Characteristics of Antiphospholipid Antibody Positive Patients in AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking

OBJECTIVE: To describe baseline characteristics of antiphospholipid antibody (aPL)-positive patients, overall and by clinical and laboratory subtypes, enrolled in an international registry. METHODS: AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking Registry includes persistently aPL-positive adults. We evaluated baseline sociodemographic and aPL-related (APS classification criteria and "non-criteria") characteristics of patients overall and in subgroups (aPL-positive without APS, APS overall, thrombotic APS [TAPS] only, obstetric APS [OAPS] only, and both TAPS/OAPS). We assessed baseline characteristics of patients tested for three aPL (lupus anticoagulant test [LA], anticardiolipin antibody [aCL], and anti-β2 -Glycoprotein-I [aβ2 GPI]) by aPL profiles (LA only, single, double, and triple aPL positivity). RESULTS: Of 804 aPL-positive patients (mean age: 45 ± 13y; female: 74%; white 68%; other systemic autoimmune diseases: 36%), 80% were classified as APS (55% TAPS, 9% OAPS, and 15% TAPS/OAPS). In the overall cohort, 71% had vascular thrombosis, 50% with pregnancy history had obstetric morbidity, and 56% had at least one non-criteria manifestation. Among those with three aPL tested (n: 660), 42% were triple aPL positive. While single, double and triple aPL positive subgroups had similar frequencies of vascular, obstetric, and non-criteria events, these events were lowest in the single aPL subgroup consisting of aCL or aβ2 GPI only. CONCLUSION: Our study demonstrates the heterogeneity of aPL-related clinical manifestations and laboratory profiles in a multicenter, international cohort. Within single aPL-positivity, LA may be a major contributor to clinical events. Future prospective analyses, using standardized core laboratory aPL tests, will help clarify aPL risk profiles and improve risk stratification

The adjusted global antiphospholipid syndrome score (aGAPSS) and the risk of recurrent thrombosis: Results from the APS ACTION cohort

Objectives: To assess whether patients with antiphospholipid syndrome (APS) and history of recurrent thrombosis have higher levels of adjusted Global AntiphosPholipid Syndrome Score (aGAPSS) when compared to patients without recurrent thrombosis. Methods: In this cross-sectional study of antiphospholipid antibody (aPL)-positive patients, we identified APS patients with a history of documented thrombosis from the AntiPhospholipid Syndrome Alliance For Clinical Trials and InternatiOnal Networking (APS ACTION) Clinical Database and Repository (“Registry”). Data on aPL-related medical history and cardiovascular risk factors were retrospectively collected. The aGAPSS was calculated at Registry entry by adding the points corresponding to the risk factors: three for hyperlipidemia, one for arterial hypertension, five for positive anticardiolipin antibodies, four for positive anti-β2 glycoprotein-I antibodies and four for positive lupus anticoagulant test. Results: The analysis included 379 APS patients who presented with arterial and/or venous thrombosis. Overall, significantly higher aGAPSS were seen in patients with recurrent thrombosis (arterial or venous) compared to those without recurrence (7.8 ± 3.3 vs. 6 ± 3.9, p<0.05). When analyzed based on the site of the recurrence, patients with recurrent arterial, but not venous, thrombosis had higher aGAPSS (8.1 ± SD 2.9 vs. 6 ± 3.9; p<0.05). Conclusions: Based on analysis of our international large-scale Registry of aPL-positive patients, the aGAPSS might help risk stratifying patients based on the likelihood of developing recurrent thrombosis in APS

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

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

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').

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. 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. Of the 55 first pregnancies observed after registry recruitment among nulliparous and multiparous participants, 15 (27%) resulted in early pregnancy loss 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

The comparison of real world and core laboratory antiphospholipid antibody ELISA results from antiphospholipid syndrome alliance for clinical trials &amp; international networking (APS ACTION) clinical database and repository analysis

Background: The APS ACTION International Clinical Database and Repository includes a secure web-based data capture system storing patient information including demographics, antiphospholipid antibodies (aPL)-related medical history, and aPL tests. Despite efforts at harmonization, inter-assay variability remains a problem in aPL testing. As a clinical repository open to researchers, ensuring comparability between assays and consistency in results between APS ACTION laboratories is essential to the validity of studies emerging from this network. Objective: To assess the level of agreement between an aPL-registry inclusion and core laboratory (core lab) anticardiolipin antibody (aCL) and anti-β 2 -glycoprotein-I antibody (aβ 2 GPI) ELISA testing results. Methods: Patients are recruited from 25 international centers based on positive aPL tests at inclusion. All samples are retested at the corresponding national APS ACTION core lab to confirm aPL positivity based on standard validated protocols. We analysed the categorical agreement, degree of linear association, and correlation between inclusion (local laboratory) and core lab aPL tests. Samples were included in this study only if results of aPL testing with ELISA at baseline were available. Results: 497 registry samples underwent confirmatory aPL tests. Categorical agreement between the inclusion and core lab values, as expressed by Cohen&apos;s kappa coefficients, ranged between 0.61 and 0.80 (as substantial agreement). The correlation between quantitative results in the aCL and aβ 2 GPI was better for IgM and IgA compared to IgG (Spearman rho 0.789 and 0.666 vs. 0.600 for aCL and rho 0.892 and 0.744 vs. 0.432 for aβ 2 GPI). Conclusions: The results of inclusion for aCL and aβ 2 GPI tests used for recruitment into the registry were in agreement to the results obtained by the APS ACTION core laboratories; aCL and aβ 2 GPI results showed very good categorical agreement. This agreement increased when considering high titer (&amp;gt;40 units) samples. APS ACTION is a reliable and useful research resource for APS. © 2019 Elsevier Lt

