RESUMEN

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by vascular thrombosis and obstetric morbidity, with accurate laboratory examination of antiphospholipid antibodies (aPLs) being crucial for diagnosis. This study focused on anti-ß2 glycoprotein I (aß2GPI) antibodies and aimed to establish the first population-based cutoff values for aß2GPI IgA/IgM/IgG antibodies in non-pregnant women of reproductive age in Southwest China. The study cohort comprised 181 healthy women of reproductive age for study. Blood samples were collected on an early morning fast. Anti-ß2GPI antibodies including IgA, IgM and IgG were measured in serum using the HOB® BioCLIA kit. According to the Clinical and Laboratory Standards Institute (CLSI) guidelines, the study used non-parametric percentile methods to calculate the 95th, 97.5th, and 99th percentiles cutoff values for aß2GPI IgA/IgM/IgG antibodies, along with corresponding 90% confidence intervals (CI), while excluding outliers. A total of 168 independent samples were collected for verification, including 85 samples from healthy subjects and 83 samples from APS patients, in order to evaluate the analytical performance of the obtained cutoff values. The 99th percentile cutoff values were 3.36 RU/mL for aß2GPI IgA, 27.54 RU/mL for aß2GPI IgM and 1.81 RU/mL for aß2GPI IgG, which indicated that the levels of aß2GPI IgM antibodies were generally higher compared to those of IgA and IgG antibodies. Our established reference range was confirmed to be successful in validating the detected values of aß2GPI antibodies in all healthy controls. With the 99th percentile cutoff value, the sensitivity was 14.46% for aß2GPI IgA, 22.89% for aß2GPI IgG, and 9.64% for aß2GPI IgM in APS patients. This study established population-based cutoff values that are applicable to the local population for the accurate laboratory examination of aß2GPI antibodies in non-pregnant women of reproductive age. The study also recommends paying more attention to IgM positivity in women of reproductive age.

Asunto(s)

Síndrome Antifosfolípido , Inmunoglobulina G , Inmunoglobulina M , beta 2 Glicoproteína I , Humanos , Femenino , beta 2 Glicoproteína I/inmunología , Adulto , China , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/diagnóstico , Inmunoglobulina M/sangre , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunoglobulina A/sangre , Persona de Mediana Edad , Anticuerpos Antifosfolípidos/sangre , Anticuerpos Antifosfolípidos/inmunología , Adulto Joven , Valores de Referencia , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Adolescente

RESUMEN

INTRODUCTION: The objective of this study was to investigate both antiphospholipid antibodies (aPLs) and non-criteria aPLs (NC-aPLs) in relation with pregnancy outcomes. METHODS: We retrospectively analyzed 1574 pregnant women with experienced at least one miscarriage who were tested for aPLs and NC-aPLs, and compared their clinical characteristics, immune biomarkers, and pregnancy outcomes. The χ2 test or Fisher's exact test compared pregnancy outcomes among patients negative for all aPLs, positive for NC­aPLs subtypes, and positive for criteria aPLs subtypes. RESULTS: Multivariate logistic regression analysis indicated that positive aPLs (OR = 2.216, 95 % CI 1.381-3.558), and positive NC-aPLs (OR = 1.619, 95 % CI 1.245-2.106) are linked to adverse outcomes. For fetal loss, positive aPLs (OR = 2.354, 95 % CI 1.448-3.829), NC-aPLs (OR = 1.443, 95 % CI 1.076-1.936) were significant. Premature delivery was associated with positive NC-aPLs (OR = 2.102, 95 % CI 1.452-3.043). In the NC-aPLs positive group, the rate of adverse outcomes was higher in the multiple-positive subgroup (77.8 %) compared to the double-positive (52.3 %) and single-positive (37.0 %) subgroups. The rates of fetal loss and premature delivery were also higher in the multiple-positive NC-aPLs subgroup compared to the single-positive subgroup (48.1 % vs. 22.6 % for fetal loss and 57.1 % vs. 16.5 % for premature delivery). DISCUSSION: Our findings suggest that both aPLs and NC-aPLs are associated with an increased incidence of adverse pregnancy outcomes, and patients presenting with multiple NC-aPLs positivity were found to have a higher incidence of adverse outcomes compared to their single-positive counterparts.

