Thrombosis and haemostasis最新文献

Atrial fibrillation (AF) significantly increases the risk of ischemic stroke. This study evaluates whether transmitral atrial flow velocity (MVA), measured non-invasively via transthoracic echocardiography (TTE), predicts stroke risk in AF patients.To assess the independent association between TTE-derived MVA and stroke incidence in paroxysmal AF patients and its value in refining risk stratification, especially in low-risk groups.This cohort study included 10,150 paroxysmal AF patients from 2010 to 2021. The primary outcome was hospitalization for ischemic stroke. Multivariable Cox regression analyses adjusted for CHA₂DS₂-VASc scores evaluated the relationship between MVA and stroke risk.Over a mean follow-up of 4.26 ± 3.52 years, 2,419 (23.8%) patients developed ischemic strokes (5.59% per 100 person-years). In multivariable analysis, adjusting for CHA₂DS₂-VASc score, MVA was independently associated with stroke incidence. Every 10 cm/s reduction in MVA velocity conferred 4% higher stroke risk (adjusted hazard ratio [HR] 0.96 [0.94-0.97], P < 0.001). AF patients with MVA < 50 cm/s had a 39% increase in stroke risk compared to those with MVA ≥ 50 cm/s (adjusted HR 1.39 [1.22-1.58], P < 0.001). In patients with a CHA₂DS₂-VASc score of 0 or 1, the stroke incidence increased from 1.33 to 2.28% when they had MVA < 50 cm/s, which was similar to that of patients with a CHA₂DS₂-VASc score of 2 points (2.51%).TTE-derived MVA independently predicts stroke risk in paroxysmal AF patients. Incorporating MVA enhances risk stratification and guides targeted stroke prevention, particularly in low-risk populations.

To conduct an updated systematic review of the current evidence on the implementation of the 'Atrial fibrillation Better Care' (ABC) pathway for the comprehensive and holistic management of patients with Atrial Fibrillation (AF).We performed a systematic review and meta-analysis, searching MEDLINE and EMBASE for studies reporting the prevalence of ABC-adherent management in patients with AF and its association with clinical outcomes (all-cause death, cardiovascular death, stroke, stroke/thromboembolism (TE), and major bleeding). Random-effects models were used to pool results from individual studies; subgroup analyses and meta-regressions were also conducted.Overall, 22 studies were included (including 2 randomised trials), with >380,000 AF patients. Adherence to the ABC pathway was 23.9% (95%CI: 17.5%-31.7%), with substantial between-study heterogeneity (I²: 99.8%). Adherence was higher in European cohorts (37.9%, 95%CI: 27.8%-49.2%) and increased with advancing age. ABC pathway adherence was associated with a lower risk of all-cause death (Odds Ratio [OR]: 0.49, 95%CI: 0.41-0.58, I²: 97.1%), cardiovascular death (OR: 0.46, 95%CI: 0.36-0.59, I²: 96.4%), stroke (OR: 0.65, 95%CI: 0.51-0.82, I²: 93.5%), stroke/TE (OR: 0.53, 95%CI: 0.42-0.66, I²: 91.1%) and major bleeding (OR: 0.81, 95%CI: 0.69-0.94, I²: 89.2%). The effect of the ABC pathway was consistent in clinical trials versus real-world studies, but influenced by study-level characteristics, including geographical location, mean age, prevalence of comorbidities, and the inclusion of estimates adjusted for potential confounders.Adherence to the ABC pathway remains suboptimal in patients with AF, but is associated with substantial beneficial effects on prognosis. Our data support widespread implementation of the ABC pathway for managing patients with AF.

This article describes the SAFER (Screening for Atrial Fibrillation with ECG to Reduce stroke) programme that was established to determine whether intermittent screening for atrial fibrillation with a single-lead electrocardiogram reduces the risk of stroke and other key outcomes such as death, dementia and cardiovascular disease. The programme comprises feasibility studies, a pilot trial, a randomised controlled trial, qualitative studies and an economic analysis. Recruitment and screening for the trial have been completed, and it is anticipated that follow-up will finish in 2027.

