JUNE 2023

apsaction aps Publications June 30, 2023

Damage measured by damage index for antiphosphlipid syndrome in antiphospholipid antibody-positive patients included in APS ACTION Registry.

Balbi GGM, Ahmadzadeh Y, Tektonidou MG, Pengo V, Sciascia S, Ugarte A, Belmont HM, Lopez-Pedrera C, Fortin PR, Wahl D, Gerosa M, de Jesús GR, Ji L, Atsumi T, Efthymiou M, Branch DW, Nalli C, Almaraz ER, Petri M, Cervera R, Knight JS, Artim-Esen B, Willis R, Bertolaccini ML, Cohen H, Roubey R, Erkan D, Andrade D; AntiPhospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) Clinical Database and Repository (APS ACTION).

Rheumatology (Oxford). 2023 Jun 12:kead292. doi: 10.1093/rheumatology/kead292. Online ahead of print.PMID: 37307082

————————————————–

Abstract

Objectives: Our primary objective was to quantify damage burden measured by Damage Index for Antiphospholipid Syndrome (DIAPS) in antiphospholipid antibody (aPL)-positive patients with or without a history of thrombosis in an international cohort. Secondly, we aimed to identify clinical and laboratory characteristics associated with damage in aPL-positive patients.

Methods: In this cross-sectional study, we analyzed the baseline damage in aPL-positive patients with or without APS classification. We excluded patients with other autoimmune diseases. We analyzed the demographic, clinical, and laboratory characteristics based on two subgroups: (1) thrombotic APS patients with high versus low damage; and (2) non-thrombotic aPL-positive patients with versus without damage.

Results: Of the 826 aPL-positive patients included in the registry as of April 2020, 576 with no other systemic autoimmune diseases were included in the analysis (412 thrombotic and 164 non-thrombotic). In the thrombotic group, hyperlipidemia (OR 1.82, 95%CI 1.05-3.15, adjusted p= 0.032), obesity (OR 2.14, 95%CI 1.23-3.71, adjusted p= 0.007), aβ2GPI high titers (OR 2.33, 95%CI 1.36-4.02, adjusted p= 0.002), and corticosteroids use (ever) (OR 3.73, 95%IC 1.80-7.75, adjusted p< 0.001) were independently associated with high damage at baseline. In the non-thrombotic group, hypertension (OR 4.55, 95%CI 1.82-11.35, adjusted p= 0.001) and hyperlipidemia (OR 4.32, 95%CI 1.37-13.65, adjusted p= 0.013) were independent predictors of damage at baseline; conversely, single aPL positivity was inversely correlated with damage (OR 0.24; 95%CI 0.075-0,77, adjusted p= 0.016).

Conclusions: DIAPS indicates substantial damage in aPL-positive patients in APS ACTION cohort. Selected traditional cardiovascular risk factors, steroids use and specific aPL profiles may help to identify patients more prone to present with a higher damage burden.

————————————————–

MAY 2023

apsaction aps Publications June 30, 2023

Associations Among Antiphospholipid Antibody Types, Isotypes, and Titers: An AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) Study.

Gkrouzman E, Willis R, Andrade D, Tektonidou MG, Pengo V, Ruiz-Irastorza G, Belmont HM, Fortin PR, Gerosa M, Signorelli F, Atsumi T, Branch DW, Nalli C, Rodriguez-Almaraz E, Petri MA, Cervera R, Knight JS, Efthymiou M, Cohen H, Bertolaccini ML, Erkan D, Roubey R; APS ACTION.

