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Licensed Unlicensed Requires Authentication Published by De Gruyter September 4, 2019

DOAC-Remove abolishes the effect of direct oral anticoagulants on activated protein C resistance testing in real-life venous thromboembolism patients

  • Magdalena Kopytek , Michał Ząbczyk ORCID logo , Krzysztof P. Malinowski , Anetta Undas and Joanna Natorska EMAIL logo

Abstract

Background

Direct oral anticoagulants (DOACs) may cause false results of activated protein C resistance (APC-R) ratio. DOAC-Remove, a new reagent based on activated carbon, has been designed to eliminate the interference of DOACs on coagulation assays. The aim of the study was to investigate whether the use of DOAC-Remove enables to determine APC-R in patients treated with DOACs.

Methods

We assessed 74 venous thromboembolism (VTE) patients, including 25 on rivaroxaban, 25 on apixaban and 24 taking dabigatran. APC-R was determined using the Russell Viper Venom Time (RVVT)-based clotting test. APC-R and DOAC concentrations were tested at baseline and following DOAC-Remove. Thrombophilia, including factor V Leiden (FVL) mutation was tested.

Results

FVL mutation was found in 20 (27%) patients. The APC-R ratio at baseline was measurable in 43 patients (58.1%), including 20 (80%) on rivaroxaban, 19 (76%) on apixaban and four (16.7%) on dabigatran. In patients with measurable APC-R at baseline, the ratio >2.9 was found in 23 patients (53.5%). In 16 (37.2%) subjects APC-R ratio <1.8 suggested FVL mutation which was genetically confirmed. Four (9.3%) FVL carriers on dabigatran showed negative/equivocal APC-R results. In 11 (14.9%) patients taking rivaroxaban or apixaban, in whom blood was collected 2–5 h since the last dose, we observed unmeasurable APC-R. DOAC-Remove almost completely eliminated all plasma DOACs. After addition of DOAC-Remove all APC-R ratios were measurable. In four FVL carriers on dabigatran with false negative APC-R, DOAC-Remove resulted in APC-R ratios <1.8.

Conclusions

DOAC-Remove effectively reduces DOACs concentration in plasma, which enables FVL testing using APC-R.


Corresponding author: Joanna Natorska, PhD, John Paul II Hospital, Kraków, Poland; and Institute of Cardiology, Jagiellonian University School of Medicine, 80 Pradnicka St, 31-202 Kraków, Poland, Phone: +48 12 614 30 04, Fax: +48 12 614 21 20

Award Identifier / Grant number: N41/DBS/ 000184

Funding statement: This work was supported by a grant from the Jagiellonian University Medical College (N41/DBS/ 000184, Funder Id: http://dx.doi.org/10.13039/100009045 to A.U.).

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Employment or leadership: None declared.

  3. Honorarium: None declared.

  4. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2019-06-27
Accepted: 2019-08-15
Published Online: 2019-09-04
Published in Print: 2020-02-25

©2020 Walter de Gruyter GmbH, Berlin/Boston

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