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Cited by 14Systemic Lupus Erythematosus ResearchBlood Coagulation and Thrombosis MechanismsVenous Thromboembolism Diagnosis and Management

Functional Lupus Anticoagulant Testing in a Large Retrospective Cohort of Thrombosis Patients with Direct Oral Anticoagulants

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Reda, Sara, Brügelmann, Anna, Müller, Jens, Oldenburg, Johannes, Pötzsch, Bernd, Rühl, Heiko·2020·Scientific Reports
DOI 10.1038/s41598-020-69199-1PMC PMC7376154
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Abstract

Abstract Functional tests for lupus anticoagulants (LA) as part of a thrombophilia workup are commonly performed in patients under anticoagulant therapy that may interfere with assay results. There is no consensus on how these tests should be assessed in patients on direct oral anticoagulants (DOACs). In this retrospective cohort study, we analysed data from patients with a history of thrombosis in whom dilute Russell viper venom time (dRVVT), LA-sensitive aPTT, and solid phase assays for antiphospholipid antibodies (aPL) were performed (n = 3,147, thereof 588 on rivaroxaban, 144 on apixaban, 1,179 on other anticoagulant drugs). The dRVVT ratio was correlated with rivaroxaban (r = 0.30, P < 10–4) but not with apixaban plasma levels. The LA-sensitive aPTT/aPTT ratio showed no correlation with DOAC levels. Correspondingly, the rate of patients with abnormal dRVVT test was significantly higher (P < 10–4) under rivaroxaban (88%) than in thrombosis patients without anticoagulant medication (6%), independent from their aPL plasma levels. No isolated positive results of functional LA testing in patients on anticoagulants could be confirmed in repeated testing after discontinuation of the medication (n = 40). These data indicate that rivaroxaban should be discontinued before functional LA testing is performed. However, viable interpretation of these tests appears to be less affected in patients on apixaban.

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  • All DOACs prolong dRVVT in screening and confirmatory procedures, with rivaroxaban affecting screening more than confirmatory (increasing potential false positives) and opposite apixaban action (increasing potential false negatives).

    “all DOACs prolong dRVVT in screening and confirmatory procedures, with rivaroxaban affecting screening more than confirmatory (increasing potential false positives) and opposite apixaban action (increasing potential false negatives) [73,74,75,76,77,78].”

    From Lupus Anticoagulant Detection under the Magnifying Glass (2023) · cites this paper as [74]

    The Results (Effect of anticoagulant drugs on functional LA testing; page unavailable) report that rivaroxaban levels correlate with both dRVVT screening and confirmatory tests and with an increased dRVVT ratio, supporting the concern about false positives. They do not establish that all DOACs prolong both tests: the study evaluated rivaroxaban and apixaban, and found no significant correlation between apixaban levels and the dRVVT ratio. The claimed opposite effect of apixaban and increased potential for false negatives are not supported by these passages. (LLM, conf=0.88)

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Research works printed but not linked: 25