Lab Invest. 2023 Jun;103(6):100147. doi: 10.1016/j.labinv.2023.100147. Epub 2023 Apr 11.PMID: 37044248

————————————————–

Abstract

Several antiphospholipid antibody (aPL) profiles (“triple” and lupus anticoagulant [LA] positivity) are associated with a higher risk for clinical manifestations of antiphospholipid syndrome (APS). Further risk is correlated with higher levels of anticardiolipin antibody (aCL) and anti-β₂ glycoprotein-I antibody (aβ₂GPI), and with aPL persistence. Given that the 3 aPL tests detect partially overlapping sets of antibodies, the primary goal of this study was to characterize the associations among aPL tests using AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) core laboratory data. The APS ACTION Registry includes annually followed adult patients with positive aPL based on the Revised Sapporo Classification Criteria.

We analyzed baseline and prospective core laboratory data of the registry for associations among aPL tests using the Spearman rank correlation with Bonferroni-adjusted significance level for multiple comparisons. An aPL Load was calculated based on 6 tests (aCL IgG/IgM/IgA and aβ₂GPI IgG/IgM/IgA); a receiver operating characteristic curve was used to evaluate the diagnostic performance of the aPL Load in predicting LA positivity. In 351 patients simultaneously tested for LA, aCL, and aβ₂GPI, the frequency of moderate-to-high (≥40 U) titers of aCL and aβ₂GPI IgG/IgM/IgA was higher in patients who were positive for LA vs those who were negative. An aPL Load was calculated for each patient to assess the overall aPL burden. For every 1-point increase in the aPL Load, the possibility of a positive LA test increased by 32% (odds ratio, 1.32; 95% CI, 1.2-1.5; P < .001).

Based on core laboratory data from a large international registry, most aPL enzyme-linked immunosorbent assay ≥40 U and a high calculated aPL Load combining 6 aPL enzyme-linked immunosorbent assays were predictive of a positive LA. These data suggest that the combined quantitative burden of aPL may provide a mechanistic explanation of a positive LA.

————————————————–

MARCH 2023

apsaction aps Publications June 30, 2023

Anti-Neutrophil Extracellular Trap Antibodies in Antiphospholipid Antibody-Positive Patients: Results From the Antiphospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking Clinical Database and Repository.

Zuo Y, Navaz S, Tsodikov A, Kmetova K, Kluge L, Ambati A, Hoy CK, Yalavarthi S, de Andrade D, Tektonidou MG, Sciascia S, Pengo V, Ruiz-Irastorza G, Belmont HM, Gerosa M, Fortin PR, de Jesus GR, Branch DW, Andreoli L, Rodriguez-Almaraz E, Petri M, Cervera R, Willis R, Karp DR, Li QZ, Cohen H, Bertolaccini ML, Erkan D, Knight JS; Antiphospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking.

Arthritis Rheumatol. 2023 Mar 2. doi: 10.1002/art.42489. Online ahead of print. PMID: 36862141

————————————————–

Abstract

Objective: This study aimed to elucidate the presence, antigen specificities, and potential clinical associations of anti-neutrophil extracellular trap (anti-NET) antibodies in a multinational cohort of antiphospholipid (aPL) antibody-positive patients who did not have lupus.

Methods: Anti-NET IgG/IgM levels were measured in serum samples from 389 aPL-positive patients; 308 patients met the classification criteria for antiphospholipid syndrome. Multivariate logistic regression with best variable model selection was used to determine clinical associations. For a subset of the patients (n = 214), we profiled autoantibodies using an autoantigen microarray platform.

Results: We found elevated levels of anti-NET IgG and/or IgM in 45% of the aPL-positive patients. High anti-NET antibody levels are associated with more circulating myeloperoxidase (MPO)-DNA complexes, which are a biomarker of NETs. When considering clinical manifestations, positive anti-NET IgG was associated with lesions affecting the white matter of the brain, even after adjusting for demographic variables and aPL profiles. Anti-NET IgM tracked with complement consumption after controlling for aPL profiles; furthermore, patient serum samples containing high levels of anti-NET IgM efficiently deposited complement C3d on NETs. As determined by autoantigen microarray, positive testing for anti-NET IgG was significantly associated with several autoantibodies, including those recognizing citrullinated histones, heparan sulfate proteoglycan, laminin, MPO-DNA complexes, and nucleosomes. Anti-NET IgM positivity was associated with autoantibodies targeting single-stranded DNA, double-stranded DNA, and proliferating cell nuclear antigen.

