Use of DOAC Stop for elimination of anticoagulants in the thrombin generation assay

Calibrated automated thrombography (CAT) is useful in monitoring the anticoagulant status of patients treated with direct oral anticoagulants (DOACs). This as well as other applications of the CAT are hampered by the wide inter-individual variation, making the diagnosis of the anticoagulant status of a patient on DOAC difficult when using normal pooled plasma as a reference. With dabigatran, the CAT is further hampered, as this direct thrombin inhibitor also inhibits the calibrator that is used in CAT. In this study we examined the added value of the universal DOAC adsorbent DOAC Stop in CAT. For this, we used normal pooled plasma spiked with apixaban, dabigatran, edoxaban or rivaroxaban, and performed CAT with 5 pM tissue factor. DOAC Stop effectively removed DOACs from plasma, leaving the DOAC Stop-treated plasma slightly more procoagulant compared to sham treated, non-anticoagulated plasma. Examining levels of natural coagulation inhibitors revealed a slight reduction in tissue factor pathway inhibitor upon DOAC Stop treatment. When DOAC Stop-treated plasma was used in the calibrator wells, normal unaffected calibration curves were observed, even when dabigatran was present. In conclusion, DOAC Stop can be used to abolish dabigatran influences of anticoagulated plasma when used in the calibrator wells. Also, the anticoagulant status of a DOAC treated patient can be diagnosed simply by comparing untreated plasma with the same plasma sample treated with DOAC Stop. Using this approach, a minor DOAC-independent increase in CAT response in the DOAC Stop-treated sample should be taken into account.