RESUMO
Antiphospholipid antibodies (aPL) are a family of autoantibodies targeting phospholipid-binding proteins and are associated with several clinical settings, and most notably define the antiphospholipid syndrome (APS). These antibodies can be identified using a variety of laboratory tests, which include both solid-phase immunological assays and functional clotting assays that detect lupus anticoagulants (LA). aPLs are linked to a range of adverse medical conditions, such as thrombosis and complications affecting the placenta and fetus, potentially leading to morbidity and mortality. The specific aPL identified, along with the pattern of reactivity, correlates with the severity of these conditions. Therefore, laboratory testing for aPL is crucial for evaluating the risk of complications and for fulfilling certain classification criteria for APS, which are also applied as diagnostic markers in medical practice. This review provides an overview of the available laboratory tests currently for measuring aPL and discusses their clinical implications.
Assuntos
Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica , Humanos , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/imunologia , Síndrome Antifosfolipídica/sangue , Anticorpos Antifosfolipídeos/sangue , Gravidez , Feminino , Inibidor de Coagulação do Lúpus/sangue , Biomarcadores/sangueRESUMO
Antiphospholipid syndrome (APS) is an acquired multisystem autoimmune disease characterized clinically by vascular thrombotic events, or pregnancy complications or nonthrombotic manifestations in the presence of persistently elevated antiphospholipid antibodies (aPL). We highlighted our case, which fulfills both the old APS classification criteria (1999,2006) _and the newest one (2023). The latest demonstrates very high specificity (99%) for APS diagnosis, compared to the older revised Sapporo criteria (86%). According to the new recommendation, the criteria are classified into 6 clinical and 2 laboratory domains, patient must accumulate at least 3 points from each clinical and laboratory domains. Our patient was diagnosed with antiphospholipid syndrome in 2018, as she had transient ischemic attack (TIA) without any changes on magnetic resonance tomography (MRI), and laboratory tests revealed triple positive antiphospholipid antibodies (12 points). Additional diagnostic tests were performed_thrombocytopenia, aortic valve thickening was noteworthy (4 points). Thus, TIA which had similar strength to stroke as the manifestation of arterial thrombosis by old guidelines, it is rejected according to the new recommendation, so the patient lost minimum 2 points; On the other hand, the current criteria added nonthrombotic events as weighted clinical domains, which gave the points to our patient. In conclusion we fully and highly specifically confirmed APS diagnosis as ACR/EULAR suggests.
Assuntos
Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica , Ataque Isquêmico Transitório , Humanos , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/diagnóstico por imagem , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/imunologia , Feminino , Anticorpos Antifosfolipídeos/sangue , Anticorpos Antifosfolipídeos/imunologia , Ataque Isquêmico Transitório/diagnóstico por imagem , Ataque Isquêmico Transitório/diagnóstico , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , AdultoAssuntos
Síndrome Antifosfolipídica , Endotélio Vascular , Humanos , Síndrome Antifosfolipídica/sangue , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Endotélio Vascular/efeitos dos fármacos , Feminino , Microvasos/metabolismo , Microvasos/efeitos dos fármacos , Microvasos/patologia , Microvasos/fisiopatologia , Microvasos/imunologia , Masculino , Adulto , Anticorpos Antifosfolipídeos/sangue , Veias , Pessoa de Meia-IdadeRESUMO
OBJECTIVES: Severe thrombotic antiphospholipid syndrome (APS) frequently affects the kidney, heart, and central nervous system. The precise frequency, clinical picture, differential diagnoses, and outcome of APS-related hematological involvement are lacking, especially in patients requiring ICU admission. This study aimed to describe the hematological manifestations associated with critically ill thrombotic APS patients and catastrophic antiphospholipid syndrome. METHODS: This French, national, multicenter, retrospective study, conducted, from January 2000 to September 2018, included all APS patients admitted to 24 participating centers' ICUs with any new thrombotic manifestation. The prevalence of hematological manifestations and their associated outcomes were studied. RESULTS: One hundred and thirty-four patients, female 72%, median [IQR] age 45 [34-56] years, with 152 episodes were included. Anemia was present in 95% of episodes and thrombocytopenia in 93%. The lowest values for hemoglobin and platelets were 7.1 [6.3-8.8] g/dL and 38 [21-60] g/L, respectively. The lowest platelet count below 20 g/L was significantly associated with a higher in-ICU mortality rate (50%, p < 0.0001). A thrombotic microangiopathy syndrome (TMA) syndrome was seen in 16 patients (12%) and was associated with higher in-hospital mortality (p = 0.05). Median ADAMTS-13 levels were 44% [27-74]. Anti-ADAMTS13 antibodies were tested in 11 patients and found negative in all. A suspicion of heparin-induced thrombocytopenia (HIT) was raised in 66 patients but only four patients were classified as definite HIT. Disseminated intravascular coagulation (DIC) was seen in 51% of patients. CONCLUSION: Thrombocytopenia is very frequent in severe APS patients and may be related to TMA, HIT, or DIC. Deciphering the mechanisms of thrombocytopenia is decisive in CAPS patients. Key Points ⢠Thrombocytopenia is the hallmark laboratory finding in CAPS. ⢠A complete thrombotic microangiopathy pattern is infrequent in CAPS patients. ⢠Alternate diagnoses of CAPS, especially heparin-induced thrombocytopenia, need to be adequately investigated.
