Search Results (270)

Objectives: Borrelia burgdorferi sensu lato, a spirochete bacterium responsible for Lyme borreliosis—the most common tick-borne infection in North America and Europe—can trigger the production of antiphospholipid antibodies. These antibodies target host lipids such as cardiolipin (CL), phosphatidic acid (PA), phosphatidylcholine (PC), and phosphatidylserine (PS), which the spirochete incorporates into its membrane from the surrounding environment. Although antiphospholipid antibodies are typically associated with antiphospholipid syndrome (APS), they may also arise during infections, including Lyme borreliosis. This study aimed to develop and optimize several enzyme-linked immunosorbent assays (ELISAs) for measuring various antiphospholipid antibodies in patients with Lyme borreliosis. Methods: Thirty patients diagnosed with Lyme borreliosis were enrolled: ten with solitary erythema migrans (EM), ten with multiple EM (MEM), and ten with late manifestations known as acrodermatitis chronica atrophicans (ACA). Forty healthy blood donors served as controls. Four distinct antiphospholipid antibody ELISAs were developed, each using a different phospholipid coating: CL, PA, PC, and PS. Serum of APS patient was used as a positive control and for standard curve generation. Results: All four ELISAs were successfully established and demonstrated good measurement precision. Significant differences in antiphospholipid antibody levels and positivity rates were observed between Lyme borreliosis patients and healthy blood donors. Notably, levels of antibodies directed against PA (aPA), PC (aPC), and PS (aPS), both IgG and IgM, were significantly higher in patients with late Lyme borreliosis, manifested as ACA, compared to healthy blood donors. In contrast, anti-CL (aCL) levels did not differ significantly between groups. Patients with ACA also showed the highest frequency of multiple antiphospholipid antibody positivity, with 7 out of 10 patients testing positive for three or more antiphospholipid antibodies. Conclusions: Accurate and precise in-house ELISAs for the detection of aCL, aPA, aPC, and aPS using APS sera as standard material were developed and validated for the analysis of samples of patients with Lyme borreliosis. Our data suggest that antiphospholipid antibody levels—specifically aPA, aPC, and aPS—differ across clinical manifestations of Lyme borreliosis, with the greatest increases observed in patients with ACA. Full article

Antiphospholipid syndrome (APS) is a systemic autoimmune disorder driven by antiphospholipid antibodies (aPLs), primarily characterized by recurrent thrombosis and pregnancy morbidity. Transcriptomic analyses of other immune compartments have provided insights into APS pathogenesis. However, despite the central role of platelets in APS pathophysiology, their transcriptomic features remain largely unexplored. We therefore aimed to characterize the platelet transcriptomic landscape in APS and identify key immune-thrombotic pathways. RNA sequencing and bioinformatic analyses of platelets from 43 APS patients, 20 asymptomatic aPL carriers, and 20 healthy controls revealed distinct proinflammatory transcriptional reprogramming, consistent with platelets as active thrombo-inflammatory hubs. APS platelets exhibited marked activation of innate immune (Toll-like and NOD-like receptors) and neutrophil pathways, which may contribute to disease propagation through a functional platelet–neutrophil axis. A 15-gene classifier (e.g., FCER1G, MAP4K4) discriminated APS from controls with high accuracy (Area Under the Curve 0.901–0.948). The classifier also highlighted molecular differences between APS and asymptomatic aPL carriers relevant to disease progression. Network analysis suggested that anti-β2-glycoprotein I antibodies were associated with unique coagulation–immunity modules, while arterial and venous thrombosis displayed divergent cytoskeletal-energetic and lipid-signaling signatures, respectively. Together, these findings suggest that platelets in APS acquire a distinct proinflammatory phenotype and function as key immunothrombotic interfaces, supporting disease stratification and platelet-derived diagnostic strategies. Full article

