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RMD Open Mar 2023Antiphospholipid syndrome (APS) is defined by the association of thromboembolic and/or obstetrical clinical manifestations and the presence of antiphospholipid...
OBJECTIVE
Antiphospholipid syndrome (APS) is defined by the association of thromboembolic and/or obstetrical clinical manifestations and the presence of antiphospholipid antibodies. The objective of our study was to evaluate the impact of the triple-positive profile in a cohort of 204 APS patients.
METHODS
We conducted a retrospective study, including patients with primary or secondary APS, meeting the Sydney criteria with at least one thrombotic and/or obstetrical complication. Clinical characteristics and the risk of relapse (defined by the occurrence of a new thrombotic event and/or a new adverse obstetrical event) between triple-positive and non-triple-positive APS patients were compared.
RESULTS
204 patients were included in our study, 68 were triple-positive and 136 were single or double positive. 122 patients (59.8%) had primary APS. 67 patients (32.8%) had obstetrical APS, with a higher rate among triple-positive patients (45.6% vs 26.5%, p=0.010), and 170 patients (83.3%) had thrombotic APS, without difference between triple-positive and others. Thrombotic events were more often venous (56.4%) than arterial (37.7%). Triple-positive patients had more placental complications than others (17.6% vs 2.9%, p=0.001) and more non-criteria events (48.5% vs 25.7%, p=0.002). Among non-criteria events, there was a higher frequency of Sneddon syndrome in triple-positive patients (7.4% vs 0.7%, p=0.028). The relapse rate was higher in triple-positive patients than in others (63.2% vs 39,7%, p=0002). In multivariate analysis, the triple-positive profile was associated with a higher risk of relapse (HR 1.63; 95% CI 1.04 to 2.55; p=0.031).
CONCLUSION
The triple-positivity is associated with a higher risk of relapse and obstetrical complications.
Topics: Humans; Female; Pregnancy; Antiphospholipid Syndrome; Retrospective Studies; Placenta; Antibodies, Antiphospholipid; Prognosis; Thrombosis
PubMed: 37001919
DOI: 10.1136/rmdopen-2022-002534 -
RMD Open Aug 2023To examine blood pressure (BP) and lipid treatment eligibility in antiphospholipid syndrome (APS) according to European Alliance of Associations for Rheumatology (EULAR)...
BACKGROUND
To examine blood pressure (BP) and lipid treatment eligibility in antiphospholipid syndrome (APS) according to European Alliance of Associations for Rheumatology (EULAR) and European Society of Cardiology (ESC) recommendations.
METHODS
Systematic Coronary Risk Evaluation (SCORE), modified-SCORE, diabetes mellitus (DM)-equivalent risk classifiers (DIME) and disease-related classifiers -type of thrombotic events (APS), antiphospholipid-antibody profile (aPL) and adjusted Global APS Score for cardiovascular disease- were used to calculate predicted low-moderate, high and very-high cardiovascular risk (CVR) in 111 patients with APS without prior atherosclerotic cardiovascular events or DM. Actual CVR (AR) was determined according to ESC guidelines, including carotid/femoral plaque presence. In low-moderate SCORE-predicted risk patients, classification ability and agreement for BP or lipid treatment was tested with Matthews' correlation coefficient (MCC) and Cohen's kappa, respectively, using the AR classes as reference qualifiers.
RESULTS
SCORE underestimated high/very-high-AR in >50% of cases. SCORE-guided BP/lipid treatment eligibility was 4.2%/12.6% for high, 10.5%/16.8% for very-high AR patients, while 5.3% of low-moderate AR cases were eligible for lipid-lowering therapy. For BP treatment, MCC was higher using DIME for low-moderate and very-high-risk (0.33 and 0.32, respectively), and using modified-SCORE+APS (MCC=0.25) for high-risk patients. Eligibility agreement was better with DIME+APS or aPL (kappa=0.51) for high-risk, and DIME (kappa=0.31) for very-high-risk patients. For lipid treatment, both classification ability and eligibility agreement were stronger with SCORE (or modified-SCORE)+APS in low-moderate (MCC/kappa=0.43/0.41) and very-high risk (MCC/kappa=0.30/0.30), and with DIME+aPL (MCC/kappa=0.50/0.50) in high-risk patients, respectively.