Conclusion: These data reveal high levels of anti-NET antibodies in 45% of aPL-positive patients, where they potentially activate the complement cascade. While anti-NET IgM may especially recognize DNA in NETs, anti-NET IgG species appear to be more likely to target NET-associated protein antigens.

————————————————–

JANUARY 2023

apsaction aps Publications February 2, 2023

Fluctuation of Anti-Domain 1 and Anti-Β2 Glycoprotein I Antibody Titers Over Time in Patients with Persistently Positive Antiphospholipid Antibodies.

Chighizola CB, Pregnolato F, Andrade D, Tektonidou M, Pengo V, Ruiz-Irastorza G, Belmont HM, Gerosa M, Fortin P, Branch DW, Andreoli L, Petri MA, Cervera R, Knight JS, Willis R, Efthymiou M, Cohen H, Erkan D, Bertolaccini ML; AntiPhospholipid Syndrome Alliance For Clinical Trials and InternatiOnal Networking (APS ACTION).

Arthritis Rheumatol. 2023 Jan 27. doi: 10.1002/art.42459. Online ahead of print.PMID: 36704930

————————————————–

Abstract

Objective: This work aims at evaluating longitudinally titers of antibodies against β2-glycoprotein I (β2GPI) and domain 1 (anti-D1), identifying predictors of the variation of anti-D1 and anti-β2GPI antibody titers and clarifying whether antibody titer fluctuations predict thrombosis in a large international cohort of patients persistently positive for antiphospholipid antibodies (aPL), the “APS ACTION Registry”.

Methods: Patients with available blood samples from at least 4 time points were included. Anti-β2GPI and anti-D1 IgG were tested by chemiluminescence (BioFlash, INOVA Diagnostics).

Results: In a cohort of 230 patients, anti-D1 and anti-β2GPI titers decreased significantly over time (p<0.0001 and p=0.010, respectively). After adjustment for age, gender, and number of positive aPL tests, the fluctuation of anti-D1 and anti-β2GPI titers was associated with treatment with hydroxychloroquine (HCQ) at each time-point. Treatment with HCQ, but not immunosuppressors, was associated with 1.3-fold and 1.4-fold decrease in anti-D1 and anti-β2GPI titers, respectively. Incident vascular events were associated with 1.9-fold and 2.1-fold increase of anti-D1 and anti-β2GPI titers, respectively. Anti-D1 and anti-β2GPI titers at the time of thrombosis were lower compared to the other time-points: 1.6-fold decrease in anti-D1 titers and 2-fold decrease in anti-β2GPI titers conferred an OR for incident thrombosis of 6.0 (95%CI 0.62-59.3) and 9.4 (95%CI 1.1-80.2), respectively.

Conclusions: Treatment with HCQ and incident vascular events significant predicted anti-D1 and anti-β2GPI titer fluctuation over time. Both anti-D1 and anti-β2GPI titers drop around the time of thrombosis, with potential clinical relevance.

————————————————–

APS ACTION 13th ANNUAL SUMMIT (November 2022)

apsaction aps Publications November 25, 2022

13th APS ACTION Annual Summit (and the 3rd Virtual Summit) took place on November 17-18, 2022 with the participation of 60 APS ACTION members. The objective of this scientific meeting has been to foster international collaboration for future studies, and facilitate discussions of the ongoing projects. During the 2022 summit, Dr Shruti Chaturverdi, MBBS, MSCI also delivered the keynote speech on “Antiphospholipid Syndrome and Complement: Antibodies, Genes, and the Environment”

OCTOBER 2022

apsaction aps Publications October 11, 2022

Immunosuppression use in primary antiphospholipid antibody-positive patients: Descriptive analysis of the AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) Clinical Database and Repository (“Registry”).