Assuntos
Síndrome Antifosfolipídica , Estado Terminal , Trombocitopenia , Microangiopatias Trombóticas , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/sangue , Estudos Retrospectivos , Adulto , Trombocitopenia/complicações , Trombocitopenia/sangue , Microangiopatias Trombóticas/sangue , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/complicações , Trombose/etiologia , Unidades de Terapia Intensiva , França/epidemiologia , Mortalidade Hospitalar , Anemia/sangue , Anemia/complicações , Anemia/etiologia , Proteína ADAMTS13/sangue , Contagem de PlaquetasRESUMO
BACKGROUND: Diagnosing Antiphospholipid Syndrome (APS) relies heavily on laboratory findings, particularly the detection of specific antibodies like lupus anticoagulant (LA), IgG and/or IgM anti-cardiolipin (aCL), and IgG and/or IgM anti-ß2 glycoprotein 1 (aB2GP1). Although ELISA is widely used in the US for this purpose, standardization between different assay methodologies remains challenging, leading to significant variability across laboratories. Particle-based multi-analyte technology (PMAT) offers a streamlined one-step detection for all six antiphospholipid (aPL) autoantibodies, covering aCL and aB2GP1 of IgA, IgG, and IgM isotypes. METHODS: In this study involving 224 subjects, including 34 clinically diagnosed with APS, alongside 160 non-APS patients and 30 healthy donors, PMAT's performance was evaluated against commercial ELISA in detecting aPL antibodies. RESULTS: At the manufacturer's suggested cutoff, PMAT exhibited sensitivity comparable to ELISA, albeit with a low to moderate decrease in specificity for certain antibodies. With anti-CL IgM alone, PMAT displayed a 17.7% decrease in sensitivity, accompanied by a corresponding 31.1% increase in specificity compared to ELISA. However, applying a stricter cutoff (88-90% specificity), IgA and IgM antibodies yielded 5.9-17.6% higher sensitivities with PMAT, and IgG antibodies displayed similar sensitivity. CONCLUSIONS: In this study cohort, PMAT demonstrated higher or comparable sensitivity to that of commercial ELISA for all six aPL antibodies at a specificity cutoff near 90%. Notably, PMAT demonstrated superior sensitivity and specificity overall in detecting IgA aCL and aB2GP1 antibodies. This study highlights the potential of automated PMAT for detecting aPL antibodies in APS evaluation.