CONCLUSION
Multimodal risk assessment including disease-related and cardiometabolic features used for high-risk diseases such as DM can improve CVR management in APS.
Topics: Humans; Antiphospholipid Syndrome; Risk Factors; Blood Pressure; Rheumatology; Cardiology; Lipids
PubMed: 37558493
DOI: 10.1136/rmdopen-2023-003326 -
Frontiers in Immunology 2023Bleeding complications are recognized as relatively infrequent manifestations of antiphospholipid syndrome (APS), and the safety of antithrombotic therapy during...
BACKGROUND
Bleeding complications are recognized as relatively infrequent manifestations of antiphospholipid syndrome (APS), and the safety of antithrombotic therapy during pregnancy is of concern. This study aims to assess the risk factors and possible associations between bleeding complications and adverse pregnancy outcomes (APOs) in patients with APS.
METHODS
A retrospective cohort study was conducted at the Peking University People's Hospital. The clinical and immunologic features, bleeding complications, treatment, and pregnancy outcomes of patients with APS were collected. Univariate and multivariate logistic regression analyses were applied to assess the associations between APOs and bleeding complications.
RESULTS
A total of 176 participants with obstetric APS were included in the analysis. There were 66 (37.50%) patients with APS with hemorrhage complications and 86 (48.86%) patients with APS with APOs. Mucocutaneous hemorrhage was associated with APOs including fetal death after 12 weeks [odds ratio (OR) = 10.73, 95% confidence interval (CI): 1.61-71.74, p = 0.014], preterm delivery prior to 34 weeks (OR = 8.30, 95% CI: 2.31-29.84, p = 0.001), and small for gestational age (OR = 4.17, 95% CI: 1.22-14.21, p = 0.023) in univariate logistic regression analyses. It also independently associated with preterm delivery prior to 34 weeks (OR = 40.29, 95% CI: 1.45-1121.32, p = 0.030) in multivariate logistic regression analyses. Receiver operating characteristic (ROC) analysis evaluating the accuracy of these factors for preterm delivery prior to 34 weeks showed that the area under ROC curve was 0.871.
CONCLUSION
The study shows that mucocutaneous hemorrhage may be an indication of the occurrence of APOs in obstetric patients with APS.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Antiphospholipid Syndrome; Pregnancy Outcome; Premature Birth; Retrospective Studies; Hemorrhage; Risk Factors
PubMed: 37006292
DOI: 10.3389/fimmu.2023.1145146 -
Frontiers in Immunology 2021Antiphospholipid syndrome (APS) is a systemic autoimmune disease that can lead to thrombosis and/or pregnancy complications. Exosomes, membrane-encapsulated vesicles...
BACKGROUND
Antiphospholipid syndrome (APS) is a systemic autoimmune disease that can lead to thrombosis and/or pregnancy complications. Exosomes, membrane-encapsulated vesicles that are released into the extracellular environment by many types of cells, can carry signals to recipient cells to affect angiogenesis, apoptosis, and inflammation. There is increasing evidence suggesting that exosomes play critical roles in pregnancy. However, the contribution of exosomes to APS is still unknown.
METHODS
Peripheral plasma was collected from healthy early pregnancy patients (NC-exos) and early pregnancy patients with APS (APS-exos) for exosome extraction and characterization. The effect of exosomes from different sources on pregnancy outcomes was determined by establishing a mouse pregnancy model. Following the coincubation of exosomes and human umbilical vein endothelial cells (HUVECs), functional tests examined the features of APS-exos. The APS-exos and NC-exos were analyzed by quantitative proteomics of whole protein tandem mass tag (TMT) markers to explore the different compositions and identify key proteins. After incubation with HUVECs, functional tests investigated the characteristics of key exosomal proteins. Western blot analysis was used to identify the key pathways.