Erton ZB, K Leaf R, de Andrade D, Clarke AE, Tektonidou MG, Pengo V, Sciascia S, Ugarte A, Belmont HM, Gerosa M, Fortin PR, Lopez-Pedrera C, Atsumi T, Zhang Z, Cohen H, Ramires de Jesús G, Branch DW, Wahl D, Andreoli L, Rodriguez-Almaraz E, Petri M, Barilaro G, Zuo Y, Artim-Esen B, Willis R, Quintana R, Vendramini MB, Barber MW, Bertolaccini ML, Roubey R, Erkan D.

Lupus. 2022 Oct 7:9612033221128742. doi: 10.1177/09612033221128742. Online ahead of print.PMID: 36206383

————————————————–

Abstract

Background/purpose: APS ACTION Registry was created to study the outcomes of patients with persistently positive antiphospholipid antibodies (aPL) with or without other systemic autoimmune disease (SAIDx). Given that immunosuppression (IS) is used for certain aPL manifestations, for example, thrombocytopenia (TP), our primary objective was to describe the indications for IS in aPL-positive patients without other SAIDx. Secondly, we report the type of IS used in patients with selected microvascular or non-thrombotic aPL manifestations.

Methods: An online database is used to collect clinical data. The inclusion criteria are positive aPL based on the laboratory section of the APS Classification Criteria, tested at least twice within one year prior to enrollment. Patients are followed every 12 ± 3 months. For this descriptive retrospective and prospective analysis, we included aPL-positive patients without other SAIDx and excluded those with new SAIDx classification during follow-up. For each patient, we retrieved clinical data at baseline and follow-up including selected aPL manifestations (diffuse alveolar hemorrhage [DAH], antiphospholipid-nephropathy [aPL-N], livedoid vasculopathy [LV]-related skin ulcers, TP, autoimmune hemolytic anemia [AIHA], cardiac valve disease [VD]), and IS medications.

Results: Of 899 patients enrolled, 537 were included in this analysis (mean age 45 ± 13 years, female 377 [70%], APS Classification in 438 [82%], and at least one selected microvascular or non-thrombotic aPL manifestation in 141 (26%)). Of 537 patients, 76 (14%) were reported to use IS (ever), and 41/76 (54%) received IS primarily for selected aPL manifestation. In six of 8 (75%) DAH patients, 6/19 (32%) aPL-N, 4/28 (14%) LV, 25/88 (28%) TP, 6/11 (55%) AIHA, and 1/43 (2%) VD, the IS (excluding corticosteroids/hydroxychloroquine) indication was specific for selected aPL manifestation.

Conclusion: In our international cohort, 14% of aPL-positive patients without other SAIDx were reported to receive IS; the indication was at least one of the selected microvascular and/or non-thrombotic aPL-related manifestations in half. Thrombocytopenia was the most frequent among those selected aPL-related manifestations; however, approximately one-third received IS specifically for that indication. Diffuse alveolar hemorrhage was frequently treated with IS followed by AIHA and aPL-N. Systematic controlled studies are urgently needed to better define the role of IS in APS.

————————————————–

JUNE 2022

apsaction aps Publications August 13, 2022August 13, 2022

Pregnancy outcomes in antiphospholipid antibody positive patients: prospective results from the AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION) Clinical Database and Repository (‘Registry’).

Erton ZB, Sevim E, de Jesús GR, Cervera R, Ji L, Pengo V, Ugarte A, Andrade D, Andreoli L, Atsumi T, Fortin PR, Gerosa M, Zuo Y, Petri M, Sciascia S, Tektonidou MG, Aguirre-Zamorano MA, Branch DW, Erkan D; APS ACTION.

Lupus Sci Med. 2022 Jun;9(1):e000633.