Assuntos
Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica , Ensaio de Imunoadsorção Enzimática , Humanos , Ensaio de Imunoadsorção Enzimática/métodos , Anticorpos Antifosfolipídeos/sangue , Anticorpos Antifosfolipídeos/imunologia , Anticorpos Antifosfolipídeos/análise , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/imunologia , Síndrome Antifosfolipídica/sangue , Feminino , Masculino , AdultoAssuntos
Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica , Reumatologia , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/imunologia , Síndrome Antifosfolipídica/classificação , Humanos , Anticorpos Antifosfolipídeos/sangue , Reumatologia/normas , Reumatologia/métodos , Europa (Continente) , Estados Unidos , Sociedades Médicas , Reprodutibilidade dos TestesAssuntos
Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/imunologia , Síndrome Antifosfolipídica/classificação , Humanos , Anticorpos Antifosfolipídeos/sangue , Reprodutibilidade dos TestesRESUMO
Antiphospholipid syndrome (APS) is a rare systemic autoimmune disease characterized by recurrent pregnancy morbidity or thrombosis in combination with the persistent presence of antiphospholipid antibodies (aPLs) in plasma/serum. Antiphospholipid antibodies are a heterogeneous, overlapping group of autoantibodies, of which anti-ß2-glycoprotein I (aß2GPI), anticardiolipin (aCL) antibodies and antibodies that prolong plasma clotting time in tests in vitro known as lupus anticoagulant (LAC) are included in the laboratory criteria for the diagnosis of APS. The presence of LAC antibodies in plasma is indirectly determined by measuring the length of coagulation in two tests - activated partial thromboplastin time (aPTT) and diluted Russell's viper venom time (dRVVT). The concentration of aß2GPI and aCL (immunglobulin G (IgG) and immunoglobulin M (IgM) isotypes) in serum is directly determined by solid-phase immunoassays, either by enzyme-linked immunosorbent assay (ELISA), fluoroimmunoassay (FIA), immunochemiluminescence (CLIA) or multiplex flow immunoassay (MFIA). For patient safety, it is extremely important to control all three phases of laboratory testing, i.e. preanalytical, analytical and postanalytical phase. Specialists in laboratory medicine must be aware of interferences in all three phases of laboratory testing, in order to minimize these interferences. The aim of this review was to show the current pathophysiological aspects of APS, the importance of determining aPLs-a in plasma/serum, with an emphasis on possible interferences that should be taken into account when interpreting laboratory findings.
Assuntos
Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica , Humanos , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/imunologia , Anticorpos Antifosfolipídeos/sangue , Feminino , Gravidez , Anticorpos Anticardiolipina/sangue , Inibidor de Coagulação do Lúpus/sangue , Ensaio de Imunoadsorção EnzimáticaRESUMO
The relationship between antiphospholipid syndrome (APS) and acute viral infection, such as SARS-CoV-2, is unclear. This study aims to assess symptoms, antiphospholipid antibody (aPL) fluctuations, and complication risks in APS patients infected with SARS-CoV-2. APS patients from Peking Union Medical College Hospital during the COVID-19 outbreak (October-December 2022) were included. Age- and gender-matched APS patients without infection served as controls. Data on demographics, symptoms, treatments, and serum aPL levels were analyzed. Of 234 APS patients, 107 (45.7%) were infected with SARS-CoV-2. Typical symptoms included high fever (81.3%), cough/expectoration (70.1%), and pharyngalgia (52.3%). Age- and gender-based matching selected 97 patients in either infected or uninfected group. After infection, anti-ß-2-glycoprotein I-IgG (aß2GP1-IgG) increased from 4.14 to 4.18 AU/ml, aß2GP1-IgM decreased from 9.85 to 7.38 AU/ml, and anticardiolipin-IgA (aCL-IgA) significantly increased with a median remaining at 2.50 APLU/ml. Lupus anticoagulants and other aPLs remained stable. Arterial thrombosis incidence increased from 18 (18.6%) to 21 (21.6%), while venous thrombosis incidence did not change. Additionally, 7 (6.5%) patients presented either new-onset or worsening thrombocytopenia, characterized by a significant decline in platelet count (no less than 10 × 109/L) within two weeks of SARS-CoV-2 infection, all of which recovered within 2 weeks. Acute SARS-CoV-2 infection may induce or worsen thrombocytopenia but does not substantially increase thrombotic events in APS. The process of SARS-CoV-2 infection was related to mild titer fluctuation of aß2GP1-IgG, aß2GP1-IgM and aCL-IgA in APS patients, necessitating careful monitoring and management.
