Direct oral anticoagulants (DOACs) may cause falsely negative results of antithrombin (AT) deficiency screening.


To evaluate the impact of DOAC-Stop, an agent reversing in vitro effects of DOACs, on AT testing in anticoagulated patients.


We assessed 130 venous thromboembolism patients aged 46.7 ± 13.5 years. Blood samples were collected 2 to 27 hours after DOAC intake from 49 patients on rivaroxaban, 54 on apixaban, and 27 on dabigatran. Antithrombin activity was assessed using the activated factor X (FXa)–based and the activated factor II (FIIa)–based method twice, before and after DOAC-Stop treatment, together with plasma DOAC levels using coagulometric assays.


The use of DOAC-Stop did not influence AT activity measured using the FIIa-based assay, whereas there was a marked decrease in AT activity determined using the FXa-based assay (ΔAT = 16.9%; 95% CI, 12.9%–19.1%). The AT-FIIa assay revealed decreased AT level (<79%) in all 10 (7.7%) genetically confirmed AT-deficient patients treated with rivaroxaban or apixaban (n = 5 each), whereas the AT-FXa assay showed decreased AT activity (<83%) in 2 subjects on rivaroxaban and 1 on apixaban with low plasma DOAC concentrations (<90 ng/mL). After DOAC-Stop median AT-FXa activity lowered from 83.5% (interquartile range, 66%–143%) to 65.5% (interquartile range, 57%–75%; P = .005; ΔAT = 18%) in AT-deficient patients, without any falsely negative results. The ΔAT in the FXa-based assay correlated with rivaroxaban and apixaban concentrations in the AT-deficient patients (r = 0.99, P < .001).


Application of DOAC-Stop enables reliable evaluation of AT deficiency screening in patients taking rivaroxaban or apixaban and tested using the FXa-based method.

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Author notes

This work was supported by the Jagiellonian University Medical College (grant N41/DBS/000184 to A.U.) and by the Polish National Science Centre (grant UMO-2018/31/D/NZ5/01299 to M.Z.). The DOAC-Stop was kindly provided by Haematex Research.

Dr Undas received lecture honoraria from Bayer, Boehringer Ingelheim, and Pfizer. The other authors have no relevant financial interest in the products or companies described in this article.

Drs Ząbczyk and Natorska contributed equally.