Background/Objectives: To determine whether obstetric antiphospholipid syndrome (oAPS) among women with primary thrombotic APS (tAPS) defines a distinct immunologic phenotype or influences thrombotic characteristics and recurrence risk. Methods: This predefined subgroup analysis was conducted within a multicenter retrospective cohort study of 663 patients with persistent antiphospholipid antibody (aPL) positivity and objectively confirmed thrombosis. The present analysis included 295 women with primary tAPS and a history of pregnancy. Participants were classified as oAPS or non-oAPS according to the revised Sydney criteria. Demographic, clinical, obstetric, immunologic, and hematologic features at baseline were compared. Univariable and multivariable logistic regression analyses were performed to identify predictors of oAPS and determinants of arterial versus venous thrombosis. Results: Of 295 women, 115 (39.0%) met oAPS criteria. ANA positivity (33.0% vs. 19.0%, p = 0.008), triple aPL positivity (46.0% vs. 29.1%, p = 0.003), and severe thrombocytopenia (22.8% vs. 13.3%, p = 0.035) were more frequent in oAPS. In multivariable analysis, ANA positivity remained independently associated with oAPS (adjusted OR 1.94, 95% CI 1.05–3.56; p = 0.033), whereas triple aPL positivity and thrombocytopenia did not remain independently significant after adjustment. Thrombotic phenotype and recurrence rates were similar between oAPS and non-oAPS groups. Obstetric history was not associated with arterial events; hypertension was the strongest predictor of arterial thrombosis (adjusted OR 2.61, p < 0.001). Conclusions: In primary tAPS, oAPS is associated with features suggestive of an immune-enriched phenotype, particularly ANA positivity, without evidence of a distinct thrombotic phenotype or increased recurrence risk. Integration of obstetric and immunologic features may help guide risk stratification and hypothesis generation for future studies. Full article

Background: Antiphospholipid antibodies (aPLs) are essential for antiphospholipid syndrome (APS) diagnosis, which is based on clinical and laboratory parameters, including the detection of lupus-anticoagulant (LAC), anti-cardiolipin (aCL) and anti-β2-glycoprotein-I (aβ2-GPI) antibodies. The enzyme-linked immunosorbent assay (ELISA) is the reference methodology for classification criteria, although chemiluminescence immunoassays (CLIA) are more common in clinical practice. Methods: Since LAC reflects the functional activity of a large subset of antiphospholipids, through coagulation assays that enhance a phospholipid-dependent inhibitory effect, it has been used as a reference for assessing ELISA and CLIA reliability. Samples, separated into positive and negative LAC, were selected by CLIA detection in negative and positive IgG/IgM aCL and aβ2-GPI (cut-off > 20 U/mL). Results: The ELISA/CLIA comparison showed a 100% concordance in triple negative groups, highlighting an optimal analytical specificity; a higher concordance in the aβ2-GPI IgM-positive groups compared to positive aCL IgM (100% vs. 76% in LAC-positive groups; 82% vs. 71% in LAC-negative groups), as well as in aβ2-GPI IgM-negative groups compared to negative aCL IgM in LAC-positive groups (100% vs. 87.5%); and a massive concordance reduction in positive IgG aβ2-GPI and aCL groups (44% vs. 50% in LAC-positive groups; 4.8% vs. 4.5% in LAC-negative groups). Concordance increased in all groups with a higher CLIA cut-off (>50 U/mL). Conclusions: Although CLIA performances partly differed from ELISA, this does not preclude their use in APS diagnosis, which aims for higher sensitivity in detecting cases of disease. ELISA is confirmed to be more reliable for classification criteria that aim for high specificity to reduce false positives. Full article

Background: Recurrent pregnancy loss (RPL) remains etiologically unexplained in 40–50% of cases following standard diagnostic workup. Non-criteria antiphospholipid antibodies (non-criteria aPL) are increasingly considered potential markers of seronegative obstetric antiphospholipid syndrome (APS); however, their diagnostic value in this clinical setting requires further investigation. Objective: To assess the diagnostic value of non-criteria aPL in women with RPL and to construct an exploratory immunological scoring model for diagnostic stratification. Methods: Antiphospholipid antibody detection was performed using a single-measurement semi-quantitative line immunoblot assay (Anti-Phospholipid 10 Dot, Generic Assays, Germany). Statistical analysis included χ², Fisher’s exact test, Mann–Whitney U test, binary logistic regression, and ROC analysis. Results: Statistically significant associations with RPL were observed for anti-prothrombin antibodies (OR = 11.1; 95% CI 1.8–68.0; p = 0.022 [Haldane–Anscombe correction]), anti-annexin V (OR = 4.28; 95% CI 1.18–15.6; p = 0.023), and anti-β₂GP I (OR = 3.31; 95% CI 1.18–9.28; p = 0.019). The exploratory composite immunological score demonstrated moderate discriminatory performance (AUC = 0.701; 95% CI 0.588–0.814; p = 0.005). The overall logistic regression model was statistically significant (χ² = 8.564; p = 0.036), although none of the individual predictors retained independent significance, indicating a contribution of cumulative immunological burden rather than any single marker. Conclusions: In this single-center cross-sectional study, non-criteria aPL were frequently detected in women with RPL and were statistically associated with the condition. The findings should be interpreted as hypothesis-generating only, given the cross-sectional design, single-measurement immunoblot, small control group, and absence of external validation. Confirmation in larger prospective multicenter cohorts using ELISA-based assays with the internationally recommended 12-week repeat measurement is required before any clinical implementation. Full article

