Erivelton de Azevedo Lopes1, Gustavo Guimarães Moreira Balbi1,2, Maria G Tektonidou3, Vittorio Pengo4, Savino Sciascia5, Amaia Ugarte6, H Michael Belmont7, Maria Gerosa8, Paul R Fortin9, Chary Lopez-Pedrera10, Lanlan Ji11, Hannah Cohen12, Guilherme Ramires de Jesús13, D Ware Branch14, Cecilia Nalli15, Michelle Petri16, Esther Rodriguez17, Nina Kello18, Roberto Ríos-Garcés19, Jason S Knight20, Tatsuya Atsumi21, Rohan Willis22, Maria Laura Bertolaccini23, Doruk Erkan24, Danieli Andrade25. 1. University of São Paulo, Av. Dr. Arnaldo 455, Third Floor, Room 3109, São Paulo, 01246903, Brazil. 2. Federal University of Juiz de Fora, Minas Gerais, Brazil. 3. National and Kapodistrian University of Athens, Athens, Greece. 4. University Hospital Padova, Padua, Italy. 5. Center of Research of Immunopathology and Rare Diseases, University of Turin, Turin, Italy. 6. Hospital Universitario Cruces, Barakaldo, País Vasco, Spain. 7. Hospital for Joint Diseases, New York University, New York, NY, USA. 8. Clinical Immunology and Rheumatology Unit, IRCCS Istituto Auxologico Italiano, Milan, Italy. 9. CHU de Québec-Université Laval, Québec, QC, Canada. 10. Rheumatology Service, IMIBIC/Reina Sofia Hospital, University of Cordoba, Cordoba, Spain. 11. Rheumatology and Immunology Department, Peking University First Hospital, Beijing, China. 12. Haemostasis Research Unit, Department of Haematology, University College London, London, UK. 13. Universidade Do Estado Do Rio de Janeiro, Rio de Janeiro, Brazil. 14. University of Utah and Intermountain Healthcare, Salt Lake City, UT, USA. 15. Rheumatology and Immunology Unit, ASST Spedali Civili of Brescia, Brescia, Italy. 16. Johns Hopkins University School of Medicine, Baltimore, MD, USA. 17. Hospital Universitario, 12 de Octubre, Madrid, Spain. 18. Northwell Health, Great Neck, NY, USA. 19. Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Catalonia, Spain. 20. Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA. 21. Hokkaido University Hospital, Sapporo, Japan. 22. Antiphospholipid Standardization Laboratory, University of Texas Medical Branch, Galveston, TX, USA. 23. Academic Department of Vascular Surgery, King's College London British Heart Foundation Centre of Excellence, School of Cardiovascular Medicine and Sciences, London, UK. 24. Barbara Volcker Center for Women and Rheumatic Disease, Hospital for Special Surgery, Weill Cornell Medicine, New York, NY, USA. 25. University of São Paulo, Av. Dr. Arnaldo 455, Third Floor, Room 3109, São Paulo, 01246903, Brazil. danieli.andrade@hc.fm.usp.br.
