Thrombosis and haemostasis最新文献

Anti-Xa assays are seldom rapidly available, prompting clinicians to frequently administer four-factor-prothrombin complex concentrate (4F-PCC) empirically.Determine if the thrombotic risk increases when preoperative factor Xa inhibitor (XaI) levels are low or unmeasured.We analyzed retrospectively all patients who received 4F-PCC between September 2018 and July 2024 at five hospitals in the Hamilton region and screened for those with emergency surgery/invasive procedure as the main indication. The primary outcomes were symptomatic or asymptomatic, objectively verified arterial or venous thromboembolism within 7 days of 4F-PCC infusion. The secondary outcome was the same between postoperative days 8 and 30. XaI levels were determined with an anti-Xa assay, calibrated with the respective oral anticoagulant used by the patient.Four-F-PCC at a median dose of 2,000 units (interquartile range, 2,000-2,000) was administered to 227 patients on apixaban (143; 63%), rivaroxaban (72; 32%), or edoxaban (12;5%). The mean age was 76 years, and 42% were female. Prophylaxis against venous thromboembolism was started promptly in 214 patients (94%) after a median of 1 day (interquartile range, 1-2). Thromboembolism within 7 days occurred in 1 of 38 patients (3%) with high XaI level, 0 of 24 with low level, and 9 of 165 (5%) with no level.The risk of thromboembolism after 4F-PCC in patients on XaI and emergency surgery/invasive procedures appears to be similar among patients with preoperative XaI levels that are high, low, or not measured. This information might be helpful in settings where rapid anti-Xa testing is unavailable.

Von Willebrand Disease (VWD) is a common inherited bleeding disorder, arising from quantitative or qualitative defects in von Willebrand factor (VWF). Its wide phenotypic variability poses challenges for accurate diagnosis and subtype classification.The B-Will Study is a comprehensive analysis of VWD within the Belgian population, focusing on phenotypic and genotypic characteristics.Patients with suspected VWD were identified from historical records. Extensive laboratory phenotyping, including VWF multimer and genetic analysis, was performed in order to establish definitive VWD classification and subtyping.VWD was confirmed in 511 patients, with type 1 as the predominant subtype, followed by type 2 (especially, 2A/IIE and 2M-GPIbM). Laboratory phenotype and multimeric pattern were concordant in 75% of 323 cases. Genetic analysis revealed at least one causal variant in 92.7% of patients, uncovering 126 unique variants (58 novel variants). MLPA detected large gene deletions in cases lacking variants by direct sequencing, raising overall variant detection to 93.4%. Phenotype-genotype concordance reached 66% of the 247 fully characterized patients' subgroup.The B-Will Study significantly enhances understanding of VWD in Belgium, demonstrating that integrated phenotypic and genotypic evaluation improves diagnostic accuracy and subtype classification. The established VWD biobank provides a foundation for longitudinal studies, advanced genetic testing, and international collaboration to optimize VWD management.

Backgrounds: Congenital antithrombin (AT) deficiency, primarily caused by SERPINC1 variants, is a major risk factor for venous thromboembolism (VTE). We previously reported the SERPINC1 p.M313T variant in three VTE probands with normal AT activity and antigen levels. This study aims to elucidate its pathogenetic mechanism.

Methods: Thrombin generation test (TGT), thermal stability, native-urea PAGE, in vitro protein expression, and enzymatic assays were performed. Glycosylation analysis was conducted using glycosidase treatment, and structural analysis was performed through molecular dynamics simulation.

Results: AT in probands' plasma samples exhibited reduced thermostability and increased proportions of denatured and latent forms compared with normal pooled plasma. The recombinant AT-M313T protein exhibited increased inhibitory activity, consistent with findings in proband plasma based on AT activity and TGT. Despite this enhanced activity, the mutant protein demonstrated reduced thermostability and a marked tendency to transition into the latent form, potentially predisposing carriers to thrombosis under stress conditions. These characteristics may result from the introduction of abnormal O-linked glycosylation within the breach region, confirmed in both plasma-derived and recombinant AT. Molecular dynamics simulation revealed a less compact structure, with increased spacing in the shutter region and enhanced flexibility of the reactive center loop.