————————————————–

Abstract

Objectives: To describe the outcomes of pregnancies in antiphospholipid antibody (aPL)-positive patients since the inception of the AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking Registry.

Methods: We identified persistently aPL-positive patients recorded as ‘pregnant’ during prospective follow-up, and defined ‘aPL-related outcome’ as a composite of: (1) Preterm live delivery (PTLD) at or before 37th week due to pre-eclampsia (PEC), eclampsia, small-for-gestational age (SGA) and/or placental insufficiency (PI); or (2) Otherwise unexplained fetal death after the 10th week of gestation. The primary objective was to describe the characteristics of patients with and without aPL-related composite outcomes based on their first observed pregnancies following registry recruitment.

Results: Of the 55 first pregnancies observed after registry recruitment among nulliparous and multiparous participants, 15 (27%) resulted in early pregnancy loss <10 weeks gestation. Of the remaining 40 pregnancies: (1) 26 (65%) resulted in term live delivery (TLD), 4 (10%) in PTLD between 34.0 weeks and 36.6 weeks, 5 (12.5%) in PTLD before 34th week, and 5 (12.5%) in fetal death (two associated with genetic anomalies); and (2) The aPL-related composite outcome occurred in 9 (23%). One of 26 (4%) pregnancies with TLD, 3/4 (75%) with PTLD between 34.0 weeks and 36.6 weeks, and 3/5 (60%) with PTLD before 34th week were complicated with PEC, SGA and/or PI. Fifty of 55 (91%) pregnancies were in lupus anticoagulant positive subjects, as well as all pregnancies with aPL-related composite outcome.

Conclusion: In our multicentre, international, aPL-positive cohort, of 55 first pregnancies observed prospectively, 15 (27%) were complicated by early pregnancy loss. Of the remaining 40 pregnancies, composite pregnancy morbidity was observed in 9 (23%) pregnancies.

————————————————–

DECEMBER 2021

apsaction aps Publications January 9, 2022

COVID-19 and antiphospholipid antibodies: A position statement and management guidance from AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking (APS ACTION).

Wang X, Gkrouzman E, Andrade DCO, Andreoli L, Barbhaiya M, Belmont HM, Branch DW, de Jesús GR, Efthymiou M, Ríos-Garcés R, Gerosa M, El Hasbani G, Knight J, Meroni PL, Pazzola G, Petri M, Rand J, Salmon J, Tektonidou M, Tincani A, Uthman IW, Zuily S, Zuo Y, Lockshin M, Cohen H, and Erkan D on Behalf of APS ACTION.

Lupus. 2021 Dec 16:9612033211062523. doi: 10.1177/09612033211062523. Online ahead of print.

————————————————–

ARTICLE SUMMARY FOR PATIENTS by the lead author, Dr. Xin Wang

Coronavirus disease 2019 (COVID-19) is a viral infection caused by the SARS-CoV-2 virus, noted during the pandemic to be associated with a high rate of thrombosis (blood clots) in hospitalized patients. In addition, there have been reports of antiphospholipid antibody (aPL)-positive COVID-19 patients. Thus, similarities between COVID-19 and antiphospholipid syndrome (APS) raised the possibility of similar mechanisms, in particular, COVID-19 infection leading to widespread inflammation and small vessel blood clots in multiple organs, a characteristic of catastrophic antiphospholipid syndrome (CAPS).

APS ACTION members created an international multidisciplinary COVID-19 working group to examine: a) common mechanisms between APS and COVID-19; b) the significance of newly positive aPL tests during COVID-19 infection; and c) implications of the COVID-19 infection in aPL-positive patients with or without APS. In addition, the group also provided guidance for clinical management and monitoring of aPL positive COVID-19 patients.