Assuntos
Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/imunologia , Masculino , Feminino , Síndrome Antifosfolipídica/imunologia , Síndrome Antifosfolipídica/sangue , Adulto , Pessoa de Meia-Idade , Anticorpos Antifosfolipídeos/sangue , SARS-CoV-2/imunologia , China/epidemiologia , Anticorpos Anticardiolipina/sangue , beta 2-Glicoproteína I/imunologia , Imunoglobulina G/sangue , IdosoRESUMO
The heterogeneity of the T cell receptor (TCR) repertoire critically influences the autoimmune response in obstetric antiphospholipid syndrome (OAPS) and is intimately associated with the prophylaxis of autoimmune disorders. Investigating the TCR diversity patterns in patients with OAPS is thus of paramount clinical importance. This investigation procured peripheral blood specimens from 31 individuals with OAPS, 21 patients diagnosed with systemic lupus erythematosus (SLE), and 22 healthy controls (HC), proceeding with TCR repertoire sequencing. Concurrently, adverse pregnancy outcomes in the OAPS cohort were monitored and documented over an 18-month timeframe. We paid particular attention to disparities in V/J gene utilisation and the prevalence of shared clonotypes amongst OAPS patients and the comparative groups. When juxtaposed with observations from healthy controls and SLE patients, immune repertoire sequencing disclosed irregular T- and B-cell profiles and a contraction of diversity within the OAPS group. Marked variances were found in the genomic rearrangements of the V gene, J gene, and V/J combinations. Utilising a specialised TCRß repertoire, we crafted a predictive model for OAPS classification with robust discriminative capability (AUC = 0.852). Our research unveils alterations in the TCR repertoire among OAPS patients for the first time, positing potential covert autoimmune underpinnings. These findings nominate the TCR repertoire as a prospective peripheral blood biomarker for the clinical diagnosis of OAPS and may offer valuable insights for advancing the understanding of OAPS immunologic mechanisms and prognostic outcomes.
Assuntos
Síndrome Antifosfolipídica , Biomarcadores , Receptores de Antígenos de Linfócitos T , Humanos , Síndrome Antifosfolipídica/imunologia , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/genética , Síndrome Antifosfolipídica/sangue , Feminino , Gravidez , Adulto , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/sangue , Complicações na Gravidez/imunologia , Complicações na Gravidez/genética , Complicações na Gravidez/diagnósticoRESUMO
ABSTRACT: Current guidelines recommend that direct anticoagulants should not be used in prevention of recurrent thrombosis in patients with antiphospholipid syndrome (APS). However, except for triple-positive APS and rivaroxaban use, little evidence supports such recommendation. In a real-life cohort study, we evaluated the risk of thromboembolism and bleeding in patients with APS on apixaban versus vitamin K antagonists (VKA). We enrolled 152 patients with APS (aged 44 years [interquartile range 36-56], 83% women), including 66 patients treated with apixaban 5 mg bid and 86 with warfarin (target international normalized ratio [INR] 2-3). During a median follow-up of 53 months, we recorded venous thromboembolism, ischemic stroke, or myocardial infarction, along with major bleeding. We observed 4 thrombotic events (6.1%, 3 venous thromboembolism and 1 ischemic stroke) in patients on apixaban and 12 events (14%, 9 venous thromboembolism, 2 ischemic strokes and 1 myocardial infarction) in VKA patients. Patients with APS on apixaban had similar risk of recurrent thromboembolism compared with those on warfarin (hazard ratio [HR] = 0.327, 95% confidence interval [CI]: 0.104-1.035). Thromboembolic events occurred less commonly in statin users (8% vs. 50%, P = 0.01) and more frequently in triple-positive APS (50% vs. 22.1%, P = 0.028) and in patients with higher D-dimer at baseline ( P = 0.023); the latter difference was present in the apixaban group ( P = 0.02). Patients on apixaban had similar risk of major bleeding compared with warfarin (HR = 0.54, 95% CI: 0.201-1.448). In real-life patients with APS, apixaban appears to be similar to VKA for the prevention of thromboembolism and risk of bleeding, which might suggest that some patients with APS could be treated with apixaban.