  1. [1]Chaturvedi S McCrae KR Diagnosis and management of the antiphospholipid syndrome Blood Rev. 2017 31 406 417 10.1016/j.blre.2017.07.006 28784423 PMC5714279 · DOI
  2. [2]Andreoli L Estimated frequency of antiphospholipid antibodies in patients with pregnancy morbidity, stroke, myocardial infarction, and deep vein thrombosis: A critical review of the literature Arthritis Care Res. 2013 65 1869 1873 10.1002/acr.22066 23861221 · DOI
  3. [3]Connors JM Thrombophilia testing and venous thrombosis N. Engl. J. Med. 2017 377 1177 1187 10.1056/NEJMra1700365 28930509 · DOI
  4. [4]Miyakis S 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
  5. [5]Wilson WA International consensus statement on preliminary classification criteria for definite antiphospholipid syndrome: Report of an international workshop Arthritis Rheum. 1999 42 1309 1311 10.1002/1529-0131(199907)42:7<1309::AID-ANR1>3.0.CO;2-F 10403256 · DOI
  6. [8]Galli M Antiphospholipid syndrome: Association between laboratory tests and clinical practice Pathophysiol. Haemost. Thromb. 2003 33 249 255 10.1159/000083810 15692225 · DOI
  7. [9]Ruffatti A Antibody profile and clinical course in primary antiphospholipid syndrome with pregnancy morbidity Thromb. Haemost. 2006 96 337 341 10.1160/TH06-05-0287 16953276 · DOI · Paper page
  8. [10]Galli M Barbui T Antiphospholipid antibodies and thrombosis: Strength of association Hematol. J. 2003 4 180 186 10.1038/sj.thj.6200206 12764350 · DOI
  9. [13]Keeling D 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
  10. [14]Merriman E Rivaroxaban and false positive lupus anticoagulant testing Thromb. Haemost. 2011 105 385 386 10.1160/TH10-08-0511 21103666 · DOI
  11. [15]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 109 127 136 10.1160/TH12-04-0228 23138190 · DOI
  12. [16]van Os GM de Laat B Kamphuisen PW Meijers JC de Groot PG Detection of lupus anticoagulant in the presence of rivaroxaban using Taipan snake venom time J. Thromb. Haemost. 2011 9 1657 1659 10.1111/j.1538-7836.2011.04395.x 21668740 · DOI
  13. [17]Bonar R 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
  14. [18]Bonar R The effect of dabigatran on haemostasis tests: A comprehensive assessment using in vitro and ex vivo samples Pathology 2015 47 355 364 10.1097/PAT.0000000000000252 25938348 · DOI
  15. [19]Góralczyk T Iwaniec T Wypasek E Undas A False-positive lupus anticoagulant in patients receiving rivaroxaban: 24 h since the last dose are needed to exclude antiphospholipid syndrome Blood Coagul. Fibrinolysis 2015 13 1264 1273 25402189
  16. [20]Martinuzzo ME 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 10.1111/ijlh.12138 24034808 · DOI · Paper page
  17. [21]Arachchillage DR Interactions between rivaroxaban and antiphospholipid antibodies in thrombotic antiphospholipid syndrome J. Thromb. Haemost. 2015 13 1264 1273 10.1111/jth.12917 25850997 · DOI
  18. [22]Hillarp A Effects of the oral, direct factor Xa inhibitor edoxaban on routine coagulation assays, lupus anticoagulant and anti-Xa assays Scand. J. Clin. Lab. Investig. 2018 78 575 583 10.1080/00365513.2018.1522664 30278787 · DOI
  19. [23]Hillarp A Effects of the oral, direct factor Xa inhibitor apixaban on routine coagulation assays and anti-FXa assays J. Thromb. Haemost. 2014 12 1545 1553 10.1111/jth.12649 24965851 · DOI
  20. [24]Douxfils J Laboratory testing in patients treated with direct oral anticoagulants: A practical guide for clinicians J. Thromb. Haemost. 2018 16 209 219 10.1111/jth.13912 29193737 · DOI
  21. [25]Murer LM Pirruccello SJ Koepsell SA Rivaroxaban therapy, false-positive lupus anticoagulant screening results, and confirmatory assay results Lab. Med. 2016 47 275 278 10.1093/labmed/lmw029 27474775 · DOI
  22. [26]Ratzinger F Lupus-anticoagulant testing at NOAC trough levels Thromb. Haemost. 2016 116 235 240 10.1160/TH16-02-0081 27075441 · DOI
  23. [27]Antovic A Effects of direct oral anticoagulants on lupus anticoagulant assays in a real-life setting Thromb. Haemost. 2017 117 1700 1704 10.1160/TH17-03-0204 28640321 · DOI · Paper page
  24. [28]Kim PY Mechanistic basis for the differential effects of rivaroxaban and apixaban on global tests of coagulation T. H. Open 2018 2 e190 e201 10.1055/s-0038-1649507 PMC6524873 31249942 · DOI
  25. [29]Triplett DA Brandt J Laboratory identification of the lupus anticoagulant Br. J. Haematol. 1989 73 139 142 10.1111/j.1365-2141.1989.tb00242.x 2510814 · DOI

Cited by

Sorted by citations

Authors
Reda, S., Brügelmann, A., Müller, J., Oldenburg, J., Pötzsch, B., & Rühl, H.
Affiliations
University of Bonn (DE)
Corresponding author
Rühl, Heiko
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2020-07-22
Volume
10
Issue
1
Pages
12221-12221
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-020-69199-1
PMC
PMC7376154
OpenAlex
W3044781640
Cited by
14
References
4
Citations by year
2026: 4 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 4 · 2021: 1
FWCI
1.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Rheumatology › Systemic Lupus Erythematosus Research
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
  • Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
Keywords
lupus anticoagulant, direct oral anticoagulants, rivaroxaban, apixaban, dilute Russell viper venom time, antiphospholipid antibodies, thrombosis, anticoagulant interference, assay interference, anticoagulation discontinuation
MeSH terms
Rivaroxaban, Dabigatran, Administration, Oral, Adult, Anticoagulants, Blood Coagulation, Blood Coagulation Tests, Female, Humans, Male, Middle Aged, Partial Thromboplastin Time, Prothrombin Time, Pyrazoles, Pyridones, Retrospective Studies, Thrombosis, Lupus Coagulation Inhibitor, Antiphospholipid Syndrome, Antibodies, Antiphospholipid, Thrombophilia

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