The methods for removal of direct oral anticoagulants and heparins to improve the monitoring of hemostasis: a narrative literature review

Abstract

The assessment of hemostasis is necessary to make suitable decisions on the management of patients with thrombotic disorders. In some clinical situations, for example, during thrombophilia screening, the presence of anticoagulants in sample makes diagnosis impossible. Various elimination methods may overcome anticoagulant interference. DOAC-Stop, DOAC-Remove and DOAC Filter are available methods to remove direct oral anticoagulants in diagnostic tests, although there are still reports on their incomplete efficacy in several assays. The new antidotes for direct oral anticoagulants – idarucizumab and andexanet alfa – could be potentially useful, but have their drawbacks. The necessity to remove heparins is also arising as heparin contamination from central venous catheter or therapy with heparin disturbs the appropriate hemostasis assessment. Heparinase and polybrene are already present in commercial reagents but a fully-effective neutralizer is still a challenge for researchers, thus promising candidates remain in the research phase.

Testing for the lupus anticoagulant: the good, the bad, and the ugly

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Figure 3 Methods for neutralization of direct oral anticoagulant (DOAC) interference in coagulation assays. Source: Figures reproduced from [ 40 ]. Permission for reuse according to Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/ ).

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Simplified Method for Removing Direct Oral Anticoagulant Interference in Mechanical Coagulation Test Systems—A Proof of Concept

“…In other prothrombotic conditions, such as antiphospholipid syndrome (APS), the classical vitamin K antagonists (VKAs), including warfarin, may be preferred over DOACs [3]. Irrespective, DOACs cause interference in a wide range of hemostasis assays, especially coagulation-based assays, where they will inevitably prolong clot times [4][5][6][7][8][9][10][11]. Because of their ubiquitous presence in society, a high proportion of patients undertaking hemostasis testing will be on a DOAC when samples are collected [4][5][6][7][8][9][10][11].…”

“…Irrespective, DOACs cause interference in a wide range of hemostasis assays, especially coagulation-based assays, where they will inevitably prolong clot times [4][5][6][7][8][9][10][11]. Because of their ubiquitous presence in society, a high proportion of patients undertaking hemostasis testing will be on a DOAC when samples are collected [4][5][6][7][8][9][10][11]. In particular, a high proportion of patients being assessed for lupus anticoagulant (LA) will be on a DOAC at the time of testing [4].…”

“…The interference caused by DOACs can be effectively removed using DOAC neutralizers [4,9,10]. At the time of writing, there are three such products available commercially: DOAC Stop, DOAC Remove and DOAC Filter [4].…”

“…DOAC Stop (DS) represents the first commercial DOAC neutralizer, reported in the literature in 2018 [11], and specifically developed for this use. DS has since been found to be very useful for extracting DOACs and similar compounds from plasma samples for subsequent use in a variety of assays [4,[9][10][11][12][13][14][15][16][17][18][19][20][21][22]. DS has little or no apparent effect on clotting factors or proteins involved in the clotting mechanism [11], except perhaps for a minor reduction in tissue factor pathway inhibitor [21].…”