Assuntos
Anticoagulantes , Síndrome Antifosfolipídica , Inibidores do Fator Xa , Hemorragia , Pirazóis , Piridonas , Vitamina K , Varfarina , Humanos , Feminino , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Piridonas/efeitos adversos , Piridonas/uso terapêutico , Piridonas/administração & dosagem , Masculino , Síndrome Antifosfolipídica/tratamento farmacológico , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/sangue , Pessoa de Meia-Idade , Inibidores do Fator Xa/efeitos adversos , Inibidores do Fator Xa/administração & dosagem , Inibidores do Fator Xa/uso terapêutico , Hemorragia/induzido quimicamente , Vitamina K/antagonistas & inibidores , Adulto , Resultado do Tratamento , Fatores de Risco , Anticoagulantes/efeitos adversos , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Varfarina/efeitos adversos , Varfarina/uso terapêutico , Varfarina/administração & dosagem , Fatores de Tempo , Medição de Risco , Recidiva , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/epidemiologia , Infarto do Miocárdio/prevenção & controle , Infarto do Miocárdio/epidemiologia , AVC Isquêmico/prevenção & controle , AVC Isquêmico/diagnóstico , AVC Isquêmico/epidemiologiaRESUMO
BACKGROUND: Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is a rare disease caused by acquired factor II (FII) deficiency and lupus anticoagulant. Patients with LAHPS typically present with thrombosis and bleeding. However, little information is available on the evaluation of coagulation potential in patients with LAHPS. We examined global coagulation potentials in patients with LAHPS during the clinical course in this study. METHODS: Coagulation potentials in two pediatric patients with LAHPS were assessed by measuring clotting time (CT) and clot formation time using Ca2+-triggered rotational thromboelastometry (ROTEM), CT and maximum coagulation velocity using clot waveform analysis (CWA), and lag time and peak thrombin using the thrombin generation assay (TGA). The day of admission was defined as day 0. RESULTS: In case 1, the bleeding symptoms disappeared by day 5. However, the TGA and CWA results were markedly lower than normal, although FII activity (FII:C) returned to within the normal range by day 14. In contrast, ROTEM revealed a recovery to near-normal levels (day 14). All coagulation parameters (day 80) were within normal ranges. In case 2, coagulation potential was severely depressed until day 12, although FII:C returned to normal levels. Bleeding symptoms disappeared on day 19, and the ROTEM data revealed that the parameters were close to the normal range. The coagulation parameters in all assays were normalized on day 75. CONCLUSIONS: Recovery of coagulation potential in patients with LAHPS was slower than the recovery of FII:C. Moreover, ROTEM appeared to be clinically useful for assessing coagulation potential in patients with LAHPS.
Assuntos
Hipoprotrombinemias , Inibidor de Coagulação do Lúpus , Tromboelastografia , Humanos , Hipoprotrombinemias/sangue , Hipoprotrombinemias/diagnóstico , Inibidor de Coagulação do Lúpus/sangue , Feminino , Tromboelastografia/métodos , Masculino , Criança , Testes de Coagulação Sanguínea/métodos , Coagulação Sanguínea/fisiologia , Pré-Escolar , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnósticoRESUMO
OBJECTIVE: To analyze antiphospholipid antibody (aPL)-positive patients using the 2023 American College of Rheumatology/The European Alliance of Associations for Rheumatology (ACR/EULAR) antiphospholipid syndrome (APS) classification criteria and compare the revised Sapporo criteria and the 2023 ACR/EULAR criteria and evaluate whether the 2023 ACR/EULAR criteria provide added value over the revised Sapporo criteria. METHODS: In this descriptive study, 94 aPL-positive patients (with or without APS diagnosis) were identified from two hospital-based registries (Gazi and Hacettepe University). Patients were classified into four groups to compare both criteria sets. These four groups are as follows: (1) patients classified with only the revised Sapporo criteria; (2) patients classified with only the 2023 ACR/EULAR APS criteria; (3) patients classified with both two criteria sets; and (4) patients classified with neither two criteria set. RESULTS: Of the 94 patients, 11 were classified with only the revised Sapporo criteria; one with only the 2023 ACR/EULAR APS criteria; 52 with both criteria sets; and 30 with neither set of criteria. For these 94 patients, the operating characteristics of the 2023 ACR/EULAR APS criteria, using the revised Sapporo criteria as the gold standard, the 2023 ACR/EULAR APS entry criteria demonstrated 100% sensitivity, and the 2023 ACR/EULAR APS classification criteria demonstrated 98% specificity and 82.5% sensitivity. CONCLUSION: The study emphasizes the importance of recognizing differences in clinical manifestations, such as early pregnancy loss without severe preeclampsia (PEC) and/or severe placental insufficiency (PI) and calls for a nuanced discussion on anticardiolipin (aCL) and anti-beta 2-glycoprotein-I (anti-ß2GPI) immunoglobulin G (IgG) cutoff values.