RESULTS
In the mouse model, APS-exos caused an APS-like birth outcome. In vitro experiments showed that APS-exos inhibited the migration and tube formation of HUVECs. Quantitative proteomics analysis identified 27 upregulated proteins and 9 downregulated proteins in APS-exos versus NC-exos. We hypothesized that apolipoprotein H (APOH) may be a core protein, and the analysis of clinical samples was consistent with finding from the proteomic TMT analysis. APOH-exos led to APS-like birth outcomes. APOH-exos directly enter HUVECs and may play a role through the phospho-extracellular signal-regulated kinase pathway.
CONCLUSIONS
Our study suggests that both APS-exos and APOH-exos impair vascular development and lead to pregnancy complications. APOH-exos may be key actors in the pathogenesis of APS. This study provides new insights into the pathogenesis of APS and potential new targets for therapeutic intervention.
Topics: Animals; Antiphospholipid Syndrome; Biological Transport; Biomarkers; Cells, Cultured; Disease Models, Animal; Disease Susceptibility; Exosomes; Female; Gene Expression Profiling; Gene Expression Regulation; Human Umbilical Vein Endothelial Cells; Humans; Mice; Phenotype; Phosphorylation; Pregnancy; Proteome; Proteomics; beta 2-Glycoprotein I
PubMed: 34040601
DOI: 10.3389/fimmu.2021.604222 -
Nature Reviews. Nephrology May 2014Antiphospholipid syndrome (APS) is an autoimmune disease defined by the presence of arterial or venous thrombotic events and/or pregnancy morbidity in patients who test... (Review)
Review
Antiphospholipid syndrome (APS) is an autoimmune disease defined by the presence of arterial or venous thrombotic events and/or pregnancy morbidity in patients who test positive for antiphospholipid antibodies (aPLs). APS can be isolated (known as primary APS) or associated with other autoimmune diseases, such as systemic lupus erythematosus (SLE; known as secondary APS). The kidney is a major target organ in APS and renal thrombosis can occur at any level within the vasculature of the kidney (renal arteries, intrarenal arteries, glomerular capillaries and renal veins); events reflect the site and size of the involved vessels. Histological findings vary widely, including ischaemic glomeruli and thrombotic lesions without glomerular or arterial immune deposits on immunofluorescence. Renal prognosis is affected by the presence of aPLs in patients with lupus nephritis and can be poor. In patients with SLE and aPLs, biopsy should be performed because inflammatory and thrombotic lesions require different therapeutic approaches. Renal involvement in patients with definite APS is treated by anticoagulation with long-term warfarin. The range of renal manifestations associated with APS is broadening and, therefore, aPLs have increasing relevance in end-stage renal disease, transplantation and pregnancy.
