Search Results (35)

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by venous and arterial thrombosis and obstetric complications, driven by antiphospholipid antibodies (APLAs). This review synthesizes the latest advancements and current understanding, diagnosis, and treatment of APS. APLAs, including lupus anticoagulant (LAC), anticardiolipin (aCL), and anti-β2-glycoprotein I (aβ2-GPI), interfere with coagulation and endothelial function, as well as with placental health. APS can be primary or secondary; it is often associated with systemic autoimmune diseases like lupus. The pathogenesis of APS remains only partially understood. APLAs promote thrombosis through endothelial damage, platelet activation, and inflammatory signaling pathways. Laboratory diagnosis relies on persistent positivity for APLAs and LAC through tests like ELISA and clotting assays, following a three-step confirmation process. New integrated test systems have been introduced to improve standardization. Classification criteria have evolved, with the 2023 EULAR-ACR criteria providing a weighted, domain-based scoring system, enhancing diagnostic precision. Catastrophic APS (CAPS) is a severe, rare manifestation of APS, characterized by multi-organ failure due to rapid, widespread microthrombosis and systemic inflammation, which requires urgent anticoagulation. Seronegative APS is proposed for patients with clinical features of APS but negative standard antibody tests, possibly due to non-criteria antibodies or transient immunosuppression. Treatment primarily involves long-term anticoagulation with vitamin K antagonists; direct oral anticoagulants are generally not recommended. APS diagnosis and management remain complex due to clinical heterogeneity and laboratory challenges. Continued refinement of diagnostic tools and criteria is essential for improving outcomes in this life-threatening condition. Full article

Objectives: We aimed to quantify the damage burden measured using the Damage Index for Antiphospholipid Syndrome (DIAPS) in patients with antiphospholipid syndrome (APS) and identify patients with high damage as well as any correlations of damage with subclinical atherosclerosis. Methods: Patient damage was assessed via DIAPS. Based on demographic, clinical and laboratory characteristics, patients were divided into two subgroups: thrombotic APS patients with high vs. low damage, and non-thrombotic aPL-positive patients with vs. without damage. Participants underwent carotid/femoral ultrasound for atherosclerotic plaque detection and carotid–femoral and carotid-radial pulse wave velocity (PWV). Results: We included 112 patients with an APS diagnosis, 57 (50.9%) with primary APS and 55 (49.1%) with associated SLE. Cardiovascular (CVD) risk factors and complications were significantly more frequent in the thrombotic group, as well as in patients with high damage within the thrombotic group. We did not identify any risk factors for increased damage in the non-thrombotic group. Atherosclerotic plaque presence was present in 27 (24%) of the patients in this study with the same frequency in the APS and APS/SLE groups (p = 0.5446). Pulse wave velocity (PWV) was elevated in 27–32% patients according to analyzed arteries. Elevated PWV was more frequent in the APS group in comparison to APS/SLE only between carotid and radial arteries (p = 0.0012). Both atherosclerotic plaque presence and PWV did not correlate with damage severity. Conclusions: DIAPS indicates substantial damage in APS patients in our study. High organ damage mainly affected thrombotic patients and was related to CVD complications. At the same time, screening of subclinical atherosclerosis seems not to predict higher damage in APS patients. Full article

Pulmonary arterial hypertension (PAH) is a severe complication associated with connective tissue diseases (CTDs), which is characterized by a significant influence on the patient’s prognosis and mortality. The prevalence of PAH varies depending on the type of CTD. Still, it is highly prevalent in patients with systemic sclerosis (SSc), systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), and primary Sjögren’s syndrome (pSS). Identifying rheumatic disease-specific risk factors is crucial for early diagnosis and intervention. Risk factors for PAH development include specific sociological factors (related to race, gender, and age), clinical features (particularly severe Raynaud’s phenomenon and multiple telangiectasias), cardiological factors (pericarditis and left heart disease), biochemical factors (elevated NT-proBNP and decreased HDL-cholesterol), serological factors (presence of ANA, e.g., anti-U1-RNP or SSA, and antiphospholipid antibodies), and pulmonary factors (interstitial lung disease and decreased DLCO or DLCO/alveolar volume ratio < 70%, FVC/DLCO > 1.6). The analysis of risk factors can be the most useful during the selection of patients at high risk of PAH development. The initial diagnosis of PAH is usually based on transthoracic echocardiography (TTE) and is finally confirmed by right heart catheterization (RHC). Targeted therapies can improve outcomes and include endothelin receptor antagonists, prostacyclin analogs, phosphodiesterase inhibitors, and tailored immunosuppressive treatments. Effective management strategies require a multidisciplinary approach involving rheumatologists, cardiologists, and pulmonologists. The risk stratification and individualized treatment strategies can enhance survival and quality of life in patients with PAH-CTD. Full article

