Maria Efthymiou1, Ian J Mackie1, Philip J Lane1, Danieli Andrade2, Rohan Willis3, Doruk Erkan4, Savino Sciascia5, Steven Krillis6, Elisa Bison7, Margarete Borges Galhardo Vendramini2, Zurina Romay-Penabad3, Miao Qi6, Maria Tektonidou8, Amaia Ugarte9, Cecilia Chighizola10, H Michael Belmont11, Maria Angeles Aguirre12, Lanlan Ji13, D Ware Branch14, Guilherme de Jesus15, Paul R Fortin16, Laura Andreoli17,18, Michelle Petri19, Ricard Cervera20, Esther Rodriguez21, Jason S Knight22, Tatsuya Atsumi23, Joann Vega7, Ecem Sevim7, Maria Laura Bertolaccini24, Vittorio Pengo6, Hannah Cohen1,25. 1. Haemostasis Research Unit, Department of Haematology, University College London, London, UK. 2. University of Sao Paulo, Sao Paulo, Brazil. 3. Antiphospholipid Standardization Laboratory, University of Texas Medical Branch, Galveston, TX, USA. 4. Barbara Volcker Center for Women and Rheumatic Diseases, Hospital for Special Surgery, Weill Cornell Medicine, New York, NY, USA. 5. Center of Research of Immunopathology and Rare Diseases, University of Turin, Turin, Italy. 6. Department of Infectious Diseases, Immunology and Sexual Health, St George Hospital, Sydney, NSW, Australia. 7. University Hospital Padova, Padova, Italy. 8. National and Kapodistrian University of Athens, Athens, Greece. 9. Internal Medicine, Hospital Universitario Cruces, Barakaldo, País Vasco, Spain. 10. University of Milan, Milan, Italy. 11. School of Medicine, New York University, New York, NY, USA. 12. Maimonides Institute for Biomedical Research of Cordoba, Cordoba, Spain. 13. Rheumatology and Immunology Department, Peking University First Hospital, Beijing, China. 14. University of Utah and Intermountain Healthcare, Salt Lake City, UT, USA. 15. Rio de Janeiro State University, Rio de Janeiro, Brazil. 16. CHU de Quebec - Université Laval, Quebec, QC, Canada. 17. Rheumatology and Clinical Immunology, Spedali Civili, Brescia, Italy. 18. Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy. 19. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. 20. Department of Autoimmune Diseases, Hospital Clínic Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalonia, Spain. 21. Hospital Universitario 12 de Octubre, Madrid, Spain. 22. Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA. 23. Hokkaido University Hospital, Sapporo, Japan. 24. Academic Department of Vascular Surgery, School of Cardiovascular Medicine & Sciences, King's College London, London, UK. 25. Department of Haematology, University College London Hospitals NHS Foundation Trust, London, UK.
Abstract
BACKGROUND: Variability remains a challenge in lupus anticoagulant (LA) testing. OBJECTIVE: To validate LA test performance between Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) Core laboratories and examine agreement in LA status between Core and local/hospital laboratories contributing patients to this prospective registry. METHODS: Five Core laboratories used the same reagents, analyzer type, protocols, and characterized samples for LA validation. Non-anticoagulated registry samples were retested at the corresponding regional Core laboratories and anticoagulated samples at a single Core laboratory. Categorical agreement and discrepancies in LA status between Core and local/hospital laboratories were analyzed. RESULTS: Clotting times for the reference/characterized plasmas used for normalized ratios were similar between Core laboratories (CV <4%); precision and agreement for LA positive/negative plasma were similar (all CV ≤5%) in the four laboratories that completed both parts of the validation exercise; 418 registry samples underwent LA testing. Agreement for LA positive/negative status between Core and local/hospital laboratories was observed in 87% (115/132) non-anticoagulated and 77% (183/237) anticoagulated samples. However, 28.7% (120/418) of samples showed discordance between the Core and local/hospital laboratories or equivocal LA results. Some of the results of the local/hospital laboratories might have been unreliable in 24.7% (41/166) and 23% (58/252) of the total non-anticoagulated and anticoagulated samples, respectively. Equivocal results by the Core laboratory might have also contributed to discordance. CONCLUSIONS: Laboratories can achieve good agreement in LA performance by use of the same reagents, analyzer type, and protocols. The standardized Core laboratory results underpin accurate interpretation of APS ACTION clinical data.
BACKGROUND: Variability remains a challenge in lupus anticoagulant (LA) testing. OBJECTIVE: To validate LA test performance between Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) Core laboratories and examine agreement in LA status between Core and local/hospital laboratories contributing patients to this prospective registry. METHODS: Five Core laboratories used the same reagents, analyzer type, protocols, and characterized samples for LA validation. Non-anticoagulated registry samples were retested at the corresponding regional Core laboratories and anticoagulated samples at a single Core laboratory. Categorical agreement and discrepancies in LA status between Core and local/hospital laboratories were analyzed. RESULTS: Clotting times for the reference/characterized plasmas used for normalized ratios were similar between Core laboratories (CV <4%); precision and agreement for LA positive/negative plasma were similar (all CV ≤5%) in the four laboratories that completed both parts of the validation exercise; 418 registry samples underwent LA testing. Agreement for LA positive/negative status between Core and local/hospital laboratories was observed in 87% (115/132) non-anticoagulated and 77% (183/237) anticoagulated samples. However, 28.7% (120/418) of samples showed discordance between the Core and local/hospital laboratories or equivocal LA results. Some of the results of the local/hospital laboratories might have been unreliable in 24.7% (41/166) and 23% (58/252) of the total non-anticoagulated and anticoagulated samples, respectively. Equivocal results by the Core laboratory might have also contributed to discordance. CONCLUSIONS: Laboratories can achieve good agreement in LA performance by use of the same reagents, analyzer type, and protocols. The standardized Core laboratory results underpin accurate interpretation of APS ACTION clinical data.