Key Messages of the APS ACTION COVID-19 Working Group included in this recent publication are:

Common mechanisms between COVID-19 and APS exist, as it is seen in other pro-thrombotic disorders. For instance, injury of the cells lining blood vessel walls (endothelial cells) or excessive complement activation which would normally help the body to clear pathogens, highlights the relationship between COVID-19, aPL, and the risk for blood clots.
Given the heterogeneity of tests used to detect aPL and the limitations of aPL testing in sick patients, where false positive and negative aPL results can occur, or testing for aPL has been done only once, it is difficult to ascertain the clinical relevance of these aPL-positivity in COVID-19 patients.
Utilization of at least preventive dose anticoagulation (blood thinning medication) in hospitalized COVID-19 patients with positive aPL is important.
Preventative dose anticoagulation should be considered for non-hospitalized COVID-19 patients with known aPL-positivity (with or without APS; if not-receiving long-term anticoagulation), especially in the setting of additional risk factors for blood clots, for example, prolonged reduced mobility or high body mass index.
Full courses of COVID-19 vaccination, in accordance with national recommendations, are advised for all aPL positive patients with or without APS.

This published article also serves as a call and focus for clinical and basic scientific research.

————————————————–

PUBMED INFORMATION

Abstract

Coronavirus disease 2019 (COVID-19) is associated with a high rate of thrombosis. Prolonged activated partial thromboplastin times (aPTT) and antiphospholipid antibodies (aPL) are reported in COVID-19 patients. The majority of publications have not reported whether patients develop clinically relevant persistent aPL, and the clinical significance of new aPL-positivity in COVID-19 is currently unknown. However, the reports of aPL-positivity in COVID-19 raised the question whether common mechanisms exist in the pathogenesis of COVID-19 and antiphospholipid syndrome (APS). In both conditions, thrombotic microangiopathy resulting in microvascular injury and thrombosis is hypothesized to occur through multiple pathways, including endothelial damage, complement activation, and release of neutrophil extracellular traps (NETosis). APS-ACTION, an international APS research network, created a COVID-19 working group that reviewed common mechanisms, positive aPL tests in COVID-19 patients, and implications of COVID-19 infection for patients with known aPL positivity or APS, with the goals of proposing guidance for clinical management and monitoring of aPL-positive COVID-19 patients. This guidance also serves as a call and focus for clinical and basic scientific research.

————————————————–

OCTOBER 2021

apsaction aps Publications November 25, 2021December 12, 2023

Clinical and Laboratory Characteristics of Brazilian versus non-Brazilian Primary Antiphospholipid Syndrome Patients in APS ACTION Clinical Database and Repository.

de Azevedo Lopes E, Balbi GGM, Tektonidou MG, Pengo V, Sciascia S, Ugarte A, Belmont HM, Gerosa M, Fortin PR, Lopez-Pedrera C, Ji L, Cohen H, de Jesús GR, Branch DW, Nalli C, Petri M, Rodriguez E, Kello N, Ríos-Garcés R, Knight JS, Atsumi T, Willis R, Bertolaccini ML, Erkan D, and Andrade D on behalf of APS ACTION Investigators.

Adv Rheumatol. 2021;61(1):64.

————————————————–

ARTICLE SUMMARY FOR PATIENTS by the lead author, Dr. Gustavo Balbi

English Version:

Antiphospholipid syndrome (APS) is a very heterogeneous disease with different clinical presentations. Various factors may affect the presentation of the disease such as other cardiovascular disease risk factors (for example, hypertension, diabetes, or hyperlipidemia), association with lupus, or even the genetic profile of a patient.

In this APS ACTION registry analysis, we evaluated the clinical characteristics of Brazilian patients (one of the most miscegenated countries in the world), compared to patients from the other countries included in the registry. Our objective was to analyze if there were significant differences between the clinical characteristics of patients from different countries (focusing on the Brazilian population) in order to justify and guide a more detailed approach to the genetic determinants of APS in the future.

