Clinical Delphi on aPL Negativization: Report from the APS Study Group of the Italian Society for Rheumatology (SIR-APS)

Abstract Background  The rate of antiphospholipid antibody (aPL) negativization in antiphospholipid syndrome (APS) patients is uncertain, but it is estimated to be as high as 8%. Currently, a consensus definition of aPL negativization is lacking, as well as international recommendations on how to approach treatment in patients with a persistent aPL-negative seroconversion. Aim  The aim of the Delphi survey was to evaluate the clinical approach and level of consensus among experts from the APS Study Group of the Italian Society for Rheumatology (SIR-APS) in different clinical scenarios. Methods  Experts of SIR-APS were contacted using a survey methodology. Results  A structured survey was circulated among 30 experts. Up to 90% of the interviewed experts agreed on defining aPL negativization as the presence of two negative determinations, 1 year apart (90%). Almost full consensus exists among experts in some clinical settings, including: (1) the role of aPL negativization in the management of a thrombotic event determined by concomitant presence of cardiovascular risk factors, both modifiable and not modifiable (90%); (2) approach to young patients with triple aPL positivity who experienced pulmonary arterial thrombotic events and tested negative for aPL detection after 5 years of vitamin K antagonist (VKA) treatment (90%); (3) the use of “ extra criteria ” aPL antibody testing before pondering VKA suspension (93%). Conclusion  A substantial agreement exists among experts on how to define aPL negativization. VKA suspension should be embraced with extreme caution, particularly in case of previous thrombotic events and/or triple aPL positivity. Nevertheless, VKA cessation might be considered when risk factors are carefully monitored/treated and the presence of “ extra criteria ” aPL is ruled out.

[1]  M. Gatto,et al.  Prevalence, outcome and management of patients with SLE and secondary antiphospholipid antibody syndrome after aPL seroconversion. , 2020, Rheumatology.

[2]  D. Roccatello,et al.  Antiphosphatidylserine/Prothrombin Antibodies: An Update on Their Association with Clinical Manifestations of Antiphospholipid Syndrome , 2020, Thrombosis and Haemostasis.

[3]  P. Sfikakis,et al.  The effect of hydroxychloroquine on thrombosis prevention and antiphospholipid antibody levels in primary antiphospholipid syndrome: A pilot open label randomized prospective study. , 2020, Autoimmunity reviews.

[4]  V. Pengo,et al.  Tetra positive thrombotic antiphospholipid syndrome: Major contribution of anti‐phosphatidyl‐serine/prothrombin antibodies to lupus anticoagulant activity , 2020, Journal of thrombosis and haemostasis : JTH.

[5]  Liyan Wan,et al.  Anti-β2GPI domain 1 antibodies stratify high risk of thrombosis and late pregnancy morbidity in a large cohort of Chinese patients with antiphospholipid syndrome. , 2019, Thrombosis research.

[6]  E. Samoli,et al.  Effect of belimumab treatment on antiphospholipid antibody levels: post-hoc analysis based on two randomised placebo-controlled trials in systemic lupus erythematosus , 2019, Annals of the rheumatic diseases.

[7]  R. Wong,et al.  A review of 10 years of data from an external quality assurance program for antiphospholipid antibodies: no evidence for improved aCL and β2GPI assay standardization , 2019 .

[8]  D. Roccatello,et al.  Prevalence of Antiphospholipid Antibodies Negativisation in Patients with Antiphospholipid Syndrome: A Long-Term Follow-Up Multicentre Study , 2019, Thrombosis and Haemostasis.

[9]  A. Tincani,et al.  Autoantibodies’ titre modulation by anti-BlyS treatment in systemic lupus erythematosus , 2019, Lupus.

[10]  M. Ward,et al.  EULAR recommendations for the management of antiphospholipid syndrome in adults , 2019, Annals of the rheumatic diseases.

[11]  E. Silvestri,et al.  Belimumab reduces antiphospholipid antibodies in SLE patients independently of hydroxychloroquine treatment. , 2019, Autoimmunity reviews.