Antiphospholipid antibody (aPL)-induced activation of the mTOR (mammalian target of rapamycin) signaling pathway in endothelial cells plays a role in the pathogenesis of vascular lesions in antiphospholipid syndrome (APS). However, there are no data on whether this mechanism also contributes to the development of skin ulcers commonly observed in APS. We investigated the activation of mTOR in skin specimens from aPL-positive and aPL-negative patients with leg ulcers. Patients with leg ulcers who had primary or secondary APS or no detectable aPLs were included in the study. Biopsies were taken from the ulcer edges and the adjacent non-ulcerated skin areas. Activation of mTORC1 (mTOR Complex1) and mTORC2 (mTOR Complex2) in endothelial cells was determined by immunohistochemical analysis of phosphorylated ribosomal S6 protein (pS6RP) and phosphorylated protein kinase B (pAKT), respectively. In all aPL-positive patients, regardless of whether they had primary or secondary APS, we found a positive immunohistochemical reaction to pS6RP (mTORC1 activation) in the endothelial cells of the ulcer samples. On the other hand, pS6RP could not be detected in samples from aPL-negative chronic venous ulcers. Furthermore, pS6RP was not present in samples taken from the unaffected skin adjacent to the ulcers in aPL-positive patients. The pAKT reaction (mTORC2) was negative in both aPL-positive and aPL-negative patients, both in the ulcers and in the periulcer skin. Activation of the mTOR pathway may contribute to ulcer development in APS. The mTORC1 may be a target for therapeutic modification in APS-associated skin ulcers. Full article

Background: Antiphospholipid syndrome (APS) is a rare systemic autoimmune disease characterized by persistent antiphospholipid antibodies (aPL) in combination with recurrent thrombosis in the veins and/or arteries, obstetric morbidity, and various non-thrombotic associated complications. APS can be primary, as an isolated condition, or secondary in the context of another autoimmune disease, especially systemic lupus erythematosus. This comprehensive clinical review aims to summarize the current understanding of APS pathogenesis, diagnostic approaches, and treatment strategies for this unique clinical entity. Methods: A comprehensive review of the existing literature on APS was conducted, focusing on pathophysiological mechanisms, current diagnostic criteria, and therapeutic approaches. Results: APS pathogenesis involves complex interactions between aPL, phospholipid-binding proteins, and the coagulation cascade. Apart from the cardinal features of thrombosis and APS-related obstetric morbidity, APS is associated with a wide spectrum of clinical manifestations. Diagnosis remains challenging due to overlapping symptoms with other conditions, and clinicians should maintain a high index of suspicion in order to set the diagnosis. The recently published 2023 ACR/EULAR criteria although not definitive for clinical decision-making, these criteria offer clinicians a valuable tool to aid in determining whether further investigation for APS is warranted. Continued refinement of these criteria through ongoing feedback and updates is anticipated. Treatment strategies center on anticoagulation, but individualized approaches are necessary. Conclusions: Early diagnosis and multidisciplinary management of APS are critical to reducing morbidity and improving outcomes. Moreover, familiarization with the 2023 ACR/EULAR criteria is encouraged, recognizing that ongoing feedback and updates will contribute to their ongoing refinement and improvement. While VKAs remain the mainstay of treatment for most APS patients further research is needed to optimize treatment strategies and deepen our understanding of APS’s underlying disease mechanisms. Full article