The comparison of real world and core laboratory antiphospholipid antibody ELISA results from antiphospholipid syndrome alliance for clinical trials & international networking (APS ACTION) clinical database and repository analysis

BACKGROUND: The APS ACTION International Clinical Database and Repository includes a secure web-based data capture system storing patient information including demographics, antiphospholipid antibodies (aPL)-related medical history, and aPL tests. Despite efforts at harmonization, inter-assay variability remains a problem in aPL testing. As a clinical repository open to researchers, ensuring comparability between assays and consistency in results between APS ACTION laboratories is essential to the validity of studies emerging from this network. OBJECTIVE: To assess the level of agreement between an aPL-registry inclusion and core laboratory (core lab) anticardiolipin antibody (aCL) and anti-β2-glycoprotein-I antibody (aβ2GPI) ELISA testing results. METHODS: Patients are recruited from 25 international centers based on positive aPL tests at inclusion. All samples are retested at the corresponding national APS ACTION core lab to confirm aPL positivity based on standard validated protocols. We analysed the categorical agreement, degree of linear association, and correlation between inclusion (local laboratory) and core lab aPL tests. Samples were included in this study only if results of aPL testing with ELISA at baseline were available. RESULTS: 497 registry samples underwent confirmatory aPL tests. Categorical agreement between the inclusion and core lab values, as expressed by Cohen's kappa coefficients, ranged between 0.61 and 0.80 (as substantial agreement). The correlation between quantitative results in the aCL and aβ2GPI was better for IgM and IgA compared to IgG (Spearman rho 0.789 and 0.666 vs. 0.600 for aCL and rho 0.892 and 0.744 vs. 0.432 for aβ2GPI). CONCLUSIONS: The results of inclusion for aCL and aβ2GPI tests used for recruitment into the registry were in agreement to the results obtained by the APS ACTION core laboratories; aCL and aβ2GPI results showed very good categorical agreement. This agreement increased when considering high titer (>40 units) samples. APS ACTION is a reliable and useful research resource for APS

Factors associated with first thrombosis in patients presenting with obstetric antiphospholipid syndrome (APS) in the APS Alliance for Clinical Trials and International Networking Clinical Database and Repository: a retrospective study

Objective: To evaluate the subsequent rate of thrombosis among women with obstetric antiphospholipid syndrome (Ob-APS) in a multicentre database of antiphospholipid antibody (aPL)-positive patients, and the clinical utility of the adjusted Global Antiphospholipid Syndrome Score (aGAPSS), a validated tool to assess the likelihood of developing new thrombosis, in this group of patients. Design: Retrospective study. Setting: The Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking Clinical Database and Repository. Population: Women with Ob-APS. Methods: Comparison of clinical and laboratory characteristics and measurement of aGAPSS in women with Ob-APS, with or without thrombosis, after initial pregnancy morbidity (PM). Main outcome measures: Risk factors for thrombosis and aGAPSS. Results: Of 550 patients, 126 had Ob-APS; 74/126 (59%) presented with thrombosis, and 47 (63%) of these women developed thrombosis after initial PM, in a mean time of 7.6 ± 8.2 years (4.9/100 patient years). Younger age at diagnosis of Ob-APS, additional cardiovascular risk factors, superficial vein thrombosis, heart valve disease, and multiple aPL positivity increased the risk of first thrombosis after PM. Women with thrombosis after PM had a higher aGAPSS compared with women with Ob-APS alone [median 11.5 (4–16) versus 9 (4–13); P = 0.0089]. Conclusion: Based on a retrospective analysis of our multicentre aPL database, 63% of women with Ob-APS developed thrombosis after initial obstetric morbidity; additional thrombosis risk factors, selected clinical manifestations, and high-risk aPL profile increased the risk. Women with subsequent thrombosis after Ob-APS had a higher aGAPSS at entry to the registry. We believe that aGAPSS is a valid tool to improve risk stratification in aPL-positive women. Tweetable abstract: More than 60% of women with obstetric antiphospholipid syndrome had thrombosis after initial pregnancy morbidity. © 2018 Royal College of Obstetricians and Gynaecologist

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

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 (aCL) and anti-β2 glycoprotein-I antibodies (aβ2GPI), and with aPL persistence. Given that the three aPL tests detect partially overlapping sets of antibodies, the primary goal of this study was to characterize the associations among aPL tests using 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 Spearman's rank correlation with Bonferroni adjusted significance level for multiple comparisons. An aPL Load was calculated based on six tests (aCL IgG/M/A and aβ2GPI IgG/M/A); a receiver operating characteristic (ROC) 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 units) titers of aCL and aβ2GPI IgG/M/A was higher in patients who were positive for LA versus negative. An aPL Load was calculated for each patient to assess their overall aPL burden. For every one-point increase in aPL Load, the possibility of a positive LA test increased by 32% (OR 1.32, 95% CI 1.2, 1.5, p<.001). Based on Core Laboratory data from a large international registry, most aPL ELISA ≥40U and a high calculated aPL Load combining six aPL ELISAs 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

DJ: ¿Un Nuevo Periodismo?

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