We included 415 patients diagnosed with primary APS (without other autoimmune diseases) in our analysis. Of those, 88 were from Brazil and 327 from other countries. We found that patients from Brazil were more likely to be female, non-white, obese, and sedentary. Regarding clinical manifestations, Brazilian patients presented more frequently with livedo (a skin condition that is frequent in APS patients), cognitive impairment, and seizures requiring treatment. Non-Brazilian patients more commonly had history of thrombocytopenia (low platelet counts) compared to Brazilian patients. The percentage of patients with blood clots were similar between groups.

The results of our study are important for the Brazilian patients who suffer from APS. Our study also sheds light on the relevance of studying the specific characteristics of the disease in different countries/genetic scenarios. Understanding those particular manifestations may help aid some of the unmet need for APS patients worldwide.

Portuguese Version – Versão em português

A Síndrome Antifosfolípide (SAF) é uma doença heterogênea que pode se manifestar de diversas formas. Diferentes fatores podem influenciar a maneira que a doença se expressa, como fatores de risco cardiovascular (por exemplo, hipertensão, diabetes, colesterol alto), a associação com lúpus e mesmo o perfil genético dos pacientes.

Nessa análise do registro do APS ACTION, nós realizamos um estudo que avaliou as características específicas dos pacientes brasileiros com SAF (que é um dos países com a população mais miscigenada do mundo), comparando-os com pacientes de outros países. O objetivo do trabalho foi verificar se existem diferenças entre os brasileiros e os pacientes de outros países (focando na população brasileira) de modo a justificar e guiar estudos mais detalhados sobre as caraterísticas genéticas na SAF no futuro.

Foram incluídos 415 pacientes com o diagnóstico de SAF primária (isto é, sem outras doenças autoimunes) na nossa análise. Deles, 88 eram brasileiros e 327 eram de outros países. Nós encontramos que os pacientes brasileiros eram mais frequentemente do sexo feminino, não-brancos, obesos e sedentários. Com relação às características clínicas, os brasileiros tiveram mais livedo (uma manifestação de pele frequente na SAF), distúrbio cognitivo e convulsões. Por outro lado, pacientes não brasileiros apresentaram plaquetopenia (plaquetas baixas) mais frequentemente que os brasileiros.

Os resultados do nosso estudo são importantes para os pacientes brasileiros que sofrem com a SAF. Além disso, ele chama atenção para a importância de se estudar características específicas da doença em diferentes países e condições genéticas. O entendimento dessas manifestações particulares em cada país pode auxiliar na resolução das necessidades não atendidas dos pacientes com SAF em todo o mundo.

————————————————–

PUBMED INFORMATION

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.

In exploring these findings further, it’s akin to uncovering the best penny slots to play in a vast casino—where lupus anticoagulant stands out as the key player amid various contenders.

————————————————–

DECEMBER 2020

apsaction aps Publications December 30, 2020November 25, 2021

Antiphospholipid Antibody Profile Stability Over Time: Prospective Results from APS ACTION Clinical Database and Repository.

Gkrouzman E, Sevim E, Finik J, Andrade D, Pengo V, Sciascia S, Tektonidou MG, Ugarte A, Chighizola CB, Belmont HM, Lopez-Pedrera C, Ji L, Fortin P, Efthymiou M, de Jesus GR, Branch DW, Nalli C, Petri M, Rodriguez E, Cervera R, Knight JS, Atsumi T, Willis R, Bertolaccini ML, Cohen H, Rand J, Erkan D on behalf of APS ACTION Investigators.

————————————————–

ARTICLE SUMMARY FOR PATIENTS by the lead author, Dr. Elena Gkrouzman

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by blood clots and pregnancy complications in patients with “persistently positive” antiphospholipid antibodies (aPL). “Persistently positive” is defined as positive aPL at two occasions at least 12 weeks apart based on the APS classification criteria.