[12]  D. Roccatello,et al.  Anticardiolipin and anti-beta 2 glycoprotein-I antibodies disappearance in patients with systemic lupus erythematosus and antiphospholipid syndrome while on belimumab , 2018, Annals of the rheumatic diseases.

[13]  S. Sciascia,et al.  Can we withdraw anticoagulation in patients with antiphospholipid syndrome after seroconvertion? , 2017, Autoimmunity reviews.

[14]  D. Roccatello,et al.  Prevalence and Thrombotic Risk Assessment of Anti-β2 Glycoprotein I Domain I Antibodies: A Systematic Review , 2017, Seminars in Thrombosis and Hemostasis.

[15]  D. Roccatello,et al.  HYdroxychloroquine to Improve Pregnancy Outcome in Women with AnTIphospholipid Antibodies (HYPATIA) Protocol: A Multinational Randomized Controlled Trial of Hydroxychloroquine versus Placebo in Addition to Standard Treatment in Pregnant Women with Antiphospholipid Syndrome or Antibodies , 2017, Seminars in Thrombosis and Hemostasis.

[16]  L. Jara,et al.  Antiphospholipid antibodies disappearance in primary antiphospholipid syndrome: Thrombosis recurrence. , 2017, Autoimmunity reviews.

[17]  O. Decaux,et al.  Cessation of oral anticoagulants in antiphospholipid syndrome , 2017, Lupus.

[18]  Chrong-Reen Wang,et al.  Rituximab usage in systemic lupus erythematosus-associated antiphospholipid syndrome: A single-center experience. , 2016, Seminars in arthritis and rheumatism.

[19]  D. Roccatello,et al.  The efficacy of hydroxychloroquine in altering pregnancy outcome in women with antiphospholipid antibodies , 2015, Thrombosis and Haemostasis.

[20]  M. Galli.  Treatment of the antiphospholipid syndrome , 2013, Autoimmunity Highlights.

[21]  D. Roccatello,et al.  GAPSS: the Global Anti-Phospholipid Syndrome Score. , 2013, Rheumatology.

[22]  G. Espinosa,et al.  Discontinuation of anticoagulation or antiaggregation treatment may be safe in patients with primary antiphospholipid syndrome when antiphospholipid antibodies became persistently negative , 2013, Immunologic research.

[23]  D. Roccatello,et al.  Clinical accuracy for diagnosis of antiphospholipid syndrome in systemic lupus erythematosus: evaluation of 23 possible combinations of antiphospholipid antibody specificities , 2012, Journal of thrombosis and haemostasis : JTH.

[24]  Takao Koike,et al.  Efficacy of the antiphospholipid score for the diagnosis of antiphospholipid syndrome and its predictive value for thrombotic events. , 2012, Arthritis and rheumatism.

[25]  D. Roccatello,et al.  Treatment-induced downregulation of antiphospholipid antibodies: effect of rituximab alone on clinical and laboratory features of antiphospholipid syndrome , 2011, Lupus.

[26]  P. Meroni,et al.  Pathogenesis of antiphospholipid syndrome: understanding the antibodies , 2011, Nature Reviews Rheumatology.

[27]  J. Douketis,et al.  Evidence and clinical judgment: Treatment of cerebral vein thrombosis , 2010, Thrombosis and Haemostasis.

[28]  S. Iliceto,et al.  Clinical course of high‐risk patients diagnosed with antiphospholipid syndrome , 2010, Journal of thrombosis and haemostasis : JTH.

[29]  Á. Blanco-Molina,et al.  Retirada de la anticoagulación en el síndrome antifosfolípido primario cuando se negativizan los anticuerpos anticardiolipina , 2008 .

[30]  Y. Shoenfeld,et al.  International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS) , 2006, Journal of thrombosis and haemostasis : JTH.

[31]  E. Harris,et al.  The antiphospholipid syndrome , 1995, Clinical reviews in allergy & immunology.