Assuntos
Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica , Valor Preditivo dos Testes , Sistema de Registros , Humanos , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/imunologia , Síndrome Antifosfolipídica/sangue , Feminino , Masculino , Adulto , Gravidez , Pessoa de Meia-Idade , Anticorpos Antifosfolipídeos/sangue , Biomarcadores/sangue , Reprodutibilidade dos Testes , Turquia , Adulto Jovem , Reumatologia/normasRESUMO
OBJECTIVES: To evaluate the effectiveness of the 2023 ACR/EULAR criteria for antiphospholipid syndrome (APS) in a Chinese cohort, and compare them with the Sapporo and revised Sapporo criteria. METHODS: A cohort comprising 436 patients diagnosed with APS and 514 control subjects was enrolled, including 83 with seronegative APS and 86 classified as antiphospholipid antibody (aPL) carriers. We assessed IgG and IgM anticardiolipin antibodies (aCL) and anti-ß2-glycoprotein I (aß2GPI) antibodies using ELISA, along with a systematic collection of lupus anticoagulant data. Subsequently, we compared the sensitivity and specificity across the three classification criteria. RESULTS: The 2023 ACR/EULAR criteria exhibited improved specificity at 98 %, surpassing the revised Sapporo (90 %) and original Sapporo (91 %) criteria. However, this came with decreased sensitivity at 82 %, in contrast to higher sensitivities in the revised Sapporo (98 %) and Sapporo (91 %) criteria. Examining individual components sheds light on the scoring system's rationale within the new criteria. The inclusion of microvascular thrombosis, cardiac valve disease, and thrombocytopenia improved the identification of nine patients previously classified as "probable APS". Insufficient scoring in 78 previously diagnosed APS individuals was linked to traditional risk factor evaluations for thrombotic events, the emphasis on determining whether obstetric events are linked to severe preeclampsia (PEC) or placental insufficiency (PI), and the lower scores assigned to IgM aCL and/or aß2GPI antibody. Seronegative APS remained a challenge, as non-criteria aPL and other methods were not included. CONCLUSIONS: The new criteria presented notable advancements in specificity. This study provides detailed insights into the strengths and possible challenges of the 2023 ACR/EULAR criteria, enhancing our understanding of their impact on clinical practice.
Assuntos
Anticorpos Anticardiolipina , Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica , beta 2-Glicoproteína I , Humanos , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/imunologia , Síndrome Antifosfolipídica/sangue , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Anticorpos Antifosfolipídeos/sangue , Anticorpos Antifosfolipídeos/imunologia , beta 2-Glicoproteína I/imunologia , Anticorpos Anticardiolipina/sangue , China/epidemiologia , Gravidez , Estudos de Coortes , Inibidor de Coagulação do Lúpus/sangue , Sensibilidade e Especificidade , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Povo Asiático , População do Leste AsiáticoRESUMO
Antiphospholipid syndrome is a rare autoimmune disease characterized by persistent antiphospholipid antibodies. Immunoglobulin G plays a vital role in disease progression, with its structure and function affected by glycosylation. We aimed to investigate the changes in the serum immunoglobulin G glycosylation pattern in antiphospholipid syndrome patients. We applied lectin microarray on samples from 178 antiphospholipid syndrome patients, 135 disease controls (including Takayasu arteritis, rheumatoid arthritis and cardiovascular disease) and 100 healthy controls. Lectin blots were performed for validation of significant differences. Here, we show an increased immunoglobulin G-binding level of soybean agglutinin (p = 0.047, preferring N-acetylgalactosamine) in antiphospholipid syndrome patients compared with healthy and disease controls. Additionally, the immunoglobulin G from antiphospholipid syndrome patients diagnosed with pregnancy events had lower levels of fucosylation (p = 0.001, recognized by Lotus tetragonolobus) and sialylation (p = 0.030, recognized by Sambucus nigra I) than those with simple thrombotic events. These results suggest the unique serum immunoglobulin G glycosylation profile of antiphospholipid syndrome patients, which may inform future studies to design biomarkers for more accurate diagnosis of antiphospholipid syndrome and even for the prediction of clinical symptoms in patients.
