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1.
Int J Cardiol ; 331: 221-229, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33529654

RESUMO

BACKGROUND: Hughes-Stovin syndrome (HSS) is a systemic disease characterized by widespread vascular thrombosis and pulmonary vasculitis with serious morbidity and mortality. The HSS International Study Group is a multidisciplinary taskforce aiming to study HSS, in order to generate consensus recommendations regarding diagnosis and treatment. METHODS: We included 57 published cases of HSS (43 males) and collected data regarding: clinical presentation, associated complications, hemoptysis severity, laboratory and computed tomography pulmonary angiography (CTPA) findings, treatment modalities and cause of death. RESULTS: At initial presentation, DVT was observed in 29(33.3 %), thrombophlebitis in 3(5.3%), hemoptysis in 24(42.1%), and diplopia and seizures in 1 patient each. During the course of disease, DVT occurred in 48(84.2%) patients, and superficial thrombophlebitis was observed in 29(50.9%). Hemoptysis occurred in 53(93.0%) patients and was fatal in 12(21.1%). Pulmonary artery (PA) aneurysms (PAAs) were bilateral in 53(93%) patients. PAA were located within the main PA in 11(19.3%), lobar in 50(87.7%), interlobar in 13(22.8%) and segmental in 42(73.7%). Fatal outcomes were more common in patients with inferior vena cava thrombosis (p = 0.039) and ruptured PAAs (p < 0.001). Death was less common in patients treated with corticosteroids (p < 0.001), cyclophosphamide (p < 0.008), azathioprine (p < 0.008), combined immune modulators (p < 0.001). No patients had uveitis; 6(10.5%) had genital ulcers and 11(19.3%) had oral ulcers. CONCLUSIONS: HSS may lead to serious morbidity and mortality if left untreated. PAAs, adherent in-situ thrombosis and aneurysmal wall enhancement are characteristic CTPA signs of HSS pulmonary vasculitis. Combined immune modulators contribute to favorable outcomes.

2.
J Rheumatol ; 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-33259328

RESUMO

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-ß2 glycoprotein-I (aß2GPI) 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.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33253499

RESUMO

OBJECTIVES: An international multi-disciplinary initiative, jointly supported by American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR), is underway to develop new rigorous classification criteria to identify patients with high likelihood of Antiphospholipid Syndrome (APS) for research purposes. We applied an evidence- and consensus- based approach to identify candidate criteria and develop a hierarchical organization of criteria within domains. METHODS: During Phase I, the APS classification criteria Steering Committee used systematic literature reviews and surveys of international APS physician scientists to generate a comprehensive list of items related to APS. In Phase II, we reviewed the literature, administered surveys, formed domain subcommittees, and used Delphi exercises and nominal group technique to reduce potential APS candidate criteria. Candidate criteria were hierarchically organized into clinical and laboratory domains. RESULTS: Phase I generated 152 candidate criteria, expanded to 261 items with the addition of subgroups and candidate criteria with potential negative weights. Using iterative item reduction techniques in Phase II, we initially reduced these items to 64 potential candidate criteria organized into ten clinical and laboratory domains. Subsequent item reduction methods resulted in 27 candidate criteria, hierarchically organized into six additive domains (laboratory, macrovascular, microvascular, obstetric, cardiac, and hematologic) for APS classification. CONCLUSION: Using data- and consensus-driven methodology, we identified twenty-seven APS candidate criteria in six clinical or laboratory domains. In the next phase, the proposed candidate criteria will be used for real-world case collection and further refined, organized, and weighted to determine an aggregate score and threshold for APS classification.

4.
Pathobiology ; : 1-9, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33137805

RESUMO

We report a patient with severe Covid-19-associated coagulopathy and type 2 diabetes mellitus who tested positive for antiphospholipid antibodies (aPL). Analysis of skin specimens suggested direct SARS-CoV-2 viral-induced and complement-mediated vascular injury and thrombosis, consistent with prior reports. Serial aPL testing demonstrated high levels of anticardiolipin antibodies (aCL) that declined to insignificant levels over a period of 5 weeks. SARS-CoV-2 RNA was detected in nasopharyngeal swab specimens on serial assays performed over the same 5-week period, though it was not detected thereafter. We hypothesize that SARS-CoV-2 viral-induced aPL contributed to severe Covid-19-associated coagulopathy in this patient.