This study aimed to evaluate whether serum from patients with primary antiphospholipid syndrome (APS) is associated with changes in the expression of long non-coding RNAs (lncRNAs) in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were cultured with serum from 12 female patients with APS or 8 age-matched healthy female controls. The expression levels of HIF1A-AS1, OIP5-AS1, and GAS5 were quantified by RT-qPCR. Exposure of HUVECs to APS serum was associated with reduced expression of HIF1A-AS1 and OIP5-AS1 compared with cells stimulated with control serum. The median HIF1A-AS1 expression levels were 0.08 a.u. (interquartile range, 0.06–0.10) in APS-stimulated cells versus 0.14 a.u. (0.08–0.16) in controls (p = 0.044). Likewise, OIP5-AS1 levels were 0.09 a.u. (0.01–0.16) in APS-stimulated cells versus 2.24 a.u. (0.70–3.55) in controls (p = 0.018). In contrast, GAS5 expression did not differ significantly between groups (340 a.u. (310–3940 versus 358 a.u. (163–445); p = 0.290). In this proof-of-concept study, serum from APS patients was associated with selective downregulation of HIF1A-AS1 and OIP5-AS1 in endothelial cells. These findings support a potential link between circulating APS-related factors and endothelial lncRNA expression; however, no mechanistic or functional conclusions can be drawn. Full article

Pathologic pregnancies including recurrent pregnancy loss, stillbirth, early-onset pre-eclampsia and early-onset fetal growth restriction form a continuous spectrum throughout gestation and have attracted wide attention. Autoimmune disorders and associated acquired thrombophilia are key etiological factors. However, because of the complicated associations between various clinical manifestations, laboratory examinations and treatments, the management of pathologic pregnancies with autoimmune disorders and associated acquired thrombophilia are difficult. This viewpoint article presents a comprehensive full gestation management strategy emphasizing early identification and multidisciplinary management to improve pregnancy outcomes in these patients. Future research should focus on novel biomarkers, therapeutic methods and crosstalk mechanisms between autoimmune disorders and thrombophilia to optimize clinical strategies. Full article

Background/Objectives: Long-term outcomes in systemic lupus erythematosus (SLE) are largely driven by irreversible organ damage, yet the relative contribution of comorbid conditions remains insufficiently characterized. We aimed to characterize damage accrual and identify comorbidities associated with damage severity and mortality. Methods: A retrospective study of adult patients with SLE followed at a single-center (2014–2023). The Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), was used to assess damage at last follow-up. Damage was categorized as none (0), mild–moderate (1–2), or severe (≥3). Demographic, clinical, laboratory, treatment, and comorbidity data were extracted from electronic medical records. Multivariable logistic regression and Cox proportional hazards models were applied to identify factors associated with damage severity and mortality. Results: Among 182 patients (84.1% female; mean follow-up 15.6 ± 11.4 years), 59.5% accrued damage, including 30.8% with severe damage. Damage predominantly involved cardiovascular, ocular, neuropsychiatric, and musculoskeletal domains. It was associated with older age, longer disease duration, hematologic and renal involvement, and corticosteroids and immunosuppressive medications. In multivariable analysis, antiphospholipid syndrome (APS) and hypertension emerged as the dominant independent predictors of damage accrual with an odds ratio of 15.70 (95% CI 4.26–57.89, p < 0.001) and 6.46 (95% CI 2.54–16.40, p < 0.001), respectively. Mortality increased with damage severity (16.1% in SDI ≥ 3, 1.9% in SDI 1–2, none in SDI = 0; p < 0.0001). Damage was also associated with increased hospitalizations. Conclusions: Damage accrual is common and strongly predicts mortality. APS and hypertension emerge as dominant, modifiable drivers, supporting integrated cardiovascular and thrombotic risk management in SLE. Full article