Asunto(s)

Aborto Espontáneo , Anticuerpos Antifosfolípidos , Resultado del Embarazo , Humanos , Embarazo , Femenino , Estudios Retrospectivos , Anticuerpos Antifosfolípidos/sangre , Anticuerpos Antifosfolípidos/inmunología , Adulto , Aborto Espontáneo/inmunología , Aborto Espontáneo/epidemiología , Aborto Espontáneo/sangre , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/diagnóstico , Biomarcadores/sangre , Nacimiento Prematuro/inmunología , Nacimiento Prematuro/epidemiología

RESUMEN

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.

Asunto(s)

Anticuerpos Antifosfolípidos , Síndrome Antifosfolípido , Humanos , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/sangre , Anticuerpos Antifosfolípidos/sangre , Embarazo , Femenino , Inhibidor de Coagulación del Lupus/sangre , Biomarcadores/sangre

RESUMEN

OBJECTIVES: This review aims to identify biological markers associated with the risk of recurrence of thrombotic and/or obstetric events in patients with antiphospholipid syndrome (APS). METHODS: A comprehensive review of literature was conducted to evaluate established and potential novel biological markers associated with thrombosis in APS. To this end, a PubMed literature search was conducted for the last twenty years using the following keywords or their combinations: thrombotic risk, recurrence of thrombosis, risk stratification, severity, predictive value. RESULTS: Previous studies showed that multiple aPL positivity correlates with an increased risk of thrombosis in APS. Moreover, the analysis of N-glycosylation of antiphospholipid antibodies (aPL) revealed that low levels of IgG sialylation, fucosylation or galactosylation increases the pro-inflammatory activity of aPL, predisposing to thrombosis. In addition, quantification of neutrophil extracellular traps (NETs) and antibodies directed against NETs (anti-NETs) in serum demonstrates promising prognostic utility in assessing APS severity. Oxidative stress plays a role in the pathogenicity of APS and paraoxonase 1 (PON1) activity emerges as a promising biomarker of thrombotic risk in APS. Furthermore, identification of novel antigenic targets involved in the pathophysiology of APS, such as lysobisphosphatidic acid (LBPA), had led to the discovery of unconventional aPL, antibodies directed against the LBPA (aLBPA), whose clinical value could make it possible to identify APS patients at high risk of thrombotic recurrence. CONCLUSION: The immunological profile of aPL, N-glycosylation of aPL, quantification of NETs and anti-NETs, analysis of biomarkers of oxidative stress and the discovery of aLBPA offer potential prognostic tools for risk stratification in APS patients.

Asunto(s)

Anticuerpos Antifosfolípidos , Síndrome Antifosfolípido , Biomarcadores , Recurrencia , Trombosis , Humanos , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/sangre , Biomarcadores/sangre , Trombosis/etiología , Trombosis/inmunología , Trombosis/sangre , Anticuerpos Antifosfolípidos/inmunología , Anticuerpos Antifosfolípidos/sangre , Pronóstico , Factores de Riesgo

RESUMEN

INTRODUCTION: Despite thromboprophylaxis, women with antiphospholipid syndrome (APS) face high-risk pregnancies due to proinflammatory and prothrombotic states. This highlights the need for new monitoring and prognostic tools. Recent insights into the pathophysiological role of neutrophil activation and extracellular trap (NET) formation in this syndrome led to the exploration of plasma cell-free DNA (cfDNA), a derivative of NETosis, as a promising biomarker. MATERIALS AND METHODS: cfDNA was isolated and quantified from plasma samples of healthy pregnant women (control group, HC) and women with APS (APS group). We assessed the physiological variability of cfDNA across the three trimesters in HC. Levels of cfDNA were compared between APS and HC by gestational trimester. ROC curve analysis was performed to evaluate the efficacy of cfDNA levels for classifying APS patients. Furthermore, cfDNA levels in pregnant women with APS with obstetric complications were compared to those from uncomplicated pregnancies. RESULTS: Among HC, cfDNA significantly increased in the third trimester compared to the first and second. Elevated cfDNA levels in APS compared to HC were observed in the first and second trimesters. First-trimester cfDNA levels demonstrated the highest classification ability to discriminate between APS and HC patients (AUC: 0.906). Among APS, those with complicated pregnancies (fetal growth restriction, preeclampsia, placenta accreta) exhibited significantly elevated cfDNA levels in the second trimester. CONCLUSIONS: Elevated levels of cfDNA in pregnant women with APS, particularly among those with obstetric complications, supports further investigation into the potential of cfDNA as a valuable tool in the obstetric management of women with APS.