5.
Lupus ; 29(12): 1571-1593, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33100166

RESUMO

Antiphospholipid syndrome (APS), an acquired autoimmune thrombophilia, is characterised by thrombosis and/or pregnancy morbidity in association with persistent antiphospholipid antibodies. The 16th International Congress on Antiphospholipid Antibodies Task Force on APS Treatment Trends reviewed the current status with regard to existing and novel treatment trends for APS, which is the focus of this Task Force report. The report addresses current treatments and developments since the last report, on the use of direct oral anticoagulants in patients with APS, antiplatelet agents, adjunctive therapies (hydroxychloroquine, statins and vitamin D), targeted treatment including rituximab, belimumab, and anti-TNF agents, complement inhibition and drugs based on peptides of beta-2-glycoprotein I. In addition, the report summarises potential new players, including coenzyme Q10, adenosine receptor agonists and adenosine potentiation. In each case, the report provides recommendations for clinicians, based on the current state of the art, and suggests a clinical research agenda. The initiation and development of appropriate clinical studies requires a focus on devising suitable outcome measures, including a disease activity index, an optimal damage index, and a specific quality of life index.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32986935

RESUMO

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-ß2 -Glycoprotein-I [aß2 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 aß2 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.

8.
Lupus ; 29(12): 1594-1600, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32819183

RESUMO

The Task Force on Catastrophic Antiphospholipid Syndrome (CAPS) met again on occasion of the 16th International Congress on Antiphospholipid Antibodies (aPL) that was held in Manchester, England, in September 2019. Its aims were to assess the up-to-date knowledge on pathogenesis, clinical and laboratory features, diagnosis and classification, precipitating factors, and treatment of CAPS. This article summarizes the main aspects that were presented during the Task Force meeting at that Congress.

9.
Nat Rev Rheumatol ; 16(10): 581-589, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32733003

RESUMO

Reports of widespread thromboses and disseminated intravascular coagulation (DIC) in patients with coronavirus disease 19 (COVID-19) have been rapidly increasing in number. Key features of this disorder include a lack of bleeding risk, only mildly low platelet counts, elevated plasma fibrinogen levels, and detection of both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and complement components in regions of thrombotic microangiopathy (TMA). This disorder is not typical DIC. Rather, it might be more similar to complement-mediated TMA syndromes, which are well known to rheumatologists who care for patients with severe systemic lupus erythematosus or catastrophic antiphospholipid syndrome. This perspective has critical implications for treatment. Anticoagulation and antiviral agents are standard treatments for DIC but are gravely insufficient for any of the TMA disorders that involve disorders of complement. Mediators of TMA syndromes overlap with those released in cytokine storm, suggesting close connections between ineffective immune responses to SARS-CoV-2, severe pneumonia and life-threatening microangiopathy.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/complicações , Pneumonia Viral/complicações , Trombose/imunologia , Anticoagulantes/uso terapêutico , Antivirais/uso terapêutico , Proteínas do Sistema Complemento/imunologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Citocinas/imunologia , Coagulação Intravascular Disseminada/tratamento farmacológico , Coagulação Intravascular Disseminada/imunologia , Coagulação Intravascular Disseminada/patologia , Coagulação Intravascular Disseminada/virologia , Fibrinogênio/análise , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/uso terapêutico , Pandemias , Troca Plasmática/métodos , Contagem de Plaquetas/métodos , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Fatores de Risco , Trombose/tratamento farmacológico , Trombose/patologia , Trombose/virologia , Microangiopatias Trombóticas/tratamento farmacológico , Microangiopatias Trombóticas/imunologia , Microangiopatias Trombóticas/patologia , Microangiopatias Trombóticas/virologia
10.
Lupus ; : 961203320940776, 2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32703117