Assuntos
Síndrome Antifosfolipídica , Imunoglobulina G , Humanos , Síndrome Antifosfolipídica/imunologia , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/diagnóstico , Glicosilação , Feminino , Masculino , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Adulto , Pessoa de Meia-Idade , Gravidez , Lectinas/sangue , Lectinas/metabolismo , Lectinas/imunologia , Biomarcadores/sangue , Análise Serial de Proteínas/métodos , Anticorpos Antifosfolipídeos/sangue , Anticorpos Antifosfolipídeos/imunologia , Lectinas de Plantas/metabolismo , Lectinas de Plantas/imunologia , Idoso , GlicoproteínasRESUMO
BACKGROUND: Improving harmonization of the clinical interpretation of anticardiolipin (aCL) and anti-ß2-glycoprotein I (aß2GPI) antibodies immunoglobulin G (IgG)/immunoglobulin M (IgM) in the diagnosis of antiphospholipid syndrome (APS) is desirable. Likelihood ratios (LRs) with corresponding test-result intervals can identify the power of a test to discriminate between a diseased and nondiseased patient and may be useful for the semiquantitative interpretation of aCL/aß2GPI results. OBJECTIVES: To determine moderate and high thresholds for aCL and aß2GPI IgG/IgM measured with chemiluminescent immunoassay, enzyme-linked immunosorbent assay, fluorescence enzyme immunoassay, and multiplex flow immunoassay. METHODS: aCL and aß2GPI antibodies IgG/IgM were determined with 4 solid-phase systems in a case-control study population including 381 APS patients and 727 controls. Interval-specific LRs (IS-LR) were calculated for ranges determined by prespecified specificity and sensitivity levels. Three methods were used for determining thresholds that separated low, moderate, and high positive antibody levels. Interassay agreement was checked with Cohen's kappa statistics. RESULTS: Assay- and antibody-specific thresholds demonstrated increasing IS-LR, reflecting different clinical significance for low, moderate, and high levels, especially for IgG aCL and aß2GPI and in thrombotic APS. IS-LRs per antibody and unit range were comparable across solid-phase platforms resulting in enhanced harmonization of result interpretation. Agreement between assays for identifying high levels was improved by semiquantitative interpretation compared with that by quantitative reporting. CONCLUSION: aCL and aß2GPI IgG/IgM moderate and high thresholds were determined for 4 analytical platforms. Thresholds improve harmonized interpretation of aCL/aß2GPI levels across platforms. The proposed thresholds should be verified in an independent case-control study to check interlaboratory transferability.
Assuntos
Anticorpos Anticardiolipina , Síndrome Antifosfolipídica , Imunoglobulina G , Inibidor de Coagulação do Lúpus , beta 2-Glicoproteína I , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/imunologia , Humanos , Anticorpos Anticardiolipina/sangue , beta 2-Glicoproteína I/imunologia , Inibidor de Coagulação do Lúpus/sangue , Estudos de Casos e Controles , Imunoglobulina G/sangue , Feminino , Masculino , Anticorpos Antifosfolipídeos/sangue , Funções Verossimilhança , Imunoglobulina M/sangue , Valor Preditivo dos Testes , Ensaio de Imunoadsorção Enzimática/normas , Ensaio de Imunoadsorção Enzimática/métodos , Pessoa de Meia-Idade , Adulto , Reprodutibilidade dos Testes , Biomarcadores/sangue , Medições LuminescentesRESUMO
Antiphospholipid syndrome (APS) is characterized by thrombosis (which may be venous, arterial, or microvascular) and/or pregnancy morbidity in association with persistently positive antiphospholipid antibodies. Although thrombosis and pregnancy morbidity are the main clinical criteria for a diagnosis of APS in the revised Sapporo (Sydney) criteria, recently published American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for APS have significantly refined the diagnostic algorithm to include a scoring system clustered into 6 clinical domains (macrovascular venous thromboembolism, macrovascular arterial thrombosis, microvascular thrombosis, obstetric, cardiac valve, and hematologic). Diagnosis of APS is complicated by the fact that significant heterogeneity exists in patients' clinical presentation, underlying vascular risk factors, and methods of detecting antiphospholipid antibodies. Despite the autoimmune nature of APS, anticoagulation remains the main strategy for secondary prevention of thrombosis. Furthermore, optimal antithrombotic treatment in APS patients with arterial thrombosis remains controversial due to a paucity of data from randomized controlled studies. In this paper, we present 2 cases and highlight the diagnostic and therapeutic challenges they pose and how we approach them in the light of current evidence.
