FVIII testing protocols for patients on anticoagulant therapy.

•DOACs may interfere with FVIII inhibitor assays.•Interference with the FVIII inhibitor assay was evaluated for 4 DOACs. The effectiveness of DOAC removal was tested.•All DOACs showed clinically relevant interference; DOAC removal treatment restored assay validity.•Accurate FVIII inhibitor assessment is feasible with the correct approach toward DOAC interference.

DOACs may interfere with FVIII inhibitor assays.

Interference with the FVIII inhibitor assay was evaluated for 4 DOACs. The effectiveness of DOAC removal was tested.

All DOACs showed clinically relevant interference; DOAC removal treatment restored assay validity.

Accurate FVIII inhibitor assessment is feasible with the correct approach toward DOAC interference.

Figures