Background: Elevated anticardiolipin IgG (aCL IgG) has been reported in end-stage renal disease (ESRD), but its association with specific etiologies of kidney failure remains unexplored. The unique pathophysiology of diabetic–hypertensive nephropathy may be associated with a microenvironment that could potentially contribute to antiphospholipid antibody production and thrombotic complications. This study aimed to investigate whether aCL IgG elevation in hemodialysis (HD) patients is associated with combined diabetes–hypertension (DM + HTN) etiology and thrombocytopenia, thereby identifying a clinically distinct potential high-risk subgroup. In this hypothesis-generating study, we focused on within-HD patient comparisons rather than healthy controls. Methods: We enrolled 242 participants: 150 healthy controls (included only to establish local reference ranges) and 92 patients with maintenance HD. The study was conducted from 01 September to 20 November 2025 in Madinah, Saudi Arabia. Serum aCL IgG was measured by chemiluminescence immunoassay (positive ≥ 12 GPL units). Comprehensive hematological and biochemical parameters were analyzed. Multivariable logistic regression identified predictors of aCL positivity. Results: In the HD cohort, 21% demonstrated aCL positivity; this represents a substantially higher rate than the 2% observed in local healthy controls (p < 0.001). This elevation was not uniform across etiologies. Strikingly, 94.7% (18/19) of aCL-positive HD patients had DM + HTN aetiology, compared with only 17.8% of aCL-negative patients (p < 0.001). Thrombocytopenia was significantly more severe in aCL-positive patients (median platelets: 100 vs. 191 × 10⁹/L, p < 0.001). In multivariable analysis, DM + HTN etiology (HTN-alone vs. DM + HTN odds ratio [OR]: 0.0013, 95% confidence interval [CI]: 0.00002–0.0999, p = 0.003; confirmed by Firth’s penalized logistic regression sensitivity analysis, and lower platelet count (OR: 0.92 per 1 × 10⁹/L increase, 95% CI: 0.87–0.98, p = 0.006) independently predicted aCL positivity. Conclusions: These hypothesis-generating findings suggest a potential association between metabolic–vascular disease and antiphospholipid immunity in ESRD. Causality cannot be inferred from this cross-sectional design. At present, routine aCL screening is not recommended outside of research protocols; prospective studies are needed to confirm these associations. Full article

Background: Vestibular symptoms and objective vestibular dysfunction have been reported in patients with autoimmune and rheumatologic diseases, but available evidence remains fragmented and methodologically heterogeneous. Previous studies have often addressed audiovestibular involvement as a combined entity, limiting disease-specific interpretation of vestibular outcomes. Methods: A PRISMA 2020-based systematic review was conducted using predefined eligibility criteria targeting vestibular outcomes in autoimmune and systemic rheumatologic diseases. Observational studies reporting vestibular symptoms and/or objective vestibular test results were included. Vestibular data were extracted even when studies reported combined audiovestibular outcomes. Certainty of evidence was assessed using the GRADE approach. Results: Twenty-seven studies were included in the qualitative synthesis, comprising 14 primary observational studies and 13 reviews. Vestibular involvement was reported across multiple diseases, including systemic sclerosis, giant cell arteritis, ankylosing spondylitis, psoriatic arthritis, Behçet disease, primary Sjögren syndrome, rheumatoid arthritis, systemic lupus erythematosus, antiphospholipid syndrome, and vasculitic disorders. Objective vestibular abnormalities were most frequently identified using caloric testing, balance integration measures, videonystagmography, and video head impulse testing. Systemic sclerosis and giant cell arteritis showed more consistently reported vestibular findings, although heterogeneity in assessment methods precluded quantitative synthesis. Conclusions: Vestibular involvement occurs across autoimmune and systemic inflammatory diseases, but overall certainty of evidence remains limited. Standardized vestibular assessment and longitudinal studies are needed to better define disease-specific vestibular phenotypes. Full article

