A Diagnostic Solution for Lupus Anticoagulant Testing in Patients Taking Direct Oral FXa Inhibitors Using DOAC Filter
Open accessAbstract
Background: Direct oral factor Xa (FXa) inhibitors interfere with lupus anticoagulant (LA) assays challenging antiphospholipid syndrome diagnosis in treated patients. We evaluated a new device, called DOAC Filter, and its usefulness in this setting. It is a single-use filtration cartridge in which FXa inhibitor compounds are trapped by non-covalent binding while plasma is filtered through a solid phase. Patient samples were analyzed before and after filtration: 38 rivaroxaban, 41 apixaban, and 68 none. Anticoagulant plasma concentrations were measured using specific anti-Xa assays and HPLC-MS/MS. LA testing was performed using dilute Russell Viper Venom Time (dRVVT) and Silica Clotting Time (SCT). Baseline median [min–max] concentrations were 64.8 [17.6; 311.4] for rivaroxaban and 92.1 ng/mL [37.1; 390.7] for apixaban (HPLC-MS/MS). They were significantly correlated with anti-Xa assay results (r = 0.98 and r = 0.94, respectively). dRVVT was positive in 92% rivaroxaban and 72% apixaban and SCT in 28 and 41% of samples, respectively. Post-filtration, median % of neutralization was 100% with rivaroxaban and apixaban concentrations of, respectively, <2 [<2–2.4] and <2 ng/mL [<2–9.6] using HPLC-MS/MS. No significant effect of DOAC Filter was observed on LA testing in controls (n = 31) and LA-positive (n = 37) non-anticoagulated samples. dRVVT and SCT remained positive in, respectively, 16 and 8% of rivaroxaban and 41 and 18% of apixaban samples. DOAC Filter would be an easy-to-use device allowing FXa inhibitor removal from plasma samples, limiting their interference with LA testing in treated patients.
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Both DOAC removal strategies (absorbents and filtration) can provide incomplete drug removal or influence the clotting times, resulting in possible false positives and false negatives in LA testing.
“Both removal strategies can provide an incomplete drug removal or influence the clotting times, resulting in possible false positives and false negatives in LA testing [81,82,85,86].”
From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [86]
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EULAR recommendations for the management of antiphospholipid syndrome in adults
Tektonidou, M. G., Andreoli, L., Limper, M., Amoura, Z., Cervera, R., Costedoat-Chalumeau, N., Cuadrado, M. J., Dörner, T., Ferrer-Oliveras, R., Hambly, K., et al. (2019) · Annals of the Rheumatic Diseases · doi:10.1136/annrheumdis-2019-215213 · Cited by 1,261 · cited 1× · see citing works
“ISTH, EULAR, and BSH recommended against their use also in APS patients with a history of arterial thrombosis (8, 9).”
Update of the guidelines for lupus anticoagulant detection
PENGO, V., TRIPODI, A., REBER, G., RAND, J. H., ORTEL, T. L., GALLI, M., & DE GROOT, P. G. (2009) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2009.03555.x · Cited by 1,197 · see citing works
Tripodi, A., Cohen, H., & Devreese, K. M. J. (2020) · Journal of Thrombosis and Haemostasis · doi:10.1111/jth.14846 · Cited by 143 · cited 4× · see citing works
“While detection of solid-phase antibodies aCL and aβ2-GPI is not affected by FXa inhibitor compounds present in tested samples (13, 14), it is well-established that rivaroxaban and apixaban have the potential to compromise LA testing leading to unreliable results (false-positive/negative results) even at very low conc…”
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Research works printed but not linked: 32
- [1]Miyakis S Lockshin MD Atsumi T Branch DW Brey RL Cervera R. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. (2006) 4: 295– 306. 10.1111/j.1538-7836.2006.01753.x 16420554 · DOI · Paper page
- [2]Devreese KMJ Ortel TL Pengo V de Laat B Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibodies. Laboratory criteria for antiphospholipid syndrome: communication from the SSC of the ISTH. J Thromb Haemost JTH. (2018) 16: 809– 13. 10.1111/jth.13976 29532986 · DOI · Paper page
- [3]Garcia D Akl EA Carr R Kearon C. Antiphospholipid antibodies and the risk of recurrence after a first episode of venous thromboembolism: a systematic review. Blood. (2013) 122: 817– 24. 10.1182/blood-2013-04-496257 23760616 · DOI
