The effect of DOAC-Stop on lupus anticoagulant testing in patients with pulmonary embolism receiving direct oral anticoagulants

Abstract

Abstract Background Direct oral anticoagulants (DOACs) are widely used as first-line treatment for pulmonary embolism (PE) but may cause false positive lupus anticoagulant (LA) based on prolongation diluted Russell's viper venom time (dRVVT) or activated partial thromboplastin time (aPTT). Exclusion of antiphospholipid syndrome is recommended in PE patients since this disease requires warfarin, not DOACs. Aims We evaluated whether the use of DOAC-Stop, an agent reversing in vitro effects of DOACs, allows for reliable LA testing in PE patients on DOACs. Methods We assessed 172 consecutive PE patients aged 48 ± 14 years (50.6 % women) screened for antiphospholipid syndrome according to ISTH guidelines. Blood was collected 1–24 h since intake of a DOAC, i.e. rivaroxaban (n=81, 47.1%), dabigatran (n=53, 30.8%) and apixaban (n=38, 22.1%). LA testing was performed after DOAC-Stop (Haematex Research, Hornsby, Australia) treatment. Positive LA was reported when the normalized (patient/standard plasma clotting time) LA screening and screening (LA1)/confirmation (LA2) ratios exceeded 1.2. Results In screening tests after DOAC-Stop use, the dRVVT remained prolonged in 9 (5.2%) patients including 4 (44.5%) on apixaban, 3 (33.3%) on rivaroxaban and 2 (22.2%) on dabigatran, while the dRVVT LA1/LA2 ratio was abnormal in 7 (4.1%) subjects: 3 (42.9%) were on apixaban, 3 (42.9%) on rivaroxaban and 1 (14.2%) on dabigatran. In 2 (22,2%) patients the dRVVT LA1/LA2 ratio exceeded 2. The aPTT-LA screening test remained prolonged in 8 (4.6%) patients including 4 (50.0%) on apixaban, 2 (25.0%) on rivaroxaban and 2 (25.0%) on dabigatran, while the aPTT LA1A/LA2A ratio was abnormal in 5 (2.9%) patients: 3 (60.0%) on apixaban, 1 (20.0%) on rivaroxaban and 1 (20.0%) on dabigatran). In 1 (12.5%) patients the aPTT LA1/LA2 ratio exceeded 2. Antiphospholipid syndrome with the presence of LA was diagnosed in 7 (87.5%) patients. False positive LA had 1 (0.6%) patients after the DOAC-Stop use. Conclusion(s) To our knowledge, this is the largest cohort of PE patients on DOACs evaluated for LA, with use of DOAC-Stop, showing reliability of such approach in the real-life setting, with <1% of patients with false positive LA.