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FRI0593 Effects of New (Direct) Oral Anticoagulants on Lupus Anticoagulant Assays
  1. J. Antovic1,
  2. A. Antovic2,
  3. E.-M. Norberg1,
  4. M. Berndtsson1,
  5. M. Skeppholm3
  1. 1Department of Coagulation Research, Institute for Molecular Medicine & Surgery &, Karolinska Institutet & Department of Clinical Chemistry
  2. 2Dept of medicine Solna, Rheumatology Unit, Karolinska University Hospital, Rheumatology clinic, Karolinska Institutet
  3. 3Department of Medicine, Clinical Pharmacology Unit, Division of Cardiovascular Medicine, Karolinska Institutet & Danderyd Hospital, Stockholm, Sweden

Abstract

Background Laboratory diagnosis of lupus anticoagulant (LA) as a part of the diagnosis of antiphospholipid syndrome (APS) is based on prolongation of at least one coagulation assay (diluted Russel's viper venom (dRVVT) or activated partial thromboplastin time (APTT)) which normalizes after addition of phospholipids. Both assays may be influenced by anticoagulants and therefore LA should not be tested during warfarin or heparin treatment. New (direct) oral anticoagulants (N(D)OAC based on direct inhibition of thrombin (dabigatran (DAB)) or factor Xa (rivaroxaban (RIV) and apixaban (API)) are approved for the treatment of venous thromboembolism (VTE). Therefore N(D)OAC may be used in the treatment of patients with APS where LA diagnosis is critical for the decision about the VTE treatment. It has been shown (primarily in-vitro) that N(D)OAC may influence LA testing.

Objectives We have tested the effects of N(D)OAC on the assays routinely used for the diagnosis of LA in patients treated with these drugs in real life settings.

Methods Plasmas from patients with atrial fibrillation treated with DAB (n=30), RIV (n=20) and API (n=17) and known not to have LA were tested using dRVVT (LA screen and LA confirm Life Diagnostics) and APTT (PTT LA Diagnostica Stago and Actin FS Siemens Healthcare Diagnostics) assays. According to the diagnostics algorithm, the dRVVT and APTT ratio <1.2 was considered negative, >1.4 positive, while if the ratio was 1.2-1.4 LA could not be ruled out. Plasma concentrations of drugs varied between 8-172 μg/L for DAB, 8-437 μg/L for RIV and 36-178 μg/L for API.

Results Only 8 (27%) out of 30 plasmas from patients treated with DAB were negative, while 4 (13%) plasmas were positive for LA In all but 2 samples confirmation tests were also prolonged. DAB concentration correlated with both dRVVT (r=0.75 p<0.0001) and both APTT (r=0.55, p<0.005) assays, while ratio >1.2 was observed even with the lowest concentration. Negative LA was observed only in one sample from the patients treated with RIV (drug concentration 8 μg/L), while half of the samples diagnosed positive for LA. Confirmation tests were prolonged with RIV concentration above 100 μg/l. RIV concentration correlated with both dRVVT assays (r=0.86 p<0.0001) and both dRVVT and APTT ratio (r=0.56, p=0.01). LA diagnosed positive in 7 (41%) samples from patients treated with API. Eight samples (47%) were diagnosed negative for the presence of LA. Correlation between API concentration and dRVVT confirm test was observed (r=0.83, p<0.001) and it seems that a concentration >100 μg/L was associated with the prolongation of this confirmatory assay.

Conclusions Our results suggest that the risk of overestimation of LA detection is present in samples from patients treated with N(D)OAC, particularly RIV. Therefore LA testing should not be performed in patients during the treatment with N(D)OAC. Prolongation of confirmation assays may be helpful for the recognition of false positivity, especially in the case of DAB.

Disclosure of Interest None declared

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