Background/Objectives: Systemic lupus erythematosus (SLE) is frequently accompanied by psychological distress. Alexithymia, an impairment in identifying and describing emotions, has been reported in SLE, but its clinical and serological correlates remain insufficiently characterized. We aimed to estimate the prevalence of clinically significant alexithymia in SLE and to explore its clinical, laboratory, and coping-related correlates. Methods: In this cross-sectional observational study, adult outpatients fulfilling the 2019 ACR/EULAR SLE classification criteria were assessed at a tertiary referral centre (2024–2025). Alexithymia was measured using the Toronto Alexithymia Scale-20 (TAS-20), and clinically significant alexithymia was defined as a total score >60. Coping strategies were assessed with the 60-item COPE inventory (Italian version). Clinical indices (SLEDAI-2K, Lupus Low Disease Activity State (LLDAS), and SLICC/ACR Damage Index (SDI)), organ involvement, antiphospholipid syndrome (APS), selected autoantibodies, complement levels, and treatments were recorded. Group comparisons and exploratory logistic regression were performed. Results: Sixty-eight patients were included (94.1% female). Clinically significant alexithymia was present in 23.5%. In univariate analysis, alexithymia was more frequent among patients with APS. Alexithymic participants reported higher use of emotional venting and lower use of positive reinterpretation. In an exploratory multivariable logistic regression model, APS (adjusted OR 35.79, 95% CI 3.74–341.7), emotional venting (adjusted OR 1.684, 95% CI 1.162–2.44), and positive reinterpretation (adjusted OR 0.514, 95% CI 0.349–0.755) remained associated with alexithymia. Conclusions: Alexithymia was frequent in this SLE cohort and, in exploratory analyses, was associated with APS and specific coping patterns. These findings suggest that assessment of emotional processing and coping may provide complementary clinical information, particularly in patients with APS, but should be interpreted as associative and hypothesis-generating. Full article

Objective: Systemic lupus erythematosus (SLE), Sjögren syndrome (SS) and antiphospholipid syndrome (APS) are common autoimmune conditions in child-bearing aged women, but their influence on pregnancy and assisted reproductive outcomes remain controversial. We aimed to perform an umbrella review to summarize the current evidence to provide a reference for clinicians and future research. Methods: PubMed, Embase (Ovid) and Cochrane database were searched (inception to April 2025) for relevant publications. Study selection, data extraction, quality evaluation, evidence grading and data synthesis were completed independently by two authors. Odds ratio, relative risk or standardized mean difference with 95% confidence intervals were calculated. Results: Fourteen articles (51 meta-analyses) were included, to report the associations of SLE, primary SS (pSS), antiphospholipud antibodies (aPLs), primary APS (pAPS) and 6 maternal/8 fetal/5 assisted reproductive outcomes. SLE and pAPS significantly increased the risks of spontaneous abortion, total fetal loss, pregnancy-induced hypertension, premature delivery, small for gestational age, neonatal death and neonatal intensive care unit. SLE also decreased anti-Müllerian hormone level and significantly increased the risks of pre-eclampsia (PE), stillbirth, low birth weight (LBW) and neonatal one minute Apgar < 7. pSS significantly increased spontaneous abortion and LBW risks. Positive aPLs significantly increased the risk of miscarriage rate in assisted reproductive techenology (ART) and were also associated with total fetal loss, PE, intrauterine growth retardation and placental abruption. Conclusions: This review offers a thorough overview of the current evidence linking SLE, SS and APS to pregnancy and assisted reproductive outcomes. It identifies existing gaps and proposes future research directions. Full article

Background: Anemia is common among patients with antiphospholipid syndrome (APS). It can persist alone (primary APS—pAPS) or with another associated disease (secondary APS—sAPS), predominantly systemic lupus erythematosus (SLE). There are no systematic reviews addressing the type of anemia (iron deficiency without anemia—IDWA, iron deficiency—IDA, and anemia of chronic disease—ACD) in these patients. Objectives: This study aimed to assess the type of anemia and to compare the usefulness of common diagnostic anemia parameters and their mutual relations. Methods: A cross-sectional study involving 163 patients was conducted at the University Clinical Center Bezanijska kosa from June 2022 to June 2024, including 79 patients with pAPS, 47 with sAPS and 37 patients diagnosed with SLE. We compared the usefulness of iron metabolism markers (serum iron—Fe; total iron-binding capacity—TIBC; ferritin; hepcidin) in the presence of inflammatory markers such as high-sensitivity (hsCRP) and IL6 in determining the type of anemia. Results: The most common types were IDA (61.9%) and IDWA (64.3%) in pAPS patients. In contrast, ACD was equally distributed across the three groups, with prevalences of 32%, 32%, and 36% (pAPS, sAPS, and SLE, respectively). A higher frequency of thrombosis was significantly associated with a high ferritin level ≥100 (p = 0.017) and high IL6 levels (p = 0.033) as well as fetal losses (p = 0.034 and p = 0.019, respectively). The logistic regression model identified ferritin as the only significant predictor of IDA (p = 0.023). For IDWA, both ferritin (p = 0.017) and hepcidin (p = 0.038) were significant predictors of this type of iron depletion. IL-6 levels were significantly correlated with ferritin and hsCRP levels (p = 0.004 and p = 0.007, respectively). In contrast, hepcidin did not show a statistically significant correlation with inflammatory markers. A total of 40% of patients with IDA had hepcidin levels below 10, and 48% of those with ACD had hepcidin levels above 10 (p = 0.036). Conclusions: It was found that iron deficiency anemia was the most common form in pAPS, while anemia of chronic disease was equally present across all patient groups. Ferritin emerged as an independent marker for identifying iron deficiency anemia in APS patients. Although hepcidin reflects a low-inflammatory state in APS, it proved to be a more valuable tool than ferritin in distinguishing the type of anemia, especially when ferritin levels were inconclusive. Clinical manifestations in APS patients correlated with inflammatory markers. Liver function or any drug used alone or in combination had no impact on anemia type. Full article

