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Semin Thromb Hemost 2024; 50(08): 1103-1113
DOI: 10.1055/s-0043-1776406
Review Article

Variable Performance of Lupus Anticoagulant Testing: The Australasian/Asia-Pacific Experience

Emmanuel J. Favaloro 
1   Department of Haematology, Sydney Centres for Thrombosis and Haemostasis, Institute of Clinical Pathology and Medical Research (ICPMR), NSW Health Pathology, Westmead Hospital, Westmead, NSW, Australia
2   Faculty of Science and Health, Charles Sturt University, Wagga Wagga, NSW, Australia
3   School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Westmead Hospital, Westmead, New South Wales, Australia
,
Elysse Dean
4   RCPA QAP Haematology, St Leonards, NSW, Australia
,
Sandya Arunachalam
4   RCPA QAP Haematology, St Leonards, NSW, Australia
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Abstract

Lupus anticoagulant (LA) is one of three tests identified as laboratory criteria for definite antiphospholipid syndrome (APS). The other two tests are anticardiolipin antibody (aCL) and anti-β2-glycoprotein I (aβ2GPI) antibody. The presence of LA is assessed using clot-based tests, while the presence of aCL and aβ2GPI is assessed by immunological assays. Since no test can be considered 100% sensitive or specific for LA, current guidelines recommend using two different clot-based assays reflecting different principles, with the dilute Russell viper venom time (dRVVT) and activated partial thromboplastin time (aPTT) recommended. Initially, LA-sensitive reagents are used to screen for LA, and then, in “screen-positive” samples, LA-“insensitive” reagents are used to confirm LA. Because LA assays are based on clot detection, anything that can interfere with fibrin clot development may affect test results. In particular, in addition to LA, the tests are also sensitive to the presence of a wide range of clinical anticoagulants, reflecting preanalytical issues for testing. We provide updated findings for LA testing in our geographic region, using recent data from the Royal College of Pathologists of Australasia Quality Assurance Programs, an international external quality assessment program with approximately 120 participants. Data show a wide variety of assays in use, especially for aPTT testing, and variable outcomes in reported numerical values with these assays when assessing proficiency samples. dRVVT testing mostly comprised reagents from three main manufacturing suppliers, which also showed differences in numerical values for the same homogeneous tested samples. Nevertheless, despite the use of different test reagents and processes, >98% of participants correctly identified LA-negative samples as LA-negative and LA-positive samples as LA positive. We hope our findings, reflecting on the heterogeneity of test processes and test data, help improve diagnostic testing for LA in the future.

Keywords

lupus anticoagulant - antiphospholipid antibodies - antiphospholipid syndrome - diagnosis - exclusion - laboratory testing - interpretation - external quality assessment - proficiency testing - random errors - test variability


Publikationsverlauf

Artikel online veröffentlicht:
15. November 2023

© 2023. Thieme. All rights reserved.