Topics: Adult; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Female; Humans; Infarction; Kidney; Kidney Diseases; Kidney Failure, Chronic; Lupus Erythematosus, Systemic; Lupus Nephritis; Middle Aged; Pregnancy; Renal Veins; Thrombosis; Warfarin
PubMed: 24642799
DOI: 10.1038/nrneph.2014.38 -
Journal of Korean Medical Science Jan 2021Antiphospholipid syndrome (APS), which is characterized by the presence of antiphospholipid antibodies (aPL), is associated with increased risk of thrombosis and... (Review)
Review
Antiphospholipid syndrome (APS), which is characterized by the presence of antiphospholipid antibodies (aPL), is associated with increased risk of thrombosis and obstetric complications, including preterm delivery and recurrent pregnancy losses. APS shows diverse clinical manifestations and the risk of complications varies among clinical subtypes. Although these patients are usually treated with aspirin and anticoagulants, the optimal treatment in various clinical settings is unclear, as the risk of complications vary among clinical subtypes and the management strategy depends on whether the patient is pregnant or not. Also, there are unmet needs for the evidence-based, pregnancy-related treatment of asymptomatic women positive for aPL. This review focuses on the management of positive aPL or APS in pregnant and postpartum women, and in women attempting to become pregnant. For asymptomatic aPL positive women, no treatment, low dose aspirin (LDA) or LDA plus anticoagulants can be considered during antepartum and postpartum. In obstetric APS patients, preconceptional LDA is recommended. LDA plus low molecular weight heparin is administered after confirmation of pregnancy. Vascular APS patients should take frequent pregnancy test and receive heparin instead of warfarin after confirmation of pregnancy. During pregnancy, heparin plus LDA is recommended. Warfarin can be restarted 4 to 6 hours after vaginal delivery and 6 to 12 hours after cesarean delivery. Most importantly, a tailored approach and patient-oriented treatment are mandatory.
Topics: Antibodies, Antiphospholipid; Anticoagulants; Antiphospholipid Syndrome; Aspirin; Female; Heparin, Low-Molecular-Weight; Humans; Postpartum Period; Pregnancy; Thrombosis
PubMed: 33496084
DOI: 10.3346/jkms.2021.36.e24 -
Frontiers in Immunology 2022Antiphospholipid syndrome (APS), characterized by artherial and/or venous thrombosis, pregnancy morbidity and "antiphospholipid" antibodies (aPLs), is more common in...
Antiphospholipid syndrome (APS), characterized by artherial and/or venous thrombosis, pregnancy morbidity and "antiphospholipid" antibodies (aPLs), is more common in women than in men, with a female to male ratio of about 3.5:1. Only few studies have investigated the clinical differences between male and female patients with APS. Therefore, this study was aimed to analyze the differences of clinical manifestations and laboratory tests, at diagnosis, between female and male APS patients and the clinical outcome. We enrolled 191 consecutive APS patients (125 with primary APS, PAPS, and 66 with secondary APS, SAPS) with a female predominant ratio of approximately 3:1 (142 vs 49). The prevalence of PAPS was higher in males than females (p<0.001). The analysis of aPL profile revealed that high IgM anti-cardiolipin (aCL) and high-medium IgG aCL titers were more frequent in males. In thrombotic APS peripheral arterial thrombosis was more common in male than female patients (p=0.049), as well as myocardial infarction (p=0.031). Multivariate analysis to correct for cardiovascular risk factors, high titer of aPLs and triple positivity for aPLs, revealed that the odds ratio for myocardial infarction in male was 3.77. Thus, APS may be considered as a disease in which serological (IgM titer) and clinical profiles are influenced by gender.
Topics: Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Cardiolipins; Female; Humans; Immunoglobulin M; Male; Myocardial Infarction; Pregnancy; Sex Factors; Thrombosis
PubMed: 35860235
DOI: 10.3389/fimmu.2022.932181 -
Biomolecules Mar 2023Despite recent advances in treatment and significant improvements in prognosis, thrombosis remains the major cause of death in systemic lupus erythematosus (SLE).... (Review)
Review
Despite recent advances in treatment and significant improvements in prognosis, thrombosis remains the major cause of death in systemic lupus erythematosus (SLE). Antiphospholipid antibodies (aPL) are the main triggers of thrombosis in patients with SLE, with a frequency of approximately 30-40%. Lupus anticoagulant, anticardiolipin, and anti-β2-glycoprotein I antibodies, which are included in the criteria for antiphospholipid syndrome, and 'non-criteria' aPL such as anti-phosphatidylserine/prothrombin complex antibodies, are risk factors for thrombosis in patients with SLE. Multiple positivity for aPL is also associated with an increased risk of thrombosis, and scores calculated from aPL profiles can predict the risk of developing thrombosis. Although there is insufficient evidence for treatment, aPL-positive SLE patients should/may be treated with anticoagulants and/or low-dose aspirin as appropriate. This review summarises the evidence on the clinical significance of the aPL profile as a biomarker of thrombophilia in patients with SLE.