Background/Objectives: Venous thromboembolic disease (VTE) is the most common initial manifestation of antiphospholipid syndrome (APS). Determining which patients with VTE to test for APS can be a challenging clinical decision. We aimed to determine if patients with APS present with more significant venous thromboembolic clot burden, as compared to patients with VTE without a diagnosis of APS. Methods: A multi-hospital single-institution retrospective cohort study was designed. Patients with a diagnosis of VTE who had been tested for APS from 1 December 2019 to 31 January 2022 were included. Patients were stratified based on the presence of APS (APS versus non-APS). Significant venous thromboembolic clot burden was defined as PE involving the main and/or lobar pulmonary arteries or DVT involving the iliofemoral veins. Assessment of clot burden was performed by review of radiology reports of the index clotting event. Results: We included 748 patients with a history of VTE who had been tested for APS; 75 patients (10%) were positive for APS. Significant clot burden was present in 29 (38.7%) APS patients and 269 (40.0%) non-APS patients (OR 0.95, 95% CI 0.58–1.56; p = 0.85). No predictors for significant clot burden were found on multivariable analysis. Triple-positive APS (OR 0.83, 95% CI 0.16–4.21; p = 0.82) and primary APS (OR 0.72, 95% CI 0.15–3.45; p = 0.68) were not associated with more significant clot burden. Conclusions: This retrospective single-institution analysis suggests that patients with APS may not present with more significant venous thromboembolic clot burden than patients with VTE without APS. Full article

Acute coronary syndrome (ACS), driven by inflammation and thrombosis, remains a leading cause of morbidity globally. While traditional risk scores are useful, the prognostic value of combining inflammatory and autoimmune biomarkers remains understudied. This study aimed to evaluate the predictive role of high-sensitivity C-reactive protein (hs-CRP), platelet factor 4 (PF4), D-dimer, and antiphospholipid antibodies (anticardiolipin and anti-β2-glycoprotein I) for the development of major adverse cardiovascular events (MACE) in patients with ACS. We conducted a prospective cohort study at a tertiary referral center in Mexico. A total of 103 patients admitted with confirmed ACS were included. Blood samples were collected upon admission to measure biomarker levels. Participants were followed for 30 days. The primary outcome was the occurrence of MACE, defined as reinfarction, death, percutaneous coronary intervention, or bypass surgery. Multivariate logistic regression analysis was performed to identify independent predictors, adjusting for age, smoking, and comorbidities. MACE occurred in 51.4% of participants. Patients with adverse outcomes were significantly older and had longer hospital stays (p < 0.05). In the biomarker analysis, PF4 and hs-CRP demonstrated high sensitivity (98%) but low specificity. In the multivariate analysis, IgG anti-β2-glycoprotein I (p < 0.001) and D-dimer (p = 0.024) emerged as significant independent predictors of MACE. Conversely, IgM isotypes did not show independent predictive value. Beyond traditional risk factors, markers of coagulation (D-dimer) and autoimmunity (IgG anti-β2-glycoprotein I) are independent predictors of short-term adverse events in ACS patients. Integrating these multidomain biomarkers into clinical assessment may enhance risk stratification and prognostic accuracy. Full article