Assuntos
Anticorpos Antifosfolipídeos , Anticoagulantes , Síndrome Antifosfolipídica , Feminino , Humanos , Masculino , Gravidez , Anticorpos Antifosfolipídeos/sangue , Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/diagnóstico , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/terapia , Valor Preditivo dos Testes , Fatores de Risco , Trombose/diagnóstico , Trombose/etiologia , Trombose/terapia , Trombose/sangue , Trombose/prevenção & controle , Resultado do TratamentoRESUMO
BACKGROUND: Antiphospholipid antibody syndrome (APS) is an acquired autoimmune disorder characterized by recurrent venous or arterial thrombosis and/or pregnancy complications. Recently, thrombotic APS was linked to increased neutrophil extracellular traps (NET) formation, suggesting an association between NETs and the severity of APS-related thrombosis. METHODS: We performed a retrospective study on patients tested for presence of antiphospholipid antibodies (990 negative and 374 positive) to evaluate the association between the neutrophil activation state, estimated by the neutrophil reactive index (NEU-RI), a parameter routinely available from some haematology analysers, and antiphospholipid antibodies. RESULTS: We do not observe a difference in NEU-RI values between positive and negative patients globally. However, interestingly, we highlight an association between high titers of IgM and low NEU-RI values indicating a lower neutrophil activation. CONCLUSION: Our data are in line with the recent questioning about the putative clinical consistency of positive solid-phase aPL IgM.
Assuntos
Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica , Biomarcadores , Armadilhas Extracelulares , Imunoglobulina M , Neutrófilos , Humanos , Anticorpos Antifosfolipídeos/sangue , Anticorpos Antifosfolipídeos/imunologia , Estudos Retrospectivos , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Síndrome Antifosfolipídica/sangue , Síndrome Antifosfolipídica/imunologia , Armadilhas Extracelulares/imunologia , Feminino , Masculino , Biomarcadores/sangue , Neutrófilos/imunologia , Pessoa de Meia-Idade , Adulto , Ativação de NeutrófiloRESUMO
Thrombotic antiphospholipid syndrome (TAPS) is characterized by thrombosis and persistently positive tests for antiphospholipid antibodies or lupus anticoagulant (LAC). Triple-positive APS has the highest risk of recurrent thrombosis, but no studies have focused on recurrent thrombosis in patients with single-positive TAPS. We conducted a retrospective cohort study of patients with single-positive TAPS diagnosed at Lifespan Health System, Rhode Island, to determine the rates and risk factors for recurrent thrombosis. Between January 2001 and April 2022, 128 patients were assessed who had single-positive APS (LAC = 98, aCL = 21, aß2GPI = 9) and who had been followed for a total of 1453.8 patient-years (median follow-up 3.04 years). The initial antithrombotic regimen was warfarin in 44 %, a direct oral anticoagulant (DOAC) in 34 %, enoxaparin in 2 %, and no antithrombotic therapy or antiplatelet therapy only in 20 %. Recurrent thrombosis occurred in 16 (12.5 %) with a recurrent thrombosis rate of 3.08 per 100 patient-years. Systemic lupus erythematosus was the only variable significantly associated with recurrent thrombosis in a model adjusted for age, sex, body mass index, and type of positive APS test. All 16 patients with recurrent thrombosis were initially treated with warfarin, and, at the time of recurrent thrombosis, 13 patients remained on warfarin and three were off anticoagulation. In conclusion, the recurrent thrombosis rate in single-positive APS is low, and not all patients with a single-positive test may need indefinite anticoagulation with warfarin. Larger prospective studies are required to confirm this finding and establish optimal anticoagulation regimens for low-risk TAPS.