Machine learning and artificial intelligence tools were used to investigate the discriminatory potential of blood serum metabolites for thromboembolism and antiphospholipid syndrome (APS). ¹H-NMR-based metabonomics data of the serum samples of patients with arterial or venous thromboembolism (VTE) without APS (n = 32), thrombotic primary APS patients (APS, n = 32), and healthy controls (HCs) (n = 32) were investigated. Unique metabolic profiles between VTE and HCs, APS and HCs, and between VTE and triple-positive APS groups were indicative of the significant alterations in the metabolic pathways of glycolysis, the TCA cycle, lipid metabolism, and branched-chain amino acid (BCAA) metabolism, and pointed to the complex pathogenesis mechanisms of APS and VTE. Histidine, 3-hydroxybutyrate, and threonine were shown to be the top three metabolites with the most substantial impact on model predictions, suggesting that these metabolites play a pivotal role in distinguishing among APS, VTE, and HCs. These metabolites might be potential biomarkers to differentiate APS and VTE patients. Full article

Antiphospholipid syndrome (APS) is a thrombo-inflammatory disease propelled by circulating autoantibodies that recognize cell surface phospholipids and phospholipid-binding proteins. APS is an autoimmune disorder associated with recurrent thrombosis of arterial or venous vessels and/or recurrent obstetric complications as miscarriages. APS can be divided into primary or secondary clinical syndrome because of the possible association with other autoimmune systemic diseases as systemic lupus erythematosus (SLE). Vitamin K antagonists remain the mainstay of treatment for most patients with APS and, based on current data, appear superior to the more targeted direct oral anticoagulants. However, the choice of the type of antithrombotic drug is based on the anamnesis of affected patients: patients with previous arterial or venous thrombosis may benefit from anticoagulants, while patients with previous obstetric diseases may benefit from aspirin, but several clinical exceptions may be evaluated. This short review is dedicated to underlining the main clinical evidence for patients affected by APS or CAPS (catastrophic antiphospholipid syndrome) in order to prevent recurrent thrombosis. Full article

Background/Objectives: Our aim was to validate the performance of the American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for antiphospholipid syndrome (APS), published in 2023, in an APS cohort. Methods: A total of 193 patients, 83 with APS (secondary APS, n = 45; primary APS, n = 38) and 110 without APS (systemic lupus erythematosus (SLE), n = 100; others, n = 10), were included in this study. The performance (sensitivity, specificity and area under the curve (AUC)) of the 2023 ACR/EULAR classification criteria for APS was evaluated and the agreement with the revised Sapporo criteria was compared using the kappa test. Results: In our cohort, the sensitivity and specificity of the 2023 ACR/EULAR classification criteria for APS were 73% and 94%, respectively (AUC: 0.836, 95% CI: 0.772–0.899), while the sensitivity and specificity of the revised Sapporo criteria were 66% and 98%, respectively (95% CI: 0.756–0.888). The performance of the two sets of criteria in our cohort was significantly consistent and significant (p < 0.001). When the sensitivity, specificity and ROC curve analysis were performed again by excluding livedo racemosa, the sensitivity of the new criteria in our cohort was 62% and the specificity was 100% (AUC: 0.813, 95% CI: 0.746–0.881). Conclusions: Although the newly published criteria broaden the scope of APS classification by including clinical findings other than thrombosis and obstetric criteria, their sensitivity in our cohort was low. On the other hand, we found that the specificity of the criteria in our cohort reached 100% when livedo findings were excluded. Full article