Asunto(s)

Síndrome Antifosfolípido , Ácidos Nucleicos Libres de Células , Embarazo de Alto Riesgo , Humanos , Femenino , Embarazo , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/complicaciones , Ácidos Nucleicos Libres de Células/sangre , Adulto , Embarazo de Alto Riesgo/sangre , Biomarcadores/sangre , Complicaciones del Embarazo/sangre

Asunto(s)

Síndrome Antifosfolípido , Recurrencia , Trombosis , Adolescente , Niño , Preescolar , Femenino , Humanos , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/sangre , Trombosis/etiología

RESUMEN

INTRODUCTION: Antiphospholipid syndrome (APS) is a cause of pregnancy morbidity. We aim to determine the frequency of criteria and non-criteria anti-phospholipid (aPL) autoantibodies in patients admitted for unexplained fetal death (UFD), pre-eclampsia (PE) and/or fetal growth restriction (FGR). METHODS: All consecutive patients with UFD, PE and/or FGR followed in the department of Obstetrics, Bichat Hospital, University of Paris, Paris, between January 2019 and December 2021 were screened. Patients with available serum stored from the index pregnancy were included. Patients with previously known APS or twin pregnancy were excluded. Testing for aPL autoantibodies included anti-cardiolipin (aCL), anti-ß2GPI (aß2GPI), anti-phosphatidylethanolamine (aPE), anti-phosphatidylserine/prothrombin (aPS/PT) IgG/IgM and anti-annexin V IgG. When available, placenta specimens were analyzed by a pathologist blinded to the aPL status. All clinical characteristics, pregnancy features, and comorbidities were extracted from electronic medical records. RESULTS: Overall 167 (32 (28.8-35.7) years) patients with UFD (n = 28; 16.8 %), PE (n = 60; 35.9 %) and/or FGR (n = 105; 62.9 %) were screened for aPL autoantibodies. Moderate titers of aPL autoantibodies were detected in 33 (n = 33/167, 19.8 %) patients. aPL autoantibodies were non-criteria aPE IgG/IgM in most cases (n = 28/33, 84.8 %). aPS/PT IgG/IgM were found in 11 (n = 11/33, 33.3 %) cases and aCL or aß2GP1 IgG/IgM in 4 (n = 4/33, 12.1 %). Multivariable logistic regression showed that aPL autoantibodies were mostly associated with UFD (OR 4.37 [1.72-11.20], p = 0.002), PE ≤ 34th week of gestation (3.22 [0.86-11.90], p = 0.070) and chronic deciduitis (8.03 [0.89-67.2], p = 0.060) DISCUSSION: The frequency of aPL autoantibodies, mostly aPE, is high in patients with late pregnancy morbidity and may qualify obstetrical APS.

Asunto(s)

Anticuerpos Antifosfolípidos , Síndrome Antifosfolípido , Humanos , Femenino , Embarazo , Adulto , Anticuerpos Antifosfolípidos/sangre , Anticuerpos Antifosfolípidos/inmunología , Estudios Transversales , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/sangre , Retardo del Crecimiento Fetal/inmunología , Retardo del Crecimiento Fetal/sangre , Muerte Fetal , Preeclampsia/inmunología , Preeclampsia/sangre , Complicaciones del Embarazo/inmunología , Complicaciones del Embarazo/sangre

RESUMEN

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.

