RSS-Feed abonnieren
DOI: 10.1160/TH17-03-0204
Effects of direct oral anticoagulants on lupus anticoagulant assays in a real-life setting
Publikationsverlauf
Received:
26. März 2017
Accepted after minor revision:
13. Mai 2017
Publikationsdatum:
08. November 2017 (online)
![](https://www.thieme-connect.de/media/10.1055-s-00035024/201709/lookinside/thumbnails/10-1160-th17-03-0204-1.jpg)
Summary
Laboratory diagnosis of lupus anticoagulant (LA) is based on prolongation in at least one coagulation assay (diluted Russell’s viper venom time – dRVVT or activated partial thromboplastin time – aPTT), which normalises after addition of phospholipids. Both assays may be influenced by anticoagulants and therefore LA should not be tested during warfarin or heparin treatment. It has been shown (primarily in vitro) that direct oral anticoagulants (DOACs – dabigatran [DAB], rivaroxaban [RIV] and apixaban [API]) may also influence LA testing. We tested the effects of DOACs on assays routinely used for the diagnosis of LA in patients treated with these drugs in a real-life setting. Plasma from patients with atrial fibrillation treated with DAB (n=30), RIV (n=20) and API (n=17) and not known to have LA were tested using dRVVT (LA-screen and LA-confirm, Life Diagnostics) and aPTT (PTT-LA, Diagnostica Stago and aPTT Actin FS, Siemens Healthcare Diagnostics) assays. According to the diagnostics algorithm, dRVVT and aPTT ratios of <1.2 were considered negative, ratios of >1.4 positive, while if the ratios were 1.2–1.4 LA could not be ruled out. Plasma concentrations varied between 8–172 µg/l for DAB, 8–437 µg/l for RIV and 36–178 µg/l for API. LA diagnosis was negative in only eight (27 %) plasma samples from patients treated with DAB, and in five (25 %) and four samples (24 %) from patients treated with RIV and API, respectively. LA Positivity (dRVVT and aPTT ratios >1.4) was found in 5 cases (17 %) among patients treated with DAB, in 10 cases (50 %) treated with RIV and in 7 cases (41 %) treated with API. A concentration-dependent effect of DOACs on dRVVT-based parameters was observed, particularly as regards DAB. At lower concentrations, RIV and API had only minor effects on the confirmatory tests (below 100 µg/l and 70 µg/l, respectively). Our results suggest that a risk of overestimation of LA detection is present in samples from patients treated with DOACs. Therefore, LA testing should not be performed during treatment with DOACs. Prolongation in confirmatory assays may be helpful for the recognition of false positivity, especially as regards DAB.
-
References
- 1 Miyakis S, Lockshin MD, Atsumi D. et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 04: 295-306.
- 2 Favaloro EJ, Wong RC, Silvestrini R. et al. A multilaboratory peer assessment quality assurance program-based evaluation of anticardiolipin antibody, and beta2-glycoprotein I antibody testing. Semin Thromb Hemost 2005; 31: 73-84.
- 3 Pengo V, Tripodi A, Reber G. et al. Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. Update of the guidelines for lupus anticoagulant detection. J Thromb Haemost 2009; 07: 1737-1740.
- 4 Tripodi A, de Laat B, Wahl D. et al. for the Subcommittees on Control of Anti-coagulation and Lupus Anticoagulant/Antiphospholipid Antibodies. Monitoring patients with the lupus anticoagulant while treated with vitamin K antagonists: communication from the SSC of the ISTH. J Thromb Haemost 2016; 14: 2304-2307.
- 5 Baglin T. Clinical use of new oral anticoagulant drugs: dabigatran and rivaroxaban. Br J Haematol 2013; 163: 160-167.
- 6 Moore GW. Recent guidelines and recommendations for laboratory detection of lupus anticoagulants. Semin Thromb Hemost 2014; 40: 163-171.
- 7 Halbmayer WM, Weigel G, Quehenberger P. et al. Interference of the new oral anticoagulant dabigatran with frequently used coagulation tests. Clin Chem Lab Med 2012; 50: 1601-1605.
- 8 Douxfils J, Mullier F, Robert S. et al. Impact of dabigatran on a large panel of routine or specific coagulation assays. Laboratory recommendations for monitoring of dabigatran etexilate. Thromb Haemost 2012; 107: 985-997.
- 9 Samama MM, Martinoli JL, LeFlem L. et al. Assessment of laboratory assays to measure rivaroxaban - an oral, direct factor Xa inhibitor. Thromb Haemost 2010; 103: 815-825.
- 10 Merriman E, Kaplan Z, Butler J. et al. Rivaroxaban and false positive lupus anticoagulant testing. Thromb Haemost 2011; 105: 385-386.
- 11 Martinuzzo ME, Barrera LH, Dàdamo MA. et al. Frequent false-positive results of lupus anticoagulant tests in plasmas of patients receiving the new oral anticoagulants and enoxaparin. Int J Lab Hematol 2014; 36: 144-150.
- 12 Ratzinger F, Lang M, Belik S. et al. Lupus-anticoagulant testing at NOAC trough levels. Thromb Haemost 2016; 116: 235-240.
- 13 Lippi G, Favaloro EJ. Recent guidelines and recommendations for laboratory assessment of the direct oral anticoagulants (DOACs): is there a consensus?. Clin-Chem Lab Med 2015; 53: 185-197.
- 14 van Os GM, de Laat B, Kamphuisen PW. et al. Detection of lupus anticoagulant in the presence of rivaroxaban using Taipan snake venom time. J Thromb Haemost 2011; 09: 1657-1659.
- 15 Triplett DA, Stocker KF, Unger GA. et al. The Textarin/Ecarin ratio: a confirmatory test for lupus anticoagulants. Throm Haemost 1993; 70: 925-931.
- 16 Hillarp A, Gustafsson KM, Faxalv L. et al. Effects of the oral, direct factor Xa inhibitor apixaban on routine coagulation assays and anti-FXa assays. J Thromb Haemost 2014; 12: 1545-1553.