Conclusions: The SERPINC1 p.M313T variant exhibits dual characteristics of high inhibitory activity and low structural stability, which together contribute to the transient AT deficiency. These findings suggest that AT deficiency may be underdiagnosed and highlight the importance of integrating techniques such as native-urea PAGE into standard diagnostic workflows to identify variants associated with structural abnormalities.

The detection of atrial fibrillation (AF) after transient ischaemic attacks (TIA) is crucial for initiating effective secondary prevention using oral anticoagulation. The choice of the best method and the duration of ECG monitoring to detect AF is uncertain. ODEA-TIA is a multicentre, investigator-initiated, randomised, open-label, blinded-endpoint (PROBE) clinical trial designed to compare three ECG monitoring strategies for detecting AF in patients aged 50 years or older who experienced a TIA within 28 days before randomisation and had no prior history of AF. Participants are randomly assigned in a 1:1:1 ratio, stratified by age and centre, to undergo either 24-hour Holter ECG, 28-day non-invasive continuous ECG patch monitoring, or continuous recording with a subcutaneously implantable loop recorder for up to 2-years. The primary endpoint is the rate of newly detected AF within six months after study enrolment. Secondary endpoints include AF detection at 12 and 24 months, and overall prevalence of AF during follow-up in long-term recordings. Exploratory analyses include clinical outcomes, initiation of anticoagulation and performance parameters. A substudy investigates the usefulness of blood-based biomarkers to predict AF. ODEA-TIA aims to establish evidence-based ECG monitoring strategies for detection of AF to improve secondary prevention in TIA patients.

High-sensitivity cardiac troponin I (hs-cTnI) is frequently elevated in patients with pulmonary embolism (PE), although its prognostic value in hemodynamically stable cases and the optimal cutoff points for risk stratification remain unclear.This prospective observational study included consecutive patients with symptomatic, hemodynamically stable PE from 2018 to 2023 at a tertiary hospital. Hs-cTnI levels were measured at diagnosis, and sex-specific cutoff points were determined for a 30-day composite outcome, defined as PE-related mortality, non-PE-related mortality, hemodynamic instability, reperfusion treatment, or admission to the intensive care unit. The secondary outcome was to compare the clinical performance of the European Society of Cardiology (ESC) classification and the modified FAST score when applying sex-specific hs-cTnI cutoff points.Among the 720 patients included, 39.5% had elevated hs-cTnI levels, with a higher prevalence in women (49.1% vs. 30.4%). The composite outcome occurred in 8.4% of men and 7.1% of women. The optimal hs-cTnI cutoff points for predicting the primary outcome were ≥ 25 pg/mL in women and ≥ 50 pg/mL in men. Elevated hs-cTnI was independently associated with the composite outcome in the total sample, with consistent association in women (adjusted odds ratio [aOR]: 10.1, 95% CI: 2.1-48) and men (aOR: 9.8, 95% CI: 2.9-32.6). The ESC score preserved an optimal negative likelihood ratio of 0.This study identified sex-specific hs-cTnI cutoff points that improve the clinical performance while maintaining high negative predictive value and reducing false positives in hemodynamically stable PE.

Background: The left atrial (LA) morphological profile, anatomically contiguous with the left atrial appendage (LAA), exhibits hemodynamic properties associated with thrombogenic predisposition in nonvalvular atrial fibrillation (NVAF). Integrating these structural biomarkers with clinical parameters enables noninvasive predict thrombosis risk.

Methods and results: This single-center retrospective study analyzed 253 NVAF patients undergoing pre-ablation dual-phase delayed LA computed tomography angiography (CTA). A machine learning(ML) model incorporating clinical and radiomics features was developed to predict LAA thrombosis/blood stasis. Multi-framework interpretation revealed robust predictive performance: global accuracy 92%, thrombosis subgroup F1-score 0.97 (95%CI: 0.89-1.00) with Area Under the Curve 1.00 (AUC: 95%CI: 0.99-1.00), blood stasis subgroup F1-score 0.90 (95%CI: 0.81-0.97) with AUC 0.97. Model reliability was confirmed by Cohen's κ=0.88 and 5-fold cross-validation(CV) score (mean score 0.91, range 0.88-0.94). Contribution visualization analysis identified clinical parameters as primary predictors, with LA sphericity and radiomic texture features providing incremental calibration.