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  • References

  • 1 Barbhaiya M, Zuily S, Naden R. et al. ACR/EULAR APS Classification Criteria Collaborators. 2023 ACR/EULAR antiphospholipid syndrome classification criteria. Ann Rheum Dis 2023; (e-pub ahead of print)
    CrossrefPubMedSuche in Google Scholar
  • 2 Miyakis S, Lockshin MD, Atsumi T. et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 4 (02) 295-306
    CrossrefPubMedSuche in Google Scholar
  • 3 Devreese KMJ, de Groot PG, de Laat B. et al. Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis: update of the guidelines for lupus anticoagulant detection and interpretation. J Thromb Haemost 2020; 18 (11) 2828-2839
    CrossrefPubMedSuche in Google Scholar
  • 4 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; 7 (10) 1737-1740
    CrossrefPubMedSuche in Google Scholar
  • 5 Clinical and Laboratory Standards Institute (CLSI). Laboratory Testing for the Lupus Anticoagulant; Approved Guideline. CLSI document H60-A. Wayne, PA: CLSI; 2014
    Suche in Google Scholar
  • 6 Arachchillage DRJ, Gomez K, Alikhan R, Anderson JAM, Lester W, Laffan M. British Society for Haematology Haemostasis and Thrombosis Taskforce. 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 (02) 212-215
    CrossrefPubMedSuche in Google Scholar
  • 7 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 (01) 47-58
    CrossrefPubMedSuche in Google Scholar
  • 8 Favaloro EJ, Pasalic L. Lupus anticoagulant testing during anticoagulation, including direct oral anticoagulants. Res Pract Thromb Haemost 2022; 6 (02) e12676
    CrossrefPubMedSuche in Google Scholar
  • 9 Tripodi A, Cohen H, Devreese KMJ. Lupus anticoagulant detection in anticoagulated patients. Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis. J Thromb Haemost 2020; 18 (07) 1569-1575
    CrossrefPubMedSuche in Google Scholar
  • 10 Favaloro EJ, Bonar R, Marsden K. Internal quality control and external quality assurance in testing for antiphospholipid antibodies: part II–Lupus anticoagulant. Semin Thromb Hemost 2012; 38 (04) 404-411
    Thieme ConnectPubMedSuche in Google Scholar
  • 11 Favaloro EJ, Bonar R, Zebeljan D, Kershaw G, Marsden K. Laboratory investigation of lupus anticoagulants: mixing studies are sometimes required. J Thromb Haemost 2010; 8 (12) 2828-2831
    CrossrefPubMedSuche in Google Scholar
  • 12 Favaloro EJ, Bonar R, Marsden K. Lupus anticoagulant testing—sometimes mixing is required: potential for false negatives without mixing studies. Blood Coagul Fibrinolysis 2013; 24 (06) 673-676
    CrossrefPubMedSuche in Google Scholar
  • 13 Favaloro EJ, Wheatland L, Jovanovich S, Roberts-Thomson P, Wong RCW. Internal quality control and external quality assurance in testing for antiphospholipid antibodies: part I—anticardiolipin and anti-β2-glycoprotein I antibodies. Semin Thromb Hemost 2012; 38 (04) 390-403
    Thieme ConnectPubMedSuche in Google Scholar
  • 14 Bonar R, Favaloro E, Zebeljan D. et al. Evaluating laboratory approaches to the identification of lupus anticoagulants: a diagnostic challenge from the RCPA Haematology QAP. Pathology 2012; 44 (03) 240-247
    CrossrefPubMedSuche in Google Scholar
  • 15 Favaloro EJ, Bonar R, Sioufi J. et al. (on behalf of the RCPA QAP in Haematology). Multi-laboratory testing of thrombophilia: current and past practice in Australasia as assessed through the Royal College of Pathologists of Australasia Quality Assurance Program in Haematology. Semin Thromb Hemost 2005; 31 (01) 49-58
    Thieme ConnectPubMedSuche in Google Scholar
  • 16 Dembitzer FR, Ledford Kraemer MR, Meijer P, Peerschke EI. Lupus anticoagulant testing: performance and practices by north American clinical laboratories. Am J Clin Pathol 2010; 134 (05) 764-773
    CrossrefPubMedSuche in Google Scholar
  • 17 van den Besselaar AM, Devreese KM, de Groot PG, Castel A. Lupus anticoagulant: case-based external quality assessment. J Clin Pathol 2009; 62 (08) 731-734
    CrossrefPubMedSuche in Google Scholar
  • 18 Jennings I, Mackie I, Arnout J, Preston FE. UK National External Quality Assessment Scheme for Blood Coagulation. Lupus anticoagulant testing using plasma spiked with monoclonal antibodies: performance in the UK NEQAS proficiency testing programme. J Thromb Haemost 2004; 2 (12) 2178-2184
    CrossrefPubMedSuche in Google Scholar
  • 19 Jennings I, Greaves M, Mackie IJ, Kitchen S, Woods TA, Preston FE. UK National External Quality Assessment Scheme for Blood Coagulation. Lupus anticoagulant testing: improvements in performance in a UK NEQAS proficiency testing exercise after dissemination of national guidelines on laboratory methods. Br J Haematol 2002; 119 (02) 364-369
    CrossrefPubMedSuche in Google Scholar
  • 20 Arnout J, Meijer P, Vermylen J. Lupus anticoagulant testing in Europe: an analysis of results from the first European Concerted Action on Thrombophilia (ECAT) survey using plasmas spiked with monoclonal antibodies against human beta2-glycoprotein I. Thromb Haemost 1999; 81 (06) 929-934
    Thieme ConnectPubMedSuche in Google Scholar
  • 21 Favaloro EJ, Mohammed S, Vong R. et al. A multi-laboratory assessment of lupus anticoagulant assays performed on the ACL TOP 50 family for harmonized testing in a large laboratory network. Int J Lab Hematol 2022; 44 (03) 654-665
    CrossrefPubMedSuche in Google Scholar
  • 22 Efthymiou M, Mackie IJ, Lane PJ. et al; APS ACTION. Comparison of real world and core laboratory lupus anticoagulant results from the Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) clinical database and repository. J Thromb Haemost 2019; 17 (12) 2069-2080
    CrossrefPubMedSuche in Google Scholar
  • 23 Sciascia S, Radin M, Cecchi I. et al. Reliability of lupus anticoagulant and anti-phosphatidylserine/prothrombin autoantibodies in antiphospholipid syndrome: a multicenter study. Front Immunol 2019; 10: 376
    CrossrefPubMedSuche in Google Scholar
  • 24 Poz A, Pradella P, Azzarini G. et al. Lupus anticoagulant: a multicenter study for a standardized and harmonized reporting. Blood Coagul Fibrinolysis 2016; 27 (02) 176-184
    CrossrefPubMedSuche in Google Scholar
  • 25 Favaloro EJ, Wong RCW. Antiphospholipid antibody testing for the antiphospholipid syndrome: a synopsis of challenges and recent guidelines. Pathology 2014; 46 (06) 481-495
    CrossrefPubMedSuche in Google Scholar
  • 26 Jennings I, Kitchen DP, Kitchen S, Woods TA, Walker ID. Investigation of a prolonged APTT. Different approaches taken by laboratories to achieve the same diagnosis. Int J Lab Hematol 2013; 35 (02) 177-182
    CrossrefPubMedSuche in Google Scholar
  • 27 Favaloro EJ, Mohammed S, Curnow J, Pasalic L. Laboratory testing for lupus anticoagulant (LA) in patients taking direct oral anticoagulants (DOACs): potential for false positives and false negatives. Pathology 2019; 51 (03) 292-300
    CrossrefPubMedSuche in Google Scholar
  • 28 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: 10-19
    CrossrefPubMedSuche in Google Scholar
  • 29 Bonar R, Favaloro EJ, Mohammed S, Pasalic L, Sioufi J, Marsden K. The effect of dabigatran on haemostasis tests: a comprehensive assessment using in vitro and ex vivo samples. Pathology 2015; 47 (04) 355-364
    CrossrefPubMedSuche in Google Scholar
  • 30 Bonar R, Favaloro EJ, Mohammed S. et al. 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 (01) 60-71
    CrossrefPubMedSuche in Google Scholar