Background/Objectives: ACR/EULAR has recently developed new classification criteria for antiphospholipid syndrome (APS). The present study aims to analyze the impact of these new 2023 ACR/EULAR classification criteria in a cohort of pregnant women with primary APS. Methods: Retrospective cohort study of 93 consecutive pregnant women attending the Autoimmune Diseases Pregnancy Clinic, a multidisciplinary unit of a tertiary care teaching hospital, between 2005 and 2023. All of them fulfilled the Sydney classification criteria for APS. Women diagnosed with rheumatic autoimmune diseases other than APS were excluded. Results: Twenty-four out of ninety-three patients (25.8%) met the 2023 ACR/EULAR criteria for APS. Patients who met the new classification criteria were very similar to those who did not, except for being younger (p < 0.001), and had a lower number of clinical pregnancies (p = 0.004). The obstetric domain was clearly underrepresented in women who fulfilled the 2023 ACR/EULAR criteria (p < 0.001). Patients meeting the new classification criteria were primarily characterized by preterm births before 34 weeks due to severe placentation disorders (p = 0.004). Women with early and late fetal loss were significantly underrepresented (p < 0.0001 and 0.03, respectively). Nearly half of these patients had thrombocytopenia (p < 0.001). Serologically, these patients showed a higher frequency of persistent lupus anticoagulant (p = 0.02) and a lower frequency of IgM isotype antiphospholipid antibodies (p = 0.05). Conclusions: Almost three-quarters of the patients included in the study did not meet the 2023 ACR/EULAR criteria. Most patients who could not be classified according to these new classification criteria were those with early and/or late fetal deaths, as well as patients carrying only IgM aCL/AB2GPI antibodies. The high specificity of the 2023 ACR/EULAR criteria, restricted to severe placentation disorders, may leave the majority of patients with obstetric APS out of the new classification criteria. Full article

Catastrophic Antiphospholipid Syndrome (CAPS) is a rare complication that can occur in patients with Antiphospholipid Syndrome (APS). CAPS occurs even more rarely during pregnancy/puerperium and pregnant patients, even less likely to show cardiac involvement without signs of damage on ultrasound and angiography with non-obstructive coronary arteries. We present a case of a 26-year-old breastfeeding woman, the youngest described with CAPS and acute myocardial infarction, whose diagnosis was made with cardiac magnetic resonance imaging (CMRI). A literature review of pregnant patients with similar problems was performed. There are diagnostic and therapeutic difficulties in treating these patients. CMRI demonstrated a transmural late enhancement area. A combination of therapies led to rapid clinical improvement. CMRI is an underused tool that reaffirms the pathophysiology of CAPS and leads clinicians to the possibility of a diffuse thrombotic process. CAPS involves more organs with high mortality rates. CMRI could be optimized in order to reach an early diagnosis and the most effective treatment. This study provides real-world evidence of the feasibility of MRI in a primary care setting during pregnancy/puerperium. Evidence from this study may influence future APS screening and inform policymakers regarding the use of leading MRI technology in the detection of the thrombotic process in a primary care setting. Full article

Primary antiphospholipid syndrome (PAPS) is a systemic autoimmune disorder, characterised by consistently high levels of antiphospholipid antibodies, thrombosis, and/or pregnancy morbidity. Due to various suspected causes, deficient or insufficient levels of vitamin D in the serum have been reported in patients with PAPS; however, the reports have been sporadic and inconclusive. This systematic review and meta-analysis aimed to comprehensively evaluate the serum vitamin D levels in patients with PAPS compared to controls. A protocol was registered in PROSPERO (Registration No. CRD42019132128) and a systematic literature search was conducted through Google Scholar, PubMed, Web of Science, Scopus, and ScienceDirect databases without restricting language and year. Pooled prevalence, mean difference (MD), and odds ratio (OR) along with 95% confidence intervals (CI) were determined by using a random effects model. Study quality was assessed by the Joana Brigg’s Institute (JBI) protocol and publication bias was evaluated by a trim and fill funnel plot, Begg’s, and Egger’s tests. The pooled prevalence of vitamin D deficiency and insufficiency was found to be 32.2% [95% CI: 16.3–48.2] and 61.5% [95% CI: 40.2–82.8], respectively. Serum levels of vitamin D were considerably lower in the PAPS patients compared to controls (MD: −5.75, 95% CI: −9.73 to −1.77; p = 0.005). Multiple sensitivity analyses showed that the results remained statistically significant, demonstrating the robustness of this meta-analysis. No significant publication bias was detected in determining the MD of serum vitamin D levels in PAPS and controls. In conclusion, PAPS patients had greater rates of vitamin D deficiency or insufficiency, higher frequency of thrombosis, and lower serum vitamin D levels than healthy individuals. Full article

