Clinical and Prognostic Significance of Non-criteria Antiphospholipid Antibody Tests

Bertolaccini, María Laura; Amengual, Olga; Artim-Eser, Bahar; Atsumi, Tatsuya; Groot, Philip G. de; Laat, Bas de; Devreese, Katrien; Giles, Ian; Meroni, Pier Luigi; Borghi, María Orietta; Rahman, Anisur; Rand, Jacob H.; Régnault, V.; Kumar, Rajesh; Tincani, Anǵela; Wahl, Denis; Zuily, Stéphane; Sanna, Giovanni

doi:10.1007/978-3-319-55442-6_8

Cited by 4 publications

(4 citation statements)

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“…The inclusion of aPS/PT antibodies as a laboratory criterion of APS has been previously considered by our task force and deemed unwarranted because of poor standardization of the available assays and because reproducibility of the strong correlations between aPS/PT and APS manifestations needed confirmation in larger studies. 4 Anti-phosphatidylserine/prothrombin (aPS/PT) antibodies are a low affinity heterogeneous class of antibodies directed against a complex of negatively charged phospholipid, other than cardiolipin and prothrombin (PT). The methodology for their detection has improved over the years and currently aPS/ PT antibodies are identified by enzyme immunosorbent assays using prothrombin in complex with phosphatidylserine in the presence of calcium.…”

Section: Phosphatidylserine-dependent Antiprothrombin Antibodies (Aps...mentioning

confidence: 99%

Section: Phosphatidylserine-dependent Antiprothrombin Antibodies (Aps...mentioning

confidence: 99%

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16th International congress on antiphospholipid antibodies task force report on antiphospholipid syndrome laboratory diagnostics and trends

Atsumi,

Chighizola,

Fujieda

et al. 2023

Lupus

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Classification criteria for antiphospholipid syndrome (APS) require IgG or IgM isotypes of the anticardiolipin (aCL) antibodies, anti-β2 glycoprotein I (anti-β2GPI) antibodies, and/or the lupus anticoagulant (LA) to satisfy the laboratory disease definition. Over the past 20 years, non-criteria antiphospholipid antibodies (aPL) directed to other proteins of the coagulation cascade (i.e. prothrombin and/or phosphatidylserine–prothrombin complex) or to some domains of β2GPI have been proposed. This task force concentrated and reviewed the literature on data including aPS/PT, antibodies to domain 4/5 of β2GPI and the newly described antibodies to protein/HLA-DR complex. In addition, we discussed testing of LA in the ‘new’ oral anticoagulants’ era and the value of triple positivity in the risk assessment of aPL. The conclusions were presented at a special session during the 16th International Congress on aPL, Manchester, UK, September 2019.

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Section: Phosphatidylserine-dependent Antiprothrombin Antibodies (Aps...mentioning

confidence: 99%

Section: Phosphatidylserine-dependent Antiprothrombin Antibodies (Aps...mentioning

confidence: 99%

16th International congress on antiphospholipid antibodies task force report on antiphospholipid syndrome laboratory diagnostics and trends

Atsumi,

Chighizola,

Fujieda

et al. 2023

Lupus

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“…14,15 Several noncriteria aPL, such as antiphosphatidylserine/prothrombin (aPS/PT) IgG/IgM and the IgA isotypes of aCL and aβ2GPI are not included in the current APS classification criteria, 14 but at times still identify individuals with APS-related clinical manifestations. 6,15 aPS/PT recognizes prothrombin complexes with anionic phosphatidylserine and associates closely with positive lupus anticoagulant testing. 7 A systematic review of 10 retrospective studies found a significant association between aPS/PT positivity and thromboembolic events.…”

Section: Introductionmentioning

confidence: 98%

“…Antiphospholipid antibodies (aPL) are an important but heterogeneous group of autoantibodies that activate endothelial cells, platelets, and neutrophils via interactions with cellassociated phospholipids and phospholipid-binding proteins such as beta-2-glycoprotein I (β2GPI) and prothrombin. [6][7][8][9][10][11] Antiphospholipid syndrome (APS) is an acquired thromboinflammatory disease characterized by arterial, venous, and microvascular thrombotic events and obstetric complications in the presence of persistently circulating aPL. 12 In patients with APS, arterial occlusions leading to stroke and myocardial infarction are among the most common causes of morbidity and mortality.…”