Asunto(s)

Síndrome Antifosfolípido , Enfermedad Crítica , Trombocitopenia , Microangiopatías Trombóticas , Humanos , Femenino , Persona de Mediana Edad , Masculino , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/sangre , Estudios Retrospectivos , Adulto , Trombocitopenia/complicaciones , Trombocitopenia/sangre , Microangiopatías Trombóticas/sangre , Microangiopatías Trombóticas/etiología , Microangiopatías Trombóticas/complicaciones , Trombosis/etiología , Unidades de Cuidados Intensivos , Francia/epidemiología , Mortalidad Hospitalaria , Anemia/sangre , Anemia/complicaciones , Anemia/etiología , Proteína ADAMTS13/sangre , Recuento de Plaquetas

RESUMEN

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.

Asunto(s)

Anticuerpos Antifosfolípidos , Síndrome Antifosfolípido , Ataque Isquémico Transitorio , Humanos , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/diagnóstico por imagen , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/inmunología , Femenino , Anticuerpos Antifosfolípidos/sangre , Anticuerpos Antifosfolípidos/inmunología , Ataque Isquémico Transitorio/diagnóstico por imagen , Ataque Isquémico Transitorio/diagnóstico , Imagen por Resonancia Magnética , Persona de Mediana Edad , Adulto

Asunto(s)

Síndrome Antifosfolípido , Endotelio Vascular , Humanos , Síndrome Antifosfolípido/sangre , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiopatología , Endotelio Vascular/efectos de los fármacos , Femenino , Microvasos/metabolismo , Microvasos/efectos de los fármacos , Microvasos/patología , Microvasos/fisiopatología , Microvasos/inmunología , Masculino , Adulto , Anticuerpos Antifosfolípidos/sangre , Venas , Persona de Mediana Edad

Asunto(s)

Anticuerpos Antifosfolípidos , Síndrome Antifosfolípido , Reumatología , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/clasificación , Humanos , Anticuerpos Antifosfolípidos/sangre , Reumatología/normas , Reumatología/métodos , Europa (Continente) , Estados Unidos , Sociedades Médicas , Reproducibilidad de los Resultados

Asunto(s)

Anticuerpos Antifosfolípidos , Síndrome Antifosfolípido , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/clasificación , Humanos , Anticuerpos Antifosfolípidos/sangre , Reproducibilidad de los Resultados

RESUMEN

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.

Asunto(s)

Anticuerpos Antifosfolípidos , Síndrome Antifosfolípido , Ensayo de Inmunoadsorción Enzimática , Humanos , Ensayo de Inmunoadsorción Enzimática/métodos , Anticuerpos Antifosfolípidos/sangre , Anticuerpos Antifosfolípidos/inmunología , Anticuerpos Antifosfolípidos/análisis , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/sangre , Femenino , Masculino , Adulto

RESUMEN

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.

Asunto(s)

Hipoprotrombinemias , Inhibidor de Coagulación del Lupus , Tromboelastografía , Humanos , Hipoprotrombinemias/sangre , Hipoprotrombinemias/diagnóstico , Inhibidor de Coagulación del Lupus/sangre , Femenino , Tromboelastografía/métodos , Masculino , Niño , Pruebas de Coagulación Sanguínea/métodos , Coagulación Sanguínea/fisiología , Preescolar , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/diagnóstico

RESUMEN

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.

