Influence of DOACS and DOAC-REMOVE® on coagulation assays during thrombophilia testing in DOAC-treated patients

Abstract

Background/Aim. Direct oral anticoagulants (DOACs) administration significantly interferes with coagulation as-says. The aim of the study was to evaluate the effect of DOACs and DOAC-Remove® on coagulation assays dur-ing thrombophilia testing. Methods. The study was car-ried out from January 2019 to the end of June 2020. It in-cluded 30 DOAC-treated patients, 14 females and 16 males aged 23 to 63 (median age 47.6 years), tested for thrombophilia due to venous thromboembolism (VTE). Thrombophilia testing was performed using DOAC-Remove® tablets (activated charcoal). The results before and after DOAC-Remove® were compared. Results. Posi-tive lupus anticoagulant (LA) results were observed in 20% apixaban, 100% dabigatran, and 70% rivaroxaban-treated patients, while in samples after DOAC-Remove®, the LA positivity was observed only in one from the apix-aban group. Before DOAC-Remove®, the activated pro-tein C (APC) resistance (APC-R) was measurable in 40% dabigatran and 80% rivaroxaban-treated patients, while, after using DOAC-Remove®, the APC-R was measurable in all cases. Comparing the results obtained from the sam-ples before and after DOAC-Remove®, a difference was noted in relation to all dilute Russell's viper venom time (dRVVT) coagulation tests, except for the dRVVT ratio in the apixaban group. Clot-based methods for detecting the APC resistance were significantly affected by dabigatran and less by rivaroxaban. Conclusion. DOACs were prac-tically inactivated after the addition of the DOAC-Remove®, which made it possible to perform analyses for the LA and APC-R testing freely and obtain relevant re-sults.

Uvod/Cilj. Primena direktnih oralnih antikoagulansa (DOAK) značajno utiče na testove koagulacije. Cilj rada bio je da se pro- ceni uticaj DOAK i DOAC-Remove® tableta (aktivni ugalj) na testove koagulacije tokom ispitivanja trombofilije. Metode. Istraživanjem, sprovedenim od januara 2019. do juna 2020. godine, obuhvaćeno je 30 bolesnika lečenih DOAK-om i testiranih na trombofiliju zbog venskog tromboembolzma (VTE). Bilo je 14 žena i 16 muškaraca, starosti od 23 do 63 godine (medijana 47,6 godina). Ispitivanje trombofilije izvršeno je upotrebom DOAC-Remove® tableta (aktivni ugalj). Upoređivani su rezultati pre i posle primene DOAC-Remove®. Rezultati. Pozitivni rezultati za lupus antikoagulantni (LA) test dobijeni su kod 20% bolesnika lečenih apiksabanom, kod 100% bolesnika lečenih dabigatranom i kod 70% lečenih riva- roksabanom, a u uzorcima posle DOAC-Remove® pozitivnost na LA dobijena je samo kod jednog bolesnika iz grupe lečnih apiksabanom. Pre primene DOAC-Remove®, rezistencija na aktivisani protein C (activated protein C resistance – APC-R) bila je merljiva kod 40% i 80% bolesnika lečenih dabigatranom, od- nosno rivaroksabanom, dok je posle primene DOAC- Remove®, APC-R bila merljiva u svim slučajevima. Upoređivanjem rezultata dobijenih iz uzoraka pre i posle primene DOAC-Remove®, primećena je razlika u odnosu na sve testove vremena koagulacije izvršene razblaženim Russell- ovim zmijskim otrovom (dilute Russell’s viper venom time – dRVVT), osim dRVVT u grupi bolesnika lečenih apiksabanom. Na koagulacionu metodu za otkrivanje APC-R značajno je uti- cao dabigatran, a manje rivaroksaban. Zaključak. Nakon primene DOAC-Remove® tableta, DOAK su praktično inaktivisani što je omogućilo izvođenje analiza za LA i APC-R i dobijanje relevantnih rezultata testova.