Thrombosis and haemostasis最新文献

While resting heart rate (RHR) is associated with multiple diseases, conflicting information exists on the association between RHR and venous thromboembolism (VTE). We, therefore, aimed to investigate the association between RHR and risk of VTE in a population-based cohort.Participants (n = 36,395) were followed from inclusion in the Tromsø 4 to 7 surveys (1994-2016) throughout 2020. RHR was measured in beats per minute (bpm) at each survey (repeated measurements for those attending several surveys). All first-time VTEs during follow-up were recorded. Hazard ratios (HR) for VTE with 95% confidence intervals (CIs) according to RHR categories (61-70, 71-80, and >80 bpm) with ≤60 bpm as reference were estimated using Cox regression models, and adjusted for age, sex, body mass index, cardiovascular disease, cancer, and physical activity. We also performed age-stratified analyses (<60 and ≥60 years).During a median of 6.6 years of follow-up, 1,072 participants experienced a VTE. Fully adjusted HRs (95% CI) for overall VTE were 1.12 (0.93-1.35), 1.35 (1.11-1.63), and 1.19 (0.97-1.47) for RHR categories 61 to 70, 71 to 80, and >80 bpm, respectively. Corresponding HRs for unprovoked VTE were 1.56 (1.14-2.14), 1.76 (1.28-2.43), and 1.60 (1.13-2.25), whereas no association was observed for provoked VTE. The association was more consistent in those ≥60 years, with HRs for overall VTE, >80 bpm versus ≤60 bpm of 1.30 (1.02-1.65) and for unprovoked VTE of 1.86 (1.24-2.81).Our findings suggest that higher RHR may be a risk factor for VTE and more consistently so for those ≥60 years. The VTE risk by higher RHR was particularly pronounced for unprovoked events.

F11Receptor/junctional adhesion molecule-A (F11R/JAM-A) is a transmembrane protein expressed in endothelial cells, epithelial cells, and in blood platelets. In blood platelets, F11R/JAM-A participates in adhesion under static conditions, suppresses the activation of the platelet α_IIbβ₃ integrin and was shown to activate blood platelets as soluble form via homophilic interactions.The purpose of presented study was to evaluate whether F11R/JAM-A is involved in platelet adhesion under flow conditions and in thrombus formation.F11R/JAM-A contribution to platelet adhesion under flow conditions was assessed using flow chamber assay. Monoclonal antibodies and recombinant F11R/ JAM-A were used to assess the effects of F11R/JAM-A blockade on platelet aggregation and thrombus formation using total thrombus formation analysis system. Effects of F11R/JAM-A blockade on thrombus formation in vivo were evaluated in murine models of carotid artery injury.F11R/JAM-A was not capable of capturing flowing blood platelets alone but enhanced platelet adhesion to fibrinogen under flow conditions. Blocking of F11R/JAM-A homophilic interactions with specific monoclonal antibodies or with recombinant F11R/JAM-A impaired thrombus formation in vitro in human blood and in vivo in the models of thrombosis in mice.Interactions of F11R/JAM-A located on flowing platelets with its surface-bound counterpart enhance platelet binding to fibrinogen under high shear stress conditions. Blocking of these homophilic interactions compromises thrombus formation. While previously published studies pointed at a significant role of soluble F11R/JAM-A in priming platelets during thrombus formation, our results highlight the role of surface-bound F11R/JAM-A in this process.

Patients with spontaneous intracerebral hemorrhage (ICH) are at high risk of venous thromboembolism (VTE). Recent studies have shown the involvement of neutrophil extracellular traps (NETs) in thrombogenesis.To explore the predictive value of serum MPO-DNA (a NETs surrogate) for VTE and the effect of statins on serum MPO-DNA levels and the VTE incidence in ICH patients.This prospective cohort study enrolled 117 ICH patients and 15 healthy controls. Serum MPO-DNA levels were measured via ELISA. The relationship between serum MPO-DNA levels and VTE risk was analyzed. The predictive value of MPO-DNA was evaluated by ROC curves. Effects of statin on NETs and VTE incidence were evaluated.The median MPO-DNA level in patients with VTE was 0.304 (95% CI: 0.231-0.349), significantly higher than the 0.188 (95% CI: 0.159-0.236) in non-VTE patients. Elevated MPO-DNA levels were associated with an increased VTE risk (OR 7.13, 95% CI 2.58-19.75; P < 0.001), and this association persisted after adjustment. The AUC values for MPO-DNA, CRP, and D-dimer were 0.824 (95% CI: 0.719-0.928), 0.618 (95% CI: 0.481-0.754), and 0.786 (95% CI: 0.683-0.888), respectively. Moreover, statin users exhibited reduced MPO-DNA levels (0.174 vs. 0.218; P = 0.007), though VTE incidence differences (13.8% vs. 19.3%) lacked statistical significance.Serum MPO-DNA serves as a sensitive biomarker for VTE prediction in ICH, highlighting NETs as potential therapeutic targets. Statins could attenuate NETosis, but larger trials are required to validate their clinical efficacy and safety in VTE prevention for ICH patients.

Although direct oral anticoagulants (DOACs) have become a primary treatment choice for cancer-associated venous thromboembolism (CT), the safety and effectiveness of switching from low-molecular-weight heparin (LMWH) to DOACs in current users remains unclear.To evaluate the safety and effectiveness of switching to DOACs in patients with CT currently receiving LMWH therapy, a territory-wide cohort study using linked claims and registry databases in Taiwan was conducted. Between 2013 and 2021, patients with CT were identified and categorized as switchers to DOACs versus persistent LMWH users. Cox regression and Fine-Gray models with inverse probability of treatment weighting were used to estimate hazard ratios (HRs) for recurrent venous thromboembolism (VTE), major bleeding, and all-cause mortality.A total of 3,885 patients with LMWH-treated CT were included, with 2,103 (54.1%) being women and a mean age of 65.6 years at CT diagnosis, of which 2,373 (59.5%) switched to DOAC therapy. Compared with the persistent use of LMWH, switching to DOACs within 6 months was associated with no significant difference in recurrent VTE (HR: 0.86 [95% CI 0.50-1.49]) and major bleeding (HR: 0.89 [95% CI 0.67-1.18]), with a significantly lower risk of all-cause mortality (HR: 0.67 [95% CI 0.52-0.86]).Switching to DOACs is a safe and effective alternative to continuous LMWH in patients with CT. This recommendation applies regardless of the duration of initial LMWH therapy, overall treatment duration, and across various vulnerable patient groups.

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.