RESUMO

OBJECTIVE: This study aimed to use cluster analysis (CA) to identify different clinical phenotypes among antiphospholipid antibodies (aPL)-positive patients. METHODS: The Alliance for Clinical Trials and International Networking (APS ACTION) Registry includes persistently positive aPL of any isotype based on the Sydney antiphospholipid syndrome (APS) classification criteria. We performed CA on the baseline characteristics collected retrospectively at the time of the registry entry of the first 500 patients included in the registry. A total of 30 clinical data points were included in the primary CA to cover the broad spectrum of aPL-positive patients. RESULTS: A total of 497 patients from international centres were analysed, resulting in three main exclusive clusters: (a) female patients with no other autoimmune diseases but with venous thromboembolism (VTE) and triple-aPL positivity; (b) female patients with systemic lupus erythematosus, VTE, aPL nephropathy, thrombocytopaenia, haemolytic anaemia and a positive lupus anticoagulant test; and (c) older men with arterial thrombosis, heart valve disease, livedo, skin ulcers, neurological manifestations and cardiovascular disease (CVD) risk factors. CONCLUSIONS: Based on our hierarchical cluster analysis, we identified different clinical phenotypes of aPL-positive patients discriminated by aPL profile, lupus or CVD risk factors. Our results, while supporting the heterogeneity of aPL-positive patients, also provide a foundation to understand disease mechanisms, create new approaches for APS classification and ultimately develop new management approaches.

11.
J Thromb Haemost ; 18(9): 2274-2286, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32484606

RESUMO

BACKGROUND: Patients with antiphospholipid antibodies (aPL) and thromboembolism (TE) are at risk for recurrent TE. Few studies, however, distinguish patients based on the initial event. OBJECTIVES: We performed a systematic review and meta-analysis to investigate patients with aPL and venous TE (VTE), provoked or unprovoked, and patients with arterial TE (ATE). PATIENTS/METHODS: We conducted searches in PubMed, CINAHL, Cochrane, and EMBASE. Inclusion criteria were prospective trials or cohort studies investigating patients with aPL and ATE or VTE. Excluded studies did not provide estimated recurrence rates, did not specify whether the incident event was ATE or VTE, included patients with multiple events, or included <10 patients. Two-year summary proportions were estimated using a random effects model. RESULTS: Ten studies described patients with VTE, 2 with ATE, and 5 with VTE or ATE. The 2-year proportion for recurrent TE in patients with VTE who were taking anticoagulant therapy was 0.054 (95% confidence interval [CI], 0.037-0.079); the 2-year proportion for patients not taking anticoagulant therapy was 0.178 (95% CI, 0.150-0.209). Most studies did not distinguish whether VTE were provoked or unprovoked. The 2-year proportion for recurrent TE in patients with ATE who were taking anticoagulant therapy was 0.220 (95% CI, 0.149-0.311); the 2-year proportion for patients taking antiplatelet therapy was 0.216 (95% CI, 0.177-0.261). CONCLUSIONS: Patients with aPL and ATE may benefit from a different antithrombotic approach than patients with aPL and VTE. Prospective studies with well-defined cohorts with aPL and TE are necessary to determine optimal antithrombotic strategies.

13.
J Thromb Haemost ; 18(11): 2828-2839, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33462974

RESUMO

This guidance focuses on methodological aspects of lupus anticoagulant (LA) testing, as well as interpretation of results for clinicians. The main changes in how to test for LA compared with the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee 2009 guidelines, in the preanalytical phase are more detailed recommendations on how to handle testing in anticoagulated patients, and the timing of testing. Also, routine coagulation tests are advised to obtain more information on the coagulation background of the patient, and when necessary, anti-Xa activity measurement for heparins or specific assays for direct oral anticoagulants should be performed. The three-step procedure with two test systems (diluted Russell's viper venom time and activated partial thromboplastin time [aPTT]) is essentially not changed. Silica remains the preferable activator in the aPTT assays, but ellagic acid is not excluded. We advise simultaneous performance of the mixing and confirmatory step, in each sample with a prolonged screening test. The confirmatory step can also be performed on a mixture of patient plasma and normal pooled plasma. Cutoff values should be established in-house on at least 120 normals, with transference of the manufacturer's cutoffs as an alternative. Reporting of results has not been changed, although more attention is focused on what clinicians should know. Patient selection for LA testing has been expanded.

