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

Clin Chem Lab Med. 2019 Aug 27;57(9):1374-1381. doi: 10.1515/cclm-2018-1197.

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.

Keywords: DOAC-Stop; antiphospholipid syndrome testing; direct oral anticoagulants (DOAC); lupus anticoagulant.

MeSH terms

  • Administration, Oral
  • Adult
  • Anticoagulants / pharmacology
  • Antiphospholipid Syndrome / diagnosis
  • Blood Coagulation / drug effects
  • Blood Coagulation Tests / methods
  • Dabigatran / pharmacology
  • Factor Xa Inhibitors / chemistry
  • Factor Xa Inhibitors / metabolism*
  • Factor Xa Inhibitors / pharmacology
  • False Positive Reactions
  • Female
  • Humans
  • Lupus Coagulation Inhibitor / analysis
  • Lupus Coagulation Inhibitor / blood
  • Lupus Coagulation Inhibitor / drug effects*
  • Male
  • Middle Aged
  • Partial Thromboplastin Time
  • Plasma / metabolism
  • Prothrombin Time
  • Pyrazoles
  • Pyridones
  • Rivaroxaban / pharmacology
  • Venous Thromboembolism / drug therapy
  • Venous Thromboembolism / metabolism

Substances

  • Anticoagulants
  • Factor Xa Inhibitors
  • Lupus Coagulation Inhibitor
  • Pyrazoles
  • Pyridones
  • apixaban
  • Rivaroxaban
  • Dabigatran