Anti-CD36 isoantibodies can induce platelet transfusion refractoriness and fetal neonatal immune thrombocytopenia. However, the mechanism of platelet clearance mediated by these antibodies (Abs) in such disorders remains unknown.We analyzed platelet clearance caused by mouse and human CD36 monoclonal Abs GZ1 IgG1 and IgG2 subclasses in vitro and in vivo.Platelet clearance was evaluated in vitro by platelet phagocytosis assays and in vivo by monoclonal Ab GZ1 administration to C57BL/6J mice. Platelet activation, apoptosis, and desialylation were analyzed by flow cytometry.Both anti-CD36 Abs subclasses caused lower platelet clearance than anti-αIIbβ3 owing to the FcγR occupancy of monocytes by anti-CD36 Abs. This reaction could lead to mild thrombocytopenia, compared with the severe thrombocytopenia induced by anti-αIIbβ3 platelet-specific Abs. IgG subclass-mediated platelet clearance was inhibited by anti-FcγR Abs and intravenous immunoglobulin (IVIG). The human IgG2 Ab subclass caused lower platelet clearance than IgG1. IgG1- and IgG2-mediated platelet phagocytosis was inhibited by anti-FcγRI and anti-FcγRII, respectively. Unlike IgG1, the IgG2 Ab subclass induced platelet activation, apoptosis, and desialylation and platelet clearance by endothelial cells via Fc-independent pathway.IgG1 and IgG2 subclasses of anti-CD36 Abs triggered platelet clearance primarily via the Fc-dependent pathway. The IgG2 Ab subclass, however, additionally induced platelet clearance via the Fc-independent pathway. These results indicate that the anti-CD36 Ab IgG subclass influences platelet clearance efficiency and may therefore determine the severity of immune thrombocytopenia caused by anti-CD36 antibodies.

Direct oral anticoagulants (DOACs) are increasingly used for superficial vein thrombosis (SVT), yet evidence remains limited. This systematic review and meta-analysis synthesizes all available data on the efficacy and safety of DOACs in SVT.A systematic search identified randomized and observational studies enrolling adults with acute SVT treated with DOACs. Primary efficacy outcomes were venous thromboembolism (VTE: deep vein thrombosis or pulmonary embolism) and SVT recurrence/extension. Safety outcomes included major and clinically relevant non-major bleeding (CRNMB).Six studies (n = 2,040; 602 DOAC-treated patients) met the inclusion criteria. Compared with fondaparinux, DOACs showed comparable short-term efficacy for VTE prevention (pooled risk ratio [RR] 0.93, 95% CI 0.44-1.99) and similar rates of SVT recurrence (RR 1.30, 95% CI 0.65-2.62). Versus placebo, rivaroxaban reduced recurrence by approximately 80% (RR 0.20, 95% CI 0.03-1.35). In the pooled safety analysis including four studies, DOACs were associated with a 65% relative risk reduction in major or CRNMB compared with fondaparinux or low-molecular-weight heparin (RR 0.35, 95% CI 0.15-0.83; I ² = 0%). In the TROLL registry (n = 229; 74% DOAC), no major bleeding occurred among DOAC users, while 5-year cumulative VTE and SVT recurrence rates were each 15.9%. Certainty of evidence was moderate for efficacy and high for safety.DOACs demonstrate efficacy comparable to fondaparinux and an excellent safety profile in SVT, supporting their use as a practical oral alternative. Long-term data indicate persistent thrombotic risk, suggesting potential benefit of extended low-dose prophylaxis in selected high-risk patients.

Endothelial dysfunction is central to COVID-19 pathophysiology, contributing to vascular complications and disease progression. However, the mechanisms driving disease evolution and response to endothelial-targeted therapies remain unclear. This study characterizes endothelial activation throughout the course of acute COVID-19 and evaluates the response to potential therapeutic agents.Serum samples from patients admitted due to moderate to severe COVID-19 pneumonia were prospectively collected on three study time points (+1 day, +4 days and +10 days). Human microvascular endothelial cells were cultured in medium supplemented with pooled serum within the same disease stage, with or without defibrotide, apixaban, or tocilizumab. Endothelial activation was assessed by immunofluorescence and quantitative mRNA expression of adhesion molecules, extracellular matrix (ECM) proteins, and innate immunity receptors. ECM reactivity was evaluated using a platelet adhesion assay. Intracellular signaling pathways were analyzed by immunoblotting.One-hundred and two patients were included. Compared to healthy donor plasma, patient plasma induced upregulation of Vascular cell adhesion molecule-1, Toll-like receptor 4, and von Willebrand factor in endothelial cells. This effect decreased over admission days and in response to drugs. Similarly, ECM reactivity was highest at admission and declined as the disease progressed. Vascular-endothelial cadherin was mildly downregulated, but its expression was unaffected by drug treatment in vitro. Defibrotide mitigated COVID-19 serum induced p38MAPK and Erk activation but enhanced Akt phosphorylation.Serum from severe COVID-19 patients induces a proinflammatory and prothrombotic endothelial phenotype, which can be modulated by endothelial-targeted therapies. These findings support the potential clinical value of endothelial-directed treatments.