Diagnosis of APS is confirmed by the measurement of aPL in the blood using one of the following tests: lupus anticoagulant (LA), anticardiolipin antibodies (aCL), and anti-β₂ glycoprotein-I antibodies (aβ₂GPI). The assessment of aPL profile (the combination of positive aPL tests as well as the levels of these tests) during evaluation of aPL-positive patients is critical. Persistently positive aPL are more likely to have important clinical implications, while transiently positive aPL, especially of low level may be a result of infections or medications. Certain aPL profiles, such as LA positivity, high titer aCL/aβ₂GPI, or triple-aPL positivity (LA, aCL, and aβ₂GPI), are strongly associated with aPL-related clinical events, although traditional risk factors also need to be taken into account while evaluating aPL-positive patients.

The course of aPL positivity (whether persistently positive aPL tests continue to remain positive in the long term) is important in the risk stratification and management of APS patients; however, there are limited prospective data on the course of aPL tests over time. The goal of this APS ACTION study was to better understand this course, along with its clinical and laboratory associations. For this purpose, an international cohort of patients with persistently positive aPL tests with or without APS was utilized (APS ACTION Registry).

Using data from 472 patients, it was determined that approximately 80% of our international cohort with clinically meaningful aPL profile at baseline (defined as positive LA test and/or aCL/aβ₂GPI IgG/M levels > 40 U) maintain such at an average follow-up of five years. Triple aPL-positivity at registry recruitment increased the chance of a stable, clinically meaningful aPL profile over time. Presence of another autoimmune disease such as lupus and use of medications such as hydroxychloroquine did not affect the chances of aPL profile stability. Moderate-to high levels (> 40 U) of aPL tests, positive LA, and two or more positive aPL tests at baseline were more likely to be associated with a stable, clinically meaningful aPL profile.

These results will guide future validation studies of aPL profiles in stored blood samples of patients in the APS ACTION Registry, bypassing issues of aPL test heterogeneity among different laboratories across the world, and interference of blood thinner use at time of LA testing. Stability of a clinically meaningful aPL profile over time may have further implications in the risk assessment for clinical events (blood clots or pregnancy complications), which will be studied in subsequent projects. Finally, this study may also inform frequency of aPL testing at follow up in clinical practice as certain aPL profiles are more likely to remain stable over time.

————————————————–

PUBMED INFORMATION

Abstract

Objective: APS ACTION Registry studies long-term outcomes in persistently antiphospholipid antibody (aPL)-positive patients. Our primary objective was to determine whether clinically meaningful aPL profiles at baseline remain stable over time. Our secondary objectives were to determine a) whether baseline characteristics differ between patients with stable and unstable aPL profiles, and b) predictors of unstable aPL profiles over time.

Methods: Clinically meaningful aPL profile was defined as positive lupus anticoagulant (LA) test and/or anticardiolipin (aCL)/anti-β² glycoprotein-I (aβ²GPI) IgG/M ≥40 U. Stable aPL profile was defined as a clinically meaningful aPL profile in at least two-thirds of follow-up measurements. Generalized linear mixed models with logit link were used for primary objective analysis.

Results: Of 472 patients with clinically meaningful aPL profile at baseline (median follow up: 5.1 years), 366/472 (78%) patients had stable aPL profiles over time, 54 (11%) unstable; and 52 (11%) inconclusive. Time did not significantly affect odds of maintaining a clinically meaningful aPL profile at follow-up in univariate (p=0.906) and multivariable analysis (p=0.790). Baseline triple aPL positivity decreased (Odds Ratio [OR] 0.25, 95% Confidence Interval [CI] 0.10-0.64, p=0.004) and isolated LA test positivity increased (OR 3.3, 95% CI 1.53-7.13, p=0.002) the odds of an unstable aPL profile over time.

Conclusion: Approximately 80% of our international cohort patients with clinically meaningful aPL profile at baseline maintain such at a median follow-up of five years; triple aPL-positivity increase the odds of a stable aPL profile. These results will guide future validation studies of stored blood samples through APS ACTION Core Laboratories.

————————————————–

← Previous