Antiphospholipid syndrome (APS) is a thromboinflammatory disorder caused by circulating antiphospholipid autoantibodies (aPL) and characterized by an increased risk of thrombotic events. The pathogenic mechanisms of these antibodies are complex and not fully understood, but disturbances in coagulation and fibrinolysis have been proposed to contribute to the thrombophilic state. This study aims to evaluate the role of an emerging hemostatic molecule, FXI, in the thrombotic risk of patients with aPL. Cross-sectional and observational study of 194 consecutive and unrelated cases with aPL recruited in a single center: 82 asymptomatic (AaPL) and 112 with primary antiphospholipid syndrome (APS). Clinical and epidemiological variables were collected. The profile of aPL was determined. Plasma FXI was evaluated by Western blotting and two coagulation assays (FXI:C). In cases with low FXI, molecular analysis of the F11 gene was performed. FXI:C levels were significantly higher in patients with APS than in patients with AaPL (122.8 ± 33.4 vs. 104.5 ± 27.5; p < 0.001). Multivariate analysis showed a significant association between symptomatic patients with aPL (APS) and high FXI (>150%) (OR = 11.57; 95% CI: 1.47–90.96; p = 0.020). In contrast, low FXI (<70%), mostly caused by inhibitors, was less frequent in the group of patients with APS compared to AaPL (OR = 0.17; 95%CI: 0.36–0.86; p = 0.032). This study suggests that FXI levels may play a causal role in the prothrombotic state induced by aPLs and holds the promise of complementary treatments in APS patients by targeting FXI. Full article

Introduction: Antiphospholipid syndrome (APS) is an autoimmune disease characterised by arterious and venous thrombosis, miscarriage, and the presence of antiphospholipid antibodies (aPL) in the blood. As we know, APS is also characterised by accelerated atherosclerotic degeneration with an increased risk of thrombosis in all blood vessels, including the carotid arteries. Carotid artery stenosis can manifest in many different ways. The aim of this study is to present the results of our multidetector computerised tomography angiography (MDCTA) analysis of the carotid arteries in patients with primary and secondary APS compared with a control group. Materials and Methods: This study examined 50 patients with primary antiphospholipid syndrome (PAPS) and 50 patients with secondary antiphospholipid syndrome (SAPS). The results were compared with a control group also comprising 50 patients. The groups were analysed with respect to age, sex and the presence of well-established risk factors for vascular disease. The study was conducted using MDCTA, where we analysed the quantitative and qualitative (morphologic) characteristics of carotid artery lesions. Results: Patients from the control group had significantly elevated levels of cholesterol and triglycerides in comparison with patients with PAPS and SAPS (p < 0.001 and p < 0.05). The results show that carotid artery lesions were significantly more common in patients with APS (PAPS, n = 40, CI95: 0.50–0.75, p = 0.0322 and SAFS, n = 54, CI95: 0.59–0.80, p = 0.0004) than within the control group (n = 23). There was a statistically significant difference between patients with APS and the control group with respect to lesions in the distal segments (n = 27, CI95: 0.67–0.95, p = 0.0001), bulbi and proximal segments (n = 21, CI95: 0.84–1.00, p = 0.000005). The number of patients with one lesion (L) (n = 27) was significantly greater than the number of those with three (n = 10, CI95: 0.56–0.86, p = 0.0051) or four (n = 3, CI95: 0.73–0.98, p = 0.00001) lesions. There were also more patients with two lesions (n = 24) than those with four (n = 3) (CI95: 0.71–0.97, p = 0.00005). Carotid artery stenosis was shown as a percentage of the carotid artery lumen diameter (%DS). Stenosis of up to 30%, was more common in patients in the PAPS group (n = 12) than in the control group (n = 3) (CI95: 0.52–0.96, p = 0.0201), while the SAPS group (n = 17) had an even larger disparity (CI95: 0.62–0.97, p = 0.0017). We observed a highly significant difference in the frequency of stenoses between 30% and 50% DS between the PAPS group (n = 24) and the control group (n = 7) (CI95: 0.59–0.90, p = 0.0023), as well as the SAPS group (n = 30) (CI95: 0.65–0.92, p = 0.0002). A qualitative analysis of plaque morphology revealed that patients with PAPS had significantly more soft tissue lesions (n = 23) compared with calcified lesions (n = 2) (CI95: 0.74–0.99, p = 0.00003), as well as more mixed plaques (n = 9) and calcified plaques (n = 2) (CI95: 0.48–0.98, p = 0.0348). Patients within the SAPS group had significantly more soft tissue (n = 35) than calcified lesions (n = 3) (CI95: 0.79–0.98, p = 0.00000021), as well as more mixed lesions (n = 21) compared with calcified (n = 3) (CI95: 0.68–0.97, p = 0.0002). Conclusions: Our study shows that subclinical manifestations of carotid artery lesions were more common in patients with APS. We came to the conclusion that MDCTA is an accurate diagnostic method because it is a safe method that provides us with a great quantity of accurate information about the characteristics of atheromatous plaques, which aids us in the further planning of treatment for patients with APS. Full article