14.
Hematology Am Soc Hematol Educ Program ; 2019(1): 426-432, 2019 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-31808842

RESUMO

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by thrombosis, pregnancy morbidity, or nonthrombotic manifestations in patients with persistently positive antiphospholipid antibodies (aPL). Conventional APS treatment focuses on antithrombotic strategies, which are usually ineffective for the microvascular and nonthrombotic manifestations of aPL. Using a case-based presentation, this review focuses on the role of immunosuppression in nonobstetric APS, including B-cell inhibition (rituximab, belimumab, and bortezomib), complement inhibition (eculizumab), mechanistic target of rapamycin inhibition (sirolimus), vascular endothelial cell modulation (defibrotide), statins, and traditional rheumatologic disease-modifying agents (hydroxychloroquine, mycophenolate mofetil, azathioprine, and cyclophosphamide).


Assuntos
Síndrome Antifosfolipídica/tratamento farmacológico , Imunossupressão , Imunossupressores/uso terapêutico , Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/imunologia , Síndrome Antifosfolipídica/patologia , Humanos , Masculino , Pessoa de Meia-Idade
15.
Eur J Rheumatol ; 6(4): 207-211, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31657703

RESUMO

OBJECTIVE: iBook on Antiphospholipid Syndrome (APS) did not exist before our work, and hence the utility of an Apple iBook as a teaching method in APS for medical students has never been assessed. Our objective was to evaluate medical students' improvement of knowledge and satisfaction with an interactive APS iBook, in comparison with conventional teaching methods. METHODS: An iBook designer with the guidance of a medical team developed the APS iBook in both French and English. Second-year medical students, naïve of APS knowledge, were enrolled from two institutions. For the "teaching intervention", participants were randomly assigned to three groups: a) APS iBook with interactive capability; b) printed copy of the APS iBook material; and c) classroom lecture presentation of the APS iBook material by a physician-scientist experienced in APS. The participants filled a standardized medical questionnaire about APS before and after teaching interventions to determine the relative change of knowledge. Participants were asked to fill out a standardized satisfaction survey. After 20 weeks of the intervention, recall capability of students was tested. RESULTS: A total of 233 second-year medical students were enrolled (iBook group: 73; print group: 79, and lecture group: 81). Relative change of knowledge was not different between the iBook group and the printed material group; additionally, it was significantly higher in the lecture group than the two other methods. Satisfaction was significantly higher in both the lecture and the iBook groups than the print group, on several dimensions including overall quantitative satisfaction, subjective enhanced knowledge, interactivity, quality of content, comprehensibility, and pleasure of learning. Recall capability of students (n=109, 47%) was not significantly different among groups. CONCLUSION: The APS iBook is as effective as printed material in improving medical student's knowledge, although a classroom lecture was the most effective method when compared to self-learning methods. Among self-learning methods, medical students are more satisfied with the APS iBook, whereas the recall capability was not different among groups. These results suggest that the APS iBook will help medical students in their curriculum and increase the awareness of APS among the community.