Section: Introductionmentioning

confidence: 99%

Prevalence of Antiphospholipid Antibodies and Association With Incident Cardiovascular Events

et al. 2023

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ImportanceThe prevalence of antiphospholipid antibodies (aPL) and their association with future atherosclerotic cardiovascular disease (ASCVD) risk has yet to be thoroughly investigated.ObjectiveTo determine the association between measurements of aPL at a single time point and ASCVD risk in a diverse population.Design, Setting, and ParticipantsThis cohort study measured 8 aPL (anticardiolipin [aCL] IgG/IgM/IgA, anti–beta-2 glycoprotein I [aβ2GPI] IgG/IgM/IgA, and antiphosphatidylserine/prothrombin [aPS/PT] IgG/IgM) by solid-phase assays in plasma from participants of the Dallas Heart Study (DHS) phase 2, a multiethnic, population-based cohort study. Blood samples were collected between 2007 and 2009. The median follow-up was 8 years. Statistical analysis was performed from April 2022 to January 2023.Main Outcomes and MeasuresAssociations of aPL with future ASCVD events (defined as first nonfatal myocardial infarction, first nonfatal stroke, coronary revascularization, or death from cardiovascular cause) were assessed by Cox proportional hazards models, adjusting for known risk factors, medications, and multiple comparisons.ResultsAmong the 2427 participants (mean [SD] age, 50.6 [10.3] years; 1399 [57.6%] female; 1244 [51.3%] Black, 339 [14.0%] Hispanic, and 796 [32.8%] White), the prevalence of any positive aPL tested at a single time point was 14.5% (353 of 2427), with approximately one-third of those detected at a moderate or high titer; aCL IgM had the highest prevalence (156 individuals [6.4%]), followed by aPS/PT IgM (88 [3.4%]), aβ2GPI IgM (63 [2.6%]), and aβ2GPI IgA (62 [2.5%]). The IgA of aCL (adjusted hazard ratio [HR], 4.92; 95% CI, 1.52-15.98) and aβ2GPI (HR, 2.91; 95% CI, 1.32-6.41) were independently associated with future ASCVD events. The risk further increased when applying a positivity threshold of at least 40 units (aCL IgA: HR, 9.01 [95% CI, 2.73-29.72]; aβ2GPI IgA: HR, 4.09 [95% CI, 1.45-11.54]). Levels of aβ2GPI IgA negatively correlated with cholesterol efflux capacity (r = −0.055; P = .009) and positively correlated with circulating oxidized LDL (r = 0.055; P = .007). aβ2GPI IgA–positive plasma was associated with an activated endothelial cell phenotype as evidenced by increased surface expression of surface E-selectin, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1.Conclusions and RelevanceIn this population-based cohort study, aPL detectable by solid-phase assays were present in a substantial proportion of adults; positive aCL IgA and aβ2GPI IgA at a single time point were independently associated with future ASCVD events. Longitudinal studies with serial aPL measurements are needed to further explore these findings.

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Treatment of thrombotic antiphospholipid syndrome in adults and children

Madison

Duarte‐García

Zuo

et al. 2020

Current Opinion in Rheumatology

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Purpose of review Antiphospholipid syndrome (APS), more common than once believed, is an autoimmune disease best known for its high risk of incident and recurrent thrombotic events. The approach to treatment potentially differs from treatment of thrombosis in the general population, and this article endeavors to review the latest updates on this topic. Recent findings The epidemiology of APS is being increasingly elucidated by large population-based studies, with APS perhaps affecting as many as 1 in 2000 individuals. Vitamin K antagonists, aspirin, and heparinoids continue to have obvious roles in the management of patients with APS. There has recently been intensive study of direct oral anticoagulants in APS, with the most recent randomized studies raising concerns about their inferiority to vitamin K antagonists, at least in some subgroups. Other approaches to treating APS beyond anticoagulants and antiaggregants are also receiving increased attention in mechanistic and preclinical studies with an eye toward future roles in patients with refractory and/or microvascular disease. Pediatric APS is identified as an area in desperate need of additional prospective research. Summary Progress continues to be made in pursuit of improving the lives of individuals afflicted with APS. The most important future directions would seem to involve leveraging modern molecular technologies in order to improve subphenotyping of antiphospholipid antibody-positive individuals. This will help personalize risk profiles and ideally define the optimal approach to therapy based on future risk, rather than past morbid events.

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Clinical and Prognostic Significance of Non-criteria Antiphospholipid Antibody Tests

Cited by 4 publications

References 86 publications

16th International congress on antiphospholipid antibodies task force report on antiphospholipid syndrome laboratory diagnostics and trends

16th International congress on antiphospholipid antibodies task force report on antiphospholipid syndrome laboratory diagnostics and trends

Prevalence of Antiphospholipid Antibodies and Association With Incident Cardiovascular Events

Treatment of thrombotic antiphospholipid syndrome in adults and children

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