Atrial fibrillation (AF) is associated with an increased risk of stroke and hypercoagulability. Coagulation factors mediate remodeling processes via protease-activated receptors (PARs) in various organs.We evaluated whether inhibition of factor Xa (FXa) via rivaroxaban protects against atrial structural remodeling in goats with persistent AF and explored FXa and thrombin hypertrophic effect on human iPSC-derived cardiomyocytes (hiPSC-CMs).Three groups of goats were tested: CTRL AF (control AF, n = 10), RIVA AF (rivaroxaban treatment during AF, n = 11), and SHAM (no AF, n = 10). Pacing-induced AF was maintained for 16 weeks. AF stability, hemodynamics, and AF complexity were assessed. Atrial samples were collected for histological and gene expression analyses. hiPSC-CM were stimulated with PAR-1 agonist TRAP14, FXa, or thrombin with and without their inhibitors. Pro-hypertrophic and pro-inflammatory gene expression was assessed by qRT-PCR after 24 hours.Rivaroxaban inhibited thrombin generation in RIVA AF goats (baseline: 249 ± 42 nM vs. final: 69 ± 33 nM). Sixteen weeks of AF induced atrial myocyte hypertrophy in CTRL AF (13.5 µm [95% CI: 12.9, 14.0] vs. SHAM: 12.5 µm [95% CI: 12.0, 13.0]) and pro-hypertrophic (NPPA: fourfold; NPPB: 22-fold) and pro-fibrotic (COL1A1: threefold) gene expression. Rivaroxaban fully prevented hypertrophy (12.2 µm [95% CI: 11.7, 12.7]) and downregulated inflammatory signaling without altering hemodynamics and AF stability. In hiPSC-CM, thrombin and TRAP14 induced overexpression of the pro-hypertrophic genes NPPA and NPPB. The PAR1 antagonist, SCH79797, prevented thrombin-induced NPPA and NPPB upregulation.Prolonged rivaroxaban treatment reduces thrombin generation, preventing AF-induced atrial myocyte hypertrophy through inhibition of PAR-1 signaling.

To examine the impact of different therapeutic international normalized ratio (INR) ranges on anticoagulation control and clinical outcomes in patients with mechanical heart valves (MHVs) treated with vitamin K antagonists (VKAs) in the Netherlands.Data from 17 anticoagulation clinics (2013-2019) were linked to nation-wide data from Statistics Netherlands. Anticoagulation control metrics included significant dose adjustments, INR variance growth rate, and time in therapeutic range. Cause-specific Cox regression models were used to assess associations between therapeutic ranges and clinical outcomes, accounting for death as competing risk. Stratified analyses were performed for significant interactions by type of MHV recipient.Among 3,473 MHV patients (median age: 67.0 [IQR: 58.0-76.0], 61.7% male, 68.2% acenocoumarol, 26.5% phenprocoumon), patients with lower therapeutic ranges (N = 1,866) (2.0-3.0 for isolated aortic valve without risk factors; 2.5-3.5 for all remaining MHV patients) had poorer anticoagulation control compared to those with higher ranges (N = 1,607) (2.5-3.5 and 3.0-4.0, respectively). No association was found between therapeutic ranges and major/clinically relevant bleeding (fully adjusted hazard ratio [aHR]: 0.80 [95%CI: 0.57-1.1]). However, in patients with a non-aortic valve and/or additional risk factors a lower therapeutic range was potentially associated with increased thromboembolic risk (aHR: 1.3 [95%CI: 0.94-1.9]), while no association was observed in patients with an isolated aortic valve (aHR: 0.71 [95%CI: 0.38-1.3]).A lower therapeutic range does not apparently increase thromboembolic risk in most MHV patients but may be associated with a higher thromboembolic risk in higher risk patients. Lower therapeutic ranges were not associated with lower bleeding risk.