16.
Curr Rheumatol Rep ; 21(10): 56, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31493005

RESUMO

PURPOSE OF REVIEW: Diffuse alveolar hemorrhage (DAH) is a rare but devastating manifestation of antiphospholipid syndrome (APS) patients with or without other systemic autoimmune diseases. Data regarding diagnosis and treatment are limited to case series. We review diagnostic and therapeutic strategies employed in APS patients with DAH and discuss our experience in managing these complex patients. RECENT FINDINGS: Pulmonary capillaritis likely contributes to the pathogenesis, however is only observed in half of the biopsies. Corticosteroids induce remission in the majority of patients, however almost half recur and require a steroid-sparing immunosuppressive to maintain remission. Cyclophosphamide- or rituximab-based regimens achieve the highest remission rates (50%); other strategies include intravenous immunoglobulin, plasmapheresis, mycophenolate mofetil, and/or azathioprine. Given the rarity of DAH in APS, treatment is guided by interdisciplinary experience. Why certain patients achieve full remission with corticosteroids while others require immunosuppressive agents is unknown; future research should focus on the pathophysiology and optimal management.


Assuntos
Síndrome Antifosfolipídica/complicações , Hemorragia/etiologia , Pneumopatias/etiologia , Síndrome Antifosfolipídica/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Hemorragia/tratamento farmacológico , Humanos , Imunossupressores/uso terapêutico , Pneumopatias/tratamento farmacológico , Alvéolos Pulmonares , Rituximab/uso terapêutico
17.
Autoimmun Rev ; 18(11): 102395, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31520800

RESUMO

BACKGROUND: According to criteria for the classification of Systemic Lupus Erythematosus (SLE), thrombocytopenia is one of the disease-defining hematologic disorders. Since the recognition of Antiphospholipid Syndrome (APS), thrombocytopenia was frequently reported but several studies yielded contradictory results on the association between aPL-positivity and thrombocytopenia. METHODS: We evaluated the role of antiphospholipid antibodies (aPL) and different aPL profiles on the risk of thrombocytopenia in SLE patients by conducting a systematic review and meta-analysis of available literature from 1987 to 2018. MEDLINE, EMBASE, Cochrane Library, congress abstracts, and reference lists of eligible studies were searched. Studies were selected if they included SLE patients with descriptions of the exposure to aPL and the outcomes (thrombocytopenia). Two reviewers extracted study characteristics and outcome data from published reports. Estimates were pooled using random effects models and sensitivity analyses. We followed the PRISMA guidelines for all stages of the meta-analysis. PROSPERO registration number: CRD42015027378. RESULTS: From 3278 articles identified, 53 studies met inclusion criteria amounting to 9019 SLE patients. Twenty-nine percent of aPL-positive SLE patients had thrombocytopenia compared to 15.1% in aPL-negative SLE patients. The overall pooled Odds Ratio (OR) for thrombocytopenia in aPL positive patients was 2.48 (95% CI; 2.10-2.93). Among aPL subtypes, the risk of thrombocytopenia was highest for lupus anticoagulant (OR = 3.56 [95% CI, 2.57-5.25]), IgM anti-ß2-GP1(OR = 2.87 [95% CI; 2.57-5.25]), IgG and IgM anticardiolipin antibodies (OR = 1.87 [95% CI; 1.52-2.31] and OR = 1.73 [95% CI; 1.36-2.19] respectively). CONCLUSIONS: The occurrence of thrombocytopenia was strongly determined by various aPL profiles in SLE patients. While the association between IgM antibodies and other APS manifestations including thrombosis is debated, IgM isotypes are helpful in the risk stratification of thrombocytopenia in SLE.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Lúpus Eritematoso Sistêmico/epidemiologia , Trombocitopenia/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Estudos Transversais , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Fatores de Risco , Trombocitopenia/imunologia
18.
J Thromb Haemost ; 17(12): 2069-2080, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31364274

