The effect of DOAC-Stop on lupus anticoagulant testing in plasma samples of venous thromboembolism patients receiving direct oral anticoagulants

Abstract

Background Direct oral anticoagulants (DOACs) cause false positive lupus anticoagulant (LA) results. We assessed the impact of DOAC-Stop, reversing in vitro effects of DOACs, on LA testing in anticoagulated patients. Methods We assessed 75 venous thromboembolism patients aged 44.5±14.6 years. Blood samples were collected 2–28 h since intake of DOACs, including 50 patients on rivaroxaban, 20 on dabigatran and five on apixaban. LA testing was performed at baseline and after DOAC-Stop treatment. Positive LA was defined as the normalized (patient/standard plasma clotting time) LA screening and screening (LA1)/confirmation (LA2) ratios exceeding 1.2. Results LA diluted Russell’s viper venom time (dRVVT) normalized screening test revealed abnormal results in 73 (97.3%) and activated partial thromboplastin time (APTT)-LA in 49 (65.3%) patients. In six (8%) patients, antiphospholipid syndrome (APS) was diagnosed. dRVVT LA1/LA2 was abnormal in 35 (50.7%) patients taking DOACs. The APTT ratio was normal in all studied subjects. DOAC-Stop completely removed dabigatran and reduced by 98% rivaroxaban and by 92.3% apixaban concentrations (all p<0.05). After DOAC-Stop screening dRVVT remained prolonged in 34 (49.3%) patients (p<0.001), while dRVVT LA1/LA2 was abnormal in six (8.7%) subjects, with no association with DOAC concentrations at baseline and after DOAC-Stop. The APTT-LA screening test remained prolonged in five (7.2%) patients, while the APTT LA1/LA2 ratio was normal in those subjects. DOAC-Stop did not influence LA testing in APS patients. Conclusions Application of DOAC-Stop effectively reduced plasma DOAC concentrations leading to appropriate dRVVT results in up to 97% of VTE patients.

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

“…There were relatively small numbers of patients in the validation of DOAC‐Remove; however, this is likely to reflect real world experience of reference laboratories. In addition, as already described, there are other studies which have validated another charcoal DOAC neutraliser (DOAC Stop) (Kopatz et al , ; Zabczyk et al , ). Our study did not incorporate warfarin into the algorithm, however we believe this is probably not problematic.…”

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.…”

Addendum to British Society for Haematology Guidelines on Investigation and Management of Antiphospholipid syndrome, 2012 (Br. J. Haematol. 2012; 157: 47–58): use of direct acting oral anticoagulants

“…No alternatives exist for LA detection in samples containing direct thrombin inhibitors. Some studies have suggested that absorption methods to remove the DOACs are effective (Exner et al ., ; Cox‐Morton et al ., ; Platton & Hunt, ; Zabczyk et al ., ) but none of these methods are validated in a large number of samples from true positive and negative patients with APS.…”