Abstract
BACKGROUND: Antiphospholipid syndrome (APS) is characterized by episodes of thrombosis, obstetric morbidity or both, associated with persistently positive antiphospholipid antibodies (aPL). Studying the profile of a rare disease in an admixed population is important as it can provide new insights for understanding an autoimmune disease. In this sense of miscegenation, Brazil is characterized by one of the most heterogeneous populations in the world, which is the result of five centuries of interethnic crosses of people from three continents. The objective of this study was to compare the clinical and laboratory characteristics of Brazilian vs. non-Brazilian primary antiphospholipid syndrome (PAPS) patients. METHODS: We classified PAPS patients into 2 groups: Brazilian PAPS patients (BPAPS) and PAPS patients from other countries (non-BPAPS). They were compared regarding demographic characteristics, criteria and non-criteria APS manifestations, antiphospholipid antibody (aPL) profile, and the adjusted Global Antiphospholipid Syndrome Score (aGAPSS). RESULTS: We included 415 PAPS patients (88 [21%] BPAPS and 327 [79%] non-BPAPS). Brazilian patients were significantly younger, more frequently female, sedentary, obese, non-white, and had a higher frequency of livedo (25% vs. 10%, p < 0.001), cognitive dysfunction (21% vs. 8%, p = 0.001) and seizures (16% vs. 7%, p = 0.007), and a lower frequency of thrombocytopenia (9% vs. 18%, p = 0.037). Additionally, they were more frequently positive for lupus anticoagulant (87.5% vs. 74.6%, p = 0.01), and less frequently positive to anticardiolipin (46.6% vs. 73.7%, p < 0.001) and anti-ß2-glycoprotein-I (13.6% vs. 62.7%, p < 0.001) antibodies. Triple aPL positivity was also less frequent (8% vs. 41.6%, p < 0.001) in Brazilian patients. Median aGAPSS was lower in the Brazilian group (8 vs. 10, p < 0.0001). In the multivariate analysis, BPAPS patients still presented more frequently with livedo, cognitive dysfunction and sedentary lifestyle, and less frequently with thrombocytopenia and triple positivity to aPL. They were also less often white. CONCLUSIONS: Our study suggests a specific profile of PAPS in Brazil with higher frequency of selected non-criteria manifestations and lupus anticoagulant positivity. Lupus anticoagulant (not triple positivity) was the major aPL predictor of a classification criteria event.
BACKGROUND: Antiphospholipid syndrome (APS) is characterized by episodes of thrombosis, obstetric morbidity or both, associated with persistently positive antiphospholipid antibodies (aPL). Studying the profile of a rare disease in an admixed population is important as it can provide new insights for understanding an autoimmune disease. In this sense of miscegenation, Brazil is characterized by one of the most heterogeneous populations in the world, which is the result of five centuries of interethnic crosses of people from three continents. The objective of this study was to compare the clinical and laboratory characteristics of Brazilian vs. non-Brazilian primary antiphospholipid syndrome (PAPS) patients. METHODS: We classified PAPS patients into 2 groups: Brazilian PAPS patients (BPAPS) and PAPS patients from other countries (non-BPAPS). They were compared regarding demographic characteristics, criteria and non-criteria APS manifestations, antiphospholipid antibody (aPL) profile, and the adjusted Global Antiphospholipid Syndrome Score (aGAPSS). RESULTS: We included 415 PAPS patients (88 [21%] BPAPS and 327 [79%] non-BPAPS). Brazilian patients were significantly younger, more frequently female, sedentary, obese, non-white, and had a higher frequency of livedo (25% vs. 10%, p < 0.001), cognitive dysfunction (21% vs. 8%, p = 0.001) and seizures (16% vs. 7%, p = 0.007), and a lower frequency of thrombocytopenia (9% vs. 18%, p = 0.037). Additionally, they were more frequently positive for lupus anticoagulant (87.5% vs. 74.6%, p = 0.01), and less frequently positive to anticardiolipin (46.6% vs. 73.7%, p < 0.001) and anti-ß2-glycoprotein-I (13.6% vs. 62.7%, p < 0.001) antibodies. Triple aPL positivity was also less frequent (8% vs. 41.6%, p < 0.001) in Brazilian patients. Median aGAPSS was lower in the Brazilian group (8 vs. 10, p < 0.0001). In the multivariate analysis, BPAPS patients still presented more frequently with livedo, cognitive dysfunction and sedentary lifestyle, and less frequently with thrombocytopenia and triple positivity to aPL. They were also less often white. CONCLUSIONS: Our study suggests a specific profile of PAPS in Brazil with higher frequency of selected non-criteria manifestations and lupus anticoagulant positivity. Lupus anticoagulant (not triple positivity) was the major aPL predictor of a classification criteria event.
Authors: Dongmei Yin; Philip G de Groot; Marisa Ninivaggi; Katrien M J Devreese; Bas de Laat Journal: Thromb Haemost Date: 2021-03-03 Impact factor: 6.681