Topics: Humans; Antibodies, Antiphospholipid; Lupus Erythematosus, Systemic; Antiphospholipid Syndrome; Thrombophilia; Thrombosis; Biomarkers
PubMed: 37189365
DOI: 10.3390/biom13040617 -
Journal of Thrombosis and Thrombolysis Oct 2021Antiphospholipid antibodies induce a pro-inflammatory and hypercoagulable state that lead to increased risk of thrombosis. Whether oxidative damage contributes...
Antiphospholipid antibodies induce a pro-inflammatory and hypercoagulable state that lead to increased risk of thrombosis. Whether oxidative damage contributes thrombosis risk is a matter of debate. We evaluated the association between oxidative stress and thrombosis in primary antiphospholipid syndrome (t-PAPS). Plasma total antioxidant capacity and the levels of malondialdehyde (TBARs), carbonyl protein, and 8-isoprostane in plasma were determined in a group of patients with t-PAPS and in individuals without a history of thrombosis (controls) using commercial ELISA assays. The levels of these plasma markers of oxidative stress were compared between t-PAPS and controls using Mann-Whitney test. A total of 70 patients with t-PAPS and 74 controls were included. Overall, measurements of all plasma oxidative stress markers were similar between t-PAPS patients and controls. In a subgroup analysis, patients with t-PAPS and arterial thrombosis had a higher antioxidant capacity as compared to controls. Thrombotic PAPS was not associated with increased levels of oxidative stress markers, in comparison with individuals without thrombosis. Even though it is not possible to rule out that a mild oxidative damage, not detected by plasma markers, occurs in t-PAPS, our results suggest that measuring plasma oxidative stress markers has limited clinical relevance in t-PAPS.
Topics: Antibodies, Antiphospholipid; Antioxidants; Antiphospholipid Syndrome; Biomarkers; Humans; Oxidative Stress; Thrombosis
PubMed: 34224066
DOI: 10.1007/s11239-021-02509-0 -
European Review For Medical and... Jan 2022The aim of the study was to report about a patient with discoid lupus erythematosus (DLE) who developed antiphospholipid syndrome (APS) 12 years after DLE diagnosis and... (Review)
Review
OBJECTIVE
The aim of the study was to report about a patient with discoid lupus erythematosus (DLE) who developed antiphospholipid syndrome (APS) 12 years after DLE diagnosis and review related literature.
PATIENTS AND METHODS
This is a case report of a 34-year-old woman with DLE who developed APS. A review of articles published in the PubMed/MEDLINE, LILACS, and SciELO databases from 1966 to October 2020 was conducted using the following search terms: "antiphospholipid syndrome," "antiphospholipid antibodies," and "discoid lupus erythematosus" No language limitation was applied.
RESULTS
Besides the present case, 5 case reports were identified. One case-control and two cross-sectional studies on antiphospholipid antibodies with or without APS in DLE were also reviewed. These studies revealed that APS can develop even 37 years after DLE was diagnosed. The case-control study found that patients with DLE have more anticardiolipin antibodies than controls. In contrast, one cross-sectional study showed a low prevalence of antiphospholipid antibodies in their group of patients, which was similar to findings in the general population.
CONCLUSIONS
This study reviewed previous articles on DLE cases associated with antiphospholipid antibodies and/or APS, adding a new case description.
Topics: Adult; Antibodies, Antiphospholipid; Antiphospholipid Syndrome; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Lupus Erythematosus, Discoid; Lupus Erythematosus, Systemic
PubMed: 35049016
DOI: 10.26355/eurrev_202201_27744