Conclusion: The multimodal model integrating clinical profiles with CTA-derived radiomics effectively stratifies LAA thrombosis and blood stasis risks, demonstrating a exceptional discriminatory accuracy for thrombus detection.

We investigated potential differences in arterial stiffness, thickness of endothelial glycocalyx, deformation of left atrium and ventricle among various ischemic stroke subtypes and controls.We included 194 ischemic stroke patients (n = 47 lacunar stroke, n = 50 large artery atherosclerotic stroke [LAA], n = 49 cardioembolic stroke, n = 48 with embolic stroke of undetermined source [ESUS]) and 50 matched controls. We measured: (1) perfused boundary region (PBR4-25) of the sublingual microvessels, (marker of endothelial glycocalyx integrity), (2) pulse wave velocity (PWV) and central systolic blood pressure (cSBP), (3) left ventricular global longitudinal strain, left atrial (LA) reservoir, conduction and contraction strain, (4) myocardial work indices, by pressure-myocardial loops, and (5) PWV/GLS ratio, to assess ventriculoarterial interaction.Compared with controls, stroke patients displayed affected LA strains, LVGLS, Wasted Work, PBR4-25, cSBP, PWV, and PWV/GLS (p < 0.05). We observed differences in LA strain, PWV, PWV/GLS, and PBR4-25 between different ischemic stroke subtypes (p < 0.05). Participants with lacunar strokes had the most impaired PBR4-25, participants with cardioembolic stroke and ESUS had the most impaired LA strain, and LAA had the most affected PWV and PWV/GLS (p < 0.05). PBR4-25 value of 2.29 μm could discriminate lacunar strokes (AUC: 0.81, 95% CI: 0.74-0.89; p < 0.001), PWV cut-off of 13 m/second could discriminate LAA (AUC: 0.80, 95% CI: 0.72-0.89; p < 0.001) and LA reservoir strain cut-off of 25% could discriminate ESUS/Cardioembolic strokes (AUC: 0.78, 95% CI: 0.71-0.85; p < 0.001).Lacunar strokes exert excessive shedding of endothelial glycocalyx, LAA show aggravated aortic stiffness, while ESUS/Cardioembolic strokes demonstrate worse LA performance. These differences in the underlying pathophysiological mechanisms among stroke subtypes may guide individualized secondary prevention strategies.

Thromboembolic cardiovascular diseases (CVD), including acute coronary syndromes, ischemic stroke, and venous thromboembolism, remain a leading cause of morbidity and mortality worldwide. Despite significant improvements in prevention and diagnosis, thromboembolic CVD remains a major global health challenge, reflecting the incomplete control of multifactorial vascular risk. Growing evidence indicates that air, noise, and light pollution are important yet underrecognized contributors to cardiovascular morbidity. Exposure to particulate matter (PM_2.5, PM₁₀), gaseous pollutants (NO₂, SO₂, CO, O₃), chronic noise, and artificial light at night promotes endothelial dysfunction, oxidative stress, inflammation, and platelet activation-key mechanisms fostering a prothrombotic setting. Although regulatory progress has been achieved, air pollution remains the most significant environmental determinant of cardiovascular health globally, and the combined effects of coexisting pollutants are not fully understood. The convergence of urbanization, industrialization, and increasing light exposure further amplifies environmental impacts on vascular health. This scientific statement aims to synthesize current epidemiological and mechanistic evidence, highlight the complex interactions among air, noise, and light pollution, identify critical research gaps, and provide a comprehensive conceptual framework for understanding how environmental stress contributes to thromboembolic cardiovascular complications. Strengthening multidisciplinary research, integrating exposome-based data, and implementing effective prevention policies are essential steps toward mitigating the cardiovascular burden of environmental pollution.