- [4]Connors JM. Thrombophilia testing and venous thrombosis. N Engl J Med. (2017) 377: 1177– 87. 10.1056/NEJMra1700365 28930509 · DOI
- [5]Pengo V Denas G Zoppellaro G Jose SP Hoxha A Ruffatti A. Rivaroxaban vs warfarin in high-risk patients with antiphospholipid syndrome. Blood. (2018) 132: 1365– 71. 10.1182/blood-2018-04-848333 30002145 · DOI · Paper page
- [6]Cohen H Doré CJ Clawson S Hunt BJ Isenberg D Khamashta M. Rivaroxaban in antiphospholipid syndrome (RAPS) protocol: a prospective, randomized controlled phase II/III clinical trial of rivaroxaban versus warfarin in patients with thrombotic antiphospholipid syndrome, with or without SLE. Lupus. (2015) 24: 1087– 94. 10.1177/0961203315581207 25940537 PMC4527976 · DOI
- [7]Ruiz-Irastorza G Cuadrado MJ Ruiz-Arruza I Brey R Crowther M Derksen R. Evidence-based recommendations for the prevention and long-term management of thrombosis in antiphospholipid antibody-positive patients: report of a task force at the 13th International Congress on antiphospholipid antibodies. Lupus. (2011) 20: 206– 18. 10.1177/0961203310395803 21303837 · DOI · Paper page
- [9]Zuily S Cohen H Isenberg D Woller SC Crowther M Dufrost V. Use of direct oral anticoagulants in patients with thrombotic antiphospholipid syndrome: guidance from the scientific and standardization committee of the international society on thrombosis and haemostasis. J Thromb Haemost. (2020) 18: 2126– 37. 10.1111/jth.14935 32881337 · DOI
- [10]Arachchillage DRJ Gomez K Alikhan R Anderson JAM Lester W Laffan M. 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. Br J Haematol. (2020). 189: 212– 5. 10.1111/bjh.16308 31943138 · DOI
- [12]Konstantinides SV Meyer G Becattini C Bueno H Geersing G-J Harjola VP. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. (2020) 41: 543– 603. 10.1093/eurheartj/ehz405 31504429 · DOI
- [15]Hoxha A Mattia E Tonello M Grava C Pengo V Ruffatti A. Antiphosphatidylserine/prothrombin antibodies as biomarkers to identify severe primary antiphospholipid syndrome. Clin Chem Lab Med. (2017) 55: 890– 8. 10.1515/cclm-2016-0638 27816952 · DOI
- [16]Gay J Duchemin J Imarazene M Fontenay M Jourdi G. Lupus anticoagulant diagnosis in patients receiving direct oral FXa inhibitors at trough levels: a real-life study. Int J Lab Hematol. (2019) 41: 738– 44. 10.1111/ijlh.13101 31487115 · DOI · Paper page
- [17]Mani H Hesse C Stratmann G Lindhoff-Last E. Ex vivo effects of low-dose rivaroxaban on specific coagulation assays and coagulation factor activities in patients under real life conditions. Thromb Haemost. (2013) 109: 127– 36. 10.1160/TH12-04-0228 23138190 · DOI
- [18]Favaloro EJ Gilmore G Arunachalam S Mohammed S Baker R. Neutralising rivaroxaban induced interference in laboratory testing for lupus anticoagulant (LA): a comparative study using DOAC stop and andexanet alfa. Thromb Res. (2019) 180: 10– 9. 10.1016/j.thromres.2019.05.013 31158643 · DOI
- [19]Flieder T Weiser M Eller T Dittrich M von Bargen K Alban S. Interference of DOACs in different DRVVT assays for diagnosis of lupus anticoagulants. Thromb Res. (2018) 165: 101– 6. 10.1016/j.thromres.2018.03.009 29627719 · DOI
- [20]Ratzinger F Lang M Belik S Jilma-Stohlawetz P Schmetterer KG Haslacher H. Lupus-anticoagulant testing at NOAC trough levels. Thromb Haemost. (2016) 116: 235– 40. 10.1160/TH16-02-0081 27075441 · DOI
- [21]Bonar R Favaloro EJ Mohammed S Ahuja M Pasalic L Sioufi J. The effect of the direct factor Xa inhibitors apixaban and rivaroxaban on haemostasis tests: a comprehensive assessment using in vitro and ex vivo samples. Pathology. (2016) 48: 60– 71. 10.1016/j.pathol.2015.11.025 27020211 · DOI
- [22]Reda S Brügelmann A Müller J Oldenburg J Pötzsch B Rühl H. Functional lupus anticoagulant testing in a large retrospective cohort of thrombosis patients with direct oral anticoagulants. Sci Rep. (2020) 10: 12221. 10.1038/s41598-020-69199-1 32699227 PMC7376154 · DOI · Paper page
- [24]Exner T Michalopoulos N Pearce J Xavier R Ahuja M. Simple method for removing DOACs from plasma samples. Thromb Res. (2018) 163: 117– 22. 10.1016/j.thromres.2018.01.047 29407622 · DOI
- [25]Favresse J Lardinois B Sabor L Devalet B Vandepapeliere J Braibant M. Evaluation of the DOAC-Stop® procedure to overcome the effect of DOACs on several thrombophilia screening tests. TH Open. (2018) 2: e202– 9. 10.1055/s-0038-1657785 31249943 PMC6524876 · DOI · Paper page
