Influence of DOAC Stop on coagulation assays in samples from patients on rivaroxaban or apixaban

Abstract

Introduction Direct oral anticoagulants (DOACs) require no laboratory monitoring, but they interfere with almost all clotting tests to a varying degree, depending on the DOAC, assay principles and reagents used. DOAC Stop (Haematex Research, Sydney, Australia) has recently been shown to adsorb DOACs from spiked and patient plasmas. The aim of our work was to investigate the DOAC Stop effect on a range of haemostasis assays on plasmas collected from patients on rivaroxaban or apixaban, to see whether it removes the effect of these drugs to enable more accurate interpretation of coagulation assays. Methods Samples from patients anticoagulated with either rivaroxaban, apixaban or no anticoagulant were tested for prothrombin time (PT), activated partial thromboplastin time (APTT), DOAC‐specific anti‐Xa assay, factor VIII (one‐stage and chromogenic assay) and DRVVT (low and high phospholipid) before and after sample treatment with DOAC‐Stop. Results DOAC Stop significantly removed the effects of rivaroxaban and apixaban on PT, APTT, anti‐Xa activity, factor VIII (one‐stage and chromogenic assays), and DRVVT (low and high phospholipid reagents), and reduced the number of false positive of lupus anticoagulant interpretations in patients on rivaroxaban. There was no effect on the results from patients that were not anticoagulated. Conclusion This small study suggests that it is likely that DOAC Stop can be used in laboratories to screen for coagulopathy or lupus anticoagulants in samples containing rivaroxaban or apixaban. Care should be taken in the interpretation of results since complete reversal of the anti‐Xa effect did not occur in every sample.

A diagnostic solution for haemostasis laboratories for patients taking direct oral anticoagulants using DOAC‐Remove

“…adsorbs DOAC, has been investigated and found to be effective in several small laboratory studies at removing DOAC from plasma samples and allowing accurate coagulation assay testing, including LA, with the dRVVT assay (Jacquemin et al, 2015;Exner et al, 2018;Jacquemin et al, 2018;Kopatz et al, 2018;Exner et al, 2019;Platton & Hunt, 2019). In our study, APC sensitivity ratios were also significantly increased by DOAC interference (Table II), which could result in APC resistance, usually due to F5 R506Q (factor V Leiden), being missed in patients being tested on DOAC.…”

“…Several studies have investigated the use of charcoal substrate to remove DOAC from patient samples undergoing coagulation tests. DOAC Stop TM , a charcoal substrate that adsorbs DOAC, has been investigated and found to be effective in several small laboratory studies at removing DOAC from plasma samples and allowing accurate coagulation assay testing, including LA, with the dRVVT assay (Jacquemin et al , ; Exner et al , ; Jacquemin et al , ; Kopatz et al , ; Exner et al , ; Platton & Hunt, ).…”

Reducing the effect of DOAC interference in laboratory testing for factor VIII and factor IX: A comparative study using DOAC Stop and andexanet alfa to neutralize rivaroxaban effects

“…DOAC Stop has been assessed for DOAC neutralization in several studies, but mostly related to assessment of thrombophilia, 18,19,[26][27][28][29][30][31] and included in only a few studies related to factor assays. 30,32 To our knowledge, no study has previously assessed the effect of andexanet alfa on factor levels and DOAC interference. Another obvious issue to use of andexanet for in vitro reversal is cost and availability.…”

Clinical and laboratory practice for lupus anticoagulant testing: An International Society of Thrombosis and Haemostasis Scientific and Standardization Committee survey

“…The TVT/ECT has been shown to be unaffected by rivaroxaban . The use of adsorbent reagents to remove DOAC and allow LA testing in the normal way are being explored and preliminary results are encouraging …”

“…37,38 The use of adsorbent reagents to remove DOAC and allow LA testing in the normal way are being explored and preliminary results are encouraging. [39][40][41] centile is at least 300. 42,46 The poor agreement on the number of donors needed to calculate the cut-off is probably determined by the local availability and costs rather than strong views about what should be done.…”