Asunto(s)

Anticoagulantes , Síndrome Antifosfolípido , Inhibidores del Factor Xa , Hemorragia , Pirazoles , Piridonas , Vitamina K , Warfarina , Humanos , Femenino , Pirazoles/efectos adversos , Pirazoles/uso terapéutico , Piridonas/efectos adversos , Piridonas/uso terapéutico , Piridonas/administración & dosificación , Masculino , Síndrome Antifosfolípido/tratamiento farmacológico , Síndrome Antifosfolípido/complicaciones , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/sangre , Persona de Mediana Edad , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/administración & dosificación , Inhibidores del Factor Xa/uso terapéutico , Hemorragia/inducido químicamente , Vitamina K/antagonistas & inhibidores , Adulto , Resultado del Tratamiento , Factores de Riesgo , Anticoagulantes/efectos adversos , Anticoagulantes/uso terapéutico , Anticoagulantes/administración & dosificación , Warfarina/efectos adversos , Warfarina/uso terapéutico , Warfarina/administración & dosificación , Factores de Tiempo , Medición de Riesgo , Recurrencia , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/epidemiología , Infarto del Miocardio/prevención & control , Infarto del Miocardio/epidemiología , Accidente Cerebrovascular Isquémico/prevención & control , Accidente Cerebrovascular Isquémico/diagnóstico , Accidente Cerebrovascular Isquémico/epidemiología

RESUMEN

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.

Asunto(s)

Síndrome Antifosfolípido , Biomarcadores , Receptores de Antígenos de Linfocitos T , Humanos , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/genética , Síndrome Antifosfolípido/sangre , Femenino , Embarazo , Adulto , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/inmunología , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/sangre , Complicaciones del Embarazo/inmunología , Complicaciones del Embarazo/genética , Complicaciones del Embarazo/diagnóstico

RESUMEN

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.

Asunto(s)

Anticuerpos Antifosfolípidos , Síndrome Antifosfolípido , Humanos , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/inmunología , Anticuerpos Antifosfolípidos/sangre , Femenino , Embarazo , Anticuerpos Anticardiolipina/sangre , Inhibidor de Coagulación del Lupus/sangre , Ensayo de Inmunoadsorción Enzimática

RESUMEN

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.

Asunto(s)

Anticuerpos Antifosfolípidos , Síndrome Antifosfolípido , COVID-19 , SARS-CoV-2 , Humanos , COVID-19/inmunología , Masculino , Femenino , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/sangre , Adulto , Persona de Mediana Edad , Anticuerpos Antifosfolípidos/sangre , SARS-CoV-2/inmunología , China/epidemiología , Anticuerpos Anticardiolipina/sangre , beta 2 Glicoproteína I/inmunología , Inmunoglobulina G/sangre , Anciano

RESUMEN

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.

Asunto(s)

Anticuerpos Anticardiolipina , Síndrome Antifosfolípido , Inmunoglobulina G , Inhibidor de Coagulación del Lupus , beta 2 Glicoproteína I , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/sangre , Síndrome Antifosfolípido/inmunología , Humanos , Anticuerpos Anticardiolipina/sangre , beta 2 Glicoproteína I/inmunología , Inhibidor de Coagulación del Lupus/sangre , Estudios de Casos y Controles , Inmunoglobulina G/sangre , Femenino , Masculino , Anticuerpos Antifosfolípidos/sangre , Funciones de Verosimilitud , Inmunoglobulina M/sangre , Valor Predictivo de las Pruebas , Ensayo de Inmunoadsorción Enzimática/normas , Ensayo de Inmunoadsorción Enzimática/métodos , Persona de Mediana Edad , Adulto , Reproducibilidad de los Resultados , Biomarcadores/sangre , Mediciones Luminiscentes

RESUMEN

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.

Asunto(s)

Anticuerpos Anticardiolipina , Anticuerpos Antifosfolípidos , Síndrome Antifosfolípido , beta 2 Glicoproteína I , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Embarazo , Anticuerpos Anticardiolipina/sangre , Anticuerpos Antifosfolípidos/sangre , Anticuerpos Antifosfolípidos/inmunología , Síndrome Antifosfolípido/diagnóstico , Síndrome Antifosfolípido/inmunología , Síndrome Antifosfolípido/sangre , Pueblo Asiatico , beta 2 Glicoproteína I/inmunología , China/epidemiología , Estudios de Cohortes , Pueblos del Este de Asia , Inmunoglobulina M/sangre , Inmunoglobulina M/inmunología , Inhibidor de Coagulación del Lupus/sangre , Sensibilidad y Especificidad