- [26]Cox-Morton S MacDonald S Thomas W. A diagnostic solution for haemostasis laboratories for patients taking direct oral anticoagulants using DOAC-Remove. Br J Haematol. (2019) 187: 377– 85. 10.1111/bjh.16091 31290570 · DOI
- [27]Jourdi G Delrue M Stepanian A Valaize J Foulon-Pinto G Demagny J. Potential usefulness of activated charcoal (DOAC remove®) for dRVVT testing in patients receiving direct oral anticoagulants. Thromb Res. (2019) 184: 86– 91. 10.1016/j.thromres.2019.11.001 31710863 · DOI
- [28]Frans G Meeus P Bailleul E. Resolving DOAC interference on aPTT, PT, and lupus anticoagulant testing by the use of activated carbon. J Thromb Haemost. (2019) 17: 1354– 62. 10.1111/jth.14488 31102433 · DOI
- [29]Sevenet PO Cucini V Hervé T Depasse F Carlo A Contant G. Evaluation of DOAC Filter, a new device to remove direct oral anticoagulants from plasma samples. Int J Lab Hematol. (2020) 42: 636– 42. 10.1111/ijlh.13267 32567799 · DOI · Paper page
- [30]Keeling D Mackie I Moore GW Greer IA Greaves M British Committee for Standards in Haematology. Guidelines on the investigation and management of antiphospholipid syndrome. Br J Haematol. (2012). 157: 47– 58. 10.1111/j.1365-2141.2012.09037.x 22313321 · DOI · Paper page
- [31]van Os GMA de Laat B Kamphuisen PW Meijers JCM de Groot PG. Detection of lupus anticoagulant in the presence of rivaroxaban using Taipan snake venom time. J Thromb Haemost. (2011) 9: 1657– 9. 10.1111/j.1538-7836.2011.04395.x 21668740 · DOI
- [32]Chaturvedi S McCrae KR. Diagnosis and management of the antiphospholipid syndrome. Blood Rev. (2017) 31: 406– 17. 10.1016/j.blre.2017.07.006 28784423 PMC5714279 · DOI
- [33]Miranda S Park J Le Gal G Piran S Kherani S Rodger MA. Prevalence of confirmed antiphospholipid syndrome in 18-50 years unselected patients with first unprovoked venous thromboembolism. J Thromb Haemost. (2020) 18: 926– 30. 10.1111/jth.14720 31872492 · DOI
- [34]Platton S Hunt C. Influence of DOAC stop on coagulation assays in samples from patients on rivaroxaban or apixaban. Int J Lab Hematol. (2019) 41: 227– 33. 10.1111/ijlh.12950 30468572 · DOI · Paper page
- [35]De Kesel PM Devreese KMJ. Direct oral anticoagulant adsorption: impact on lupus anticoagulant testing-Review of the literature and evaluation on spiked and patient samples. J Thromb Haemost. (2020) 18: 2003– 17. 10.1111/jth.14894 32400112 · DOI · Paper page
- [36]Kopatz WF Brinkman HJM Meijers JCM. Use of DOAC Stop for elimination of anticoagulants in the thrombin generation assay. Thromb Res. (2018) 170: 97– 101. 10.1016/j.thromres.2018.08.014 30149286 · DOI
- [37]Merriman E Kaplan Z Butler J Malan E Gan E Tran H. Rivaroxaban and false positive lupus anticoagulant testing. Thromb Haemost. (2011) 105: 385– 6. 10.1160/TH10-08-0511 21103666 · DOI
Cited by
Sorted by citations
Lupus Anticoagulant Detection under the Magnifying Glass
Molinari, A. C., Martini, T., Banov, L., Ierardi, A., Leotta, M., Strangio, A., & Santoro, R. C. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12206654 · Cited by 9 · see citing works
“Alternatively, filtration techniques are available to remove DOACs from the plasma sample [84–86].”
BackgroundAnalytical dilemmas in lupus anticoagulant detection
Moore, G. W. (2023) · Exploration of Immunology · doi:10.37349/ei.2023.00104 · Cited by 5 · see citing works
Viewpoint: Lupus anticoagulant detection and interpretation in antiphospholipid syndrome
Efthymiou, M., Bertolaccini, M. L., & Cohen, H. (2024) · Rheumatology · doi:10.1093/rheumatology/kead623 · Cited by 5 · see citing works
- Authors
- Farkh, C., Ellouze, S., Gounelle, L., Sad Houari, M., Duchemin, J., Proulle, V., Fontenay, M., Delavenne, X., & Jourdi, G.
- Affiliations
- Hôpital Cochin (FR)
- Inserm (FR)
- Corresponding author
- Jourdi, Georges
- Venue
- Frontiers in Medicine
- Publisher
- Frontiers Media SA
- Published
- 2021-05-31
- Volume
- 8
- Pages
- 683357-683357
- ISSN
- 2296-858X (ISSN-L)
- PMC
- PMC8200390
- OpenAlex
- W3172342231
- Cited by
- 16
- References
- 3
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 3
- FWCI
- 2.64
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Surgery › Heparin-Induced Thrombocytopenia and Thrombosis
- Keywords
- lupus anticoagulant, rivaroxaban, apixaban, antiphospholipid syndrome, assay interference, plasma filtration, dilute Russell viper venom time, anti-Xa assay
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