RESUMO

BACKGROUND: Variability remains a challenge in lupus anticoagulant (LA) testing. OBJECTIVE: To validate LA test performance between Antiphospholipid Syndrome Alliance for Clinical Trials and International Networking (APS ACTION) Core laboratories and examine agreement in LA status between Core and local/hospital laboratories contributing patients to this prospective registry. METHODS: Five Core laboratories used the same reagents, analyzer type, protocols, and characterized samples for LA validation. Non-anticoagulated registry samples were retested at the corresponding regional Core laboratories and anticoagulated samples at a single Core laboratory. Categorical agreement and discrepancies in LA status between Core and local/hospital laboratories were analyzed. RESULTS: Clotting times for the reference/characterized plasmas used for normalized ratios were similar between Core laboratories (CV <4%); precision and agreement for LA positive/negative plasma were similar (all CV ≤5%) in the four laboratories that completed both parts of the validation exercise; 418 registry samples underwent LA testing. Agreement for LA positive/negative status between Core and local/hospital laboratories was observed in 87% (115/132) non-anticoagulated and 77% (183/237) anticoagulated samples. However, 28.7% (120/418) of samples showed discordance between the Core and local/hospital laboratories or equivocal LA results. Some of the results of the local/hospital laboratories might have been unreliable in 24.7% (41/166) and 23% (58/252) of the total non-anticoagulated and anticoagulated samples, respectively. Equivocal results by the Core laboratory might have also contributed to discordance. CONCLUSIONS: Laboratories can achieve good agreement in LA performance by use of the same reagents, analyzer type, and protocols. The standardized Core laboratory results underpin accurate interpretation of APS ACTION clinical data.


Assuntos
Síndrome Antifosfolipídica/diagnóstico , Ensaio de Proficiência Laboratorial , Inibidor de Coagulação do Lúpus/sangue , Testes Sorológicos/normas , Anticoagulantes/sangue , Síndrome Antifosfolipídica/sangue , Biomarcadores/sangue , Ensaios Clínicos como Assunto , Bases de Dados Factuais , Humanos , Variações Dependentes do Observador , Valor Preditivo dos Testes , Estudos Prospectivos , Tempo de Protrombina/normas , Sistema de Registros , Reprodutibilidade dos Testes
19.
Semin Arthritis Rheum ; 49(3): 464-468, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31153708

RESUMO

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-ß2 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 ±â€¯3.3 vs. 6 ±â€¯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 ±â€¯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.


Assuntos
Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/diagnóstico , Sistema de Registros , Medição de Risco/métodos , Trombose/etiologia , Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/complicações , Biomarcadores/sangue , Estudos Transversais , Feminino , Seguimentos , Saúde Global , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Trombose/sangue , Trombose/epidemiologia
20.
Cell Host Microbe ; 26(1): 100-113.e8, 2019 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-31227334

RESUMO

Given the immense antigenic load present in the microbiome, we hypothesized that microbiota mimotopes can be a persistent trigger in human autoimmunity via cross-reactivity. Using antiphospholipid syndrome (APS) as a model, we demonstrate cross-reactivity between non-orthologous mimotopes expressed by a common human gut commensal, Roseburia intestinalis (R. int), and T and B cell autoepitopes in the APS autoantigen ß2-glycoprotein I (ß2GPI). Autoantigen-reactive CD4+ memory T cell clones and an APS-derived, pathogenic monoclonal antibody cross-reacted with R. int mimotopes. Core-sequence-dependent anti-R. int mimotope IgG titers were significantly elevated in APS patients and correlated with anti-ß2GPI IgG autoantibodies. R. int immunization of mice induced ß2GPI-specific lymphocytes and autoantibodies. Oral gavage of susceptible mice with R. int induced anti-human ß2GPI autoantibodies and autoimmune pathologies. Together, these data support a role for non-orthologous commensal-host cross-reactivity in the development and persistence of autoimmunity in APS, which may apply more broadly to human autoimmune disease.


Assuntos
Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Autoimunidade , Linfócitos B/imunologia , Clostridiales/imunologia , Reações Cruzadas , Linfócitos T/imunologia , Adulto , Idoso , Animais , Síndrome Antifosfolipídica/patologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Feminino , Trato Gastrointestinal/microbiologia , Humanos , Imunoglobulina G/sangue , Masculino , Camundongos , Pessoa de Meia-Idade , Modelos Animais , Adulto Jovem , beta 2-Glicoproteína I/imunologia
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