The place of non-criteria antiphospholipid antibodies (aPLs) in the diagnosis of antiphospholipid syndrome (APS) is still debatable. The aim of this research was to evaluate the correlations between the titres of non-criteria aPLs (anti-phosphatidylethanolamine (aPE), anti-phosphatidylserine (aPS), and anti-prothrombin (aPT) antibodies), and the ones of the already studied criteria aPLs (anti-cardiolipin (aCL) and anti-β2 glycoprotein I-aβ2GPI antibodies). Altogether, 72 APS (30 primary and 42 secondary) patients were included in our study. High correlation coefficients (rs) were found between aPS IgM and aCL IgM, overall (0.77, p < 0.01), as well as in the primary (0.81, p < 0.01), and secondary (0.75, p < 0.01) APS subgroups. Low or statistically insignificant correlations were observed between IgG/IgM isotypes of aPT and aCL, or aβ2GPI, in the entire study population, and when evaluating the subgroups. Therefore, moderate correlations were mainly identified between the tested non-criteria antibodies and the criteria ones, suggesting little added value for the use of the tested non-criteria aPLs, with the exception of aPT, which seems to have different kinetics and might be a promising APS diagnostic tool. Full article

Primary antiphospholipid syndrome (PAPS) is a systemic autoimmune disease associated with recurrent thrombosis and/or obstetric morbidity with persistent antiphospholipid antibodies (aPL). Although these antibodies drive endothelial injury and thrombophilia, the underlying molecular mechanism is still unclear. Small extracellular vesicles (sEVs) contain miRNAs, key players in intercellular communication. To date, the effects of miRNA-derived sEVs in PAPS are not well understood. We characterised the quantity, cellular origin and miRNA profile of sEVs isolated from thrombotic APS patients (PAPS, n = 50), aPL-carrier patients (aPL, n = 30) and healthy donors (HD, n = 30). We found higher circulating sEVs mainly of activated platelet origin in PAPS and aPL patients compared to HD, that were highly engulfed by HUVECs and monocyte. Through miRNA-sequencing analysis, we identified miR-483-3p to be differentially upregulated in sEVs from patients with PAPS and aPL, and miR-326 to be downregulated only in PAPS sEVs. In vitro studies showed that miR-483-3p overexpression in endothelial cells induced an upregulation of the PI3K-AKT pathway that led to endothelial proliferation/dysfunction. MiR-326 downregulation induced NOTCH pathway activation in monocytes with the upregulation of NFKB1, tissue factor and cytokine production. These results provide evidence that miRNA-derived sEVs contribute to APS pathogenesis by producing endothelial cell proliferation, monocyte activation and adhesion/procoagulant factors. Full article