Thrombosis and haemostasis最新文献

Rapidly sorting patients with large vessel occlusion (LVO) ischemic stroke is crucial to ensure efficient transfers to stroke units. Peripheral monocyte subsets (classical Mon1, intermediate Mon2, non-classical Mon3) could be interesting candidate biomarkers in this setting: their profiles in the first hours after stroke symptom onset are unknown.To characterize monocyte subsets in patients admitted to emergency units for acute stroke suspicion.BOOST ("Biomarkers-algOrithm-for-strOke-diagnoSis-and-Treatment-resistance-prediction," NCT04726839) is a prospective multicenter cohort. Adult patients with symptoms suggesting acute stroke within the last 24 hours were included. Blood was collected upon admission before brain imaging. Flow cytometry (FCM) was performed on fresh blood with gating based on CD45/CD14/CD16/CD91 as well as on activation markers (CD62L/CD11b/CD86/HLA-DR/CCR2/ICAM-1/CX3CR1/TF).Of the 298 consecutive patients tested, mean age 64.0 ± 18.7 years, 64 (21.5%) had LVO stroke versus 234 (78.5%) other diagnosis (non-LVO ischemic stroke, cerebral venous thrombosis, intracranial hemorrhage, transient ischemic attack, and stroke mimics). The median time from symptom onset to sampling was 2.3 hours. We found a significantly lower proportion of Mon3 (geometric mean: -47%, p = 0.0093) and a higher proportion of Mon1 (+1.6%, p = 0.0296), suggesting earlier Mon1 mobilization and patrolling Mon3 consumption in LVO patients versus those without. Using linear-mixed-effect model, significant differences in ICAM-1 and HLA-DR expression on monocyte subsets were evidenced between LVO and other patients.This is the first study to evidence monocyte subset differences in LVO versus non-LVO patients at the time of admission, indicating an acute systemic response in LVO. Whether Mon assessment would add value for LVO diagnosis remains to be determined.

Tranexamic acid (TXA) reduces mortality in patients with trauma; however, optimal patient selection remains unclear. This study aimed to identify trauma subgroups most likely to benefit from TXA administration by integrating systematic evidence mapping with trauma phenotype analysis derived from the Japan Trauma Data Bank.We conducted a two-phase study: first, a systematic search of MEDLINE, Web of Science, and the Cochrane Library databases (inception to June 28, 2024) and identified randomized controlled trials (RCTs) evaluating TXA in trauma; second, we assessed TXA's association with mortality across phenotypes derived through machine learning-based clustering using 14 variables available during initial trauma care. Among eligible studies, control group mortality and number needed to treat (NNT) were calculated and visualized via bubble plots (size = sample size).Five RCTs (n = 894-20,127; published 2010-2023) and one phenotype study (n = 24,058; four phenotypes) were included, all reporting mortality as an outcome. At approximately 1 month post-injury, control group mortality in RCTs ranged from 10 to 21.8%, whereas in-hospital mortality across phenotypes ranged from 3.9 to 51.4%. NNT varied from 22 to 68 (RCTs) and from 10 to 98 (phenotype study), with an inverse relationship between baseline mortality and NNT, indicating greater TXA benefit in higher-risk groups.This study suggests that TXA is more effective in trauma subgroups with higher baseline mortality. Phenotype-driven stratification using initial clinical data may support more targeted TXA administration and improve patient outcomes. Further research is needed to validate these phenotypes for clinical implementation.

Epidemiological and experimental studies suggest cocoa flavanols and multivitamin-multimineral (MVM) supplements may confer arterial vascular benefits. However, their effects on clinical venous thromboembolic events have been infrequently examined.To evaluate whether cocoa extract (CE) or MVM supplementation reduces the risk of venous thromboembolism (VTE) among older adults.We conducted an ancillary study analysis of the COcoa Supplement and Multivitamin Outcomes Study (COSMOS), a completed randomized, double-blind, placebo-controlled, 2-by-2 factorial trial of CE and MVM supplementation for the prevention of cardiovascular disease and cancer among 21,442 older US adults. Our primary outcome was self-reported incident VTE, defined as the first reported deep vein thrombosis (DVT) or pulmonary embolism (PE) event after randomization; secondary outcomes were the individual components.Over a median follow-up of 3.5 years, 379 participants reported an incident VTE event (including 277 DVT and 165 PE). In intention-to-treat analyses, neither CE (HR: 0.88; 95% CI: 0.72, 1.08) nor MVM (HR: 0.89; 95% CI: 0.73, 1.09) significantly reduced VTE risk, with similar findings for DVT and PE. Exploratory latency and per-protocol analyses suggested potential patterns of benefit that merit further evaluation.In this large trial of older adults, neither CE nor MVM supplementation significantly reduced the risk of VTE or its component parts in intention-to-treat analyses. Additional research may help clarify whether these supplements influence VTE risk in other contexts or populations.

Weak hand grip strength (HGS) and obesity separately increase the risk of venous thromboembolism (VTE). Whether the combination of these risk factors yields excess VTE risk is unclear. We aimed to investigate the joint effect of HGS and obesity on the risk of VTE in a population-based cohort.A total of 13,616 participants from the Tromsø study (enrolled: 1994-2016) were included, and incident VTEs were recorded throughout 2020. HGS was categorized into weak (≤25th percentile) and normal (>25th percentile). Obesity was defined as a body mass index ≥ 30 kg/m². Cox regression was applied to estimate hazard ratios (HRs) with 95% confidence intervals (CI) according to combined categories of HGS and obesity adjusted for age, sex, height, cardiovascular disease, cancer, and physical activity. Relative excess risk due to interaction (RERI) and attributable proportion (AP) were calculated with 95% CI.The combination of weak HGS and obesity yielded an additive 1.8-fold increased risk of overall VTE (95% CI: 1.25-2.55) compared with nonobese individuals with normal HGS. The corresponding HR was 1.23 (95% CI: 0.97-1.56) in nonobese with weak HGS, and 1.47 (95% CI: 1.14-1.90) in obese with normal HGS. In subgroup analyses of unprovoked VTE, risk estimates were supra-additive in those obese with weak HGS (HR: 2.68, (95% CI: 1.64-4.37), RERI 1.63 (95% CI: 0.36-2.91), AP 0.61 (95% CI: 0.34-0.88)), supporting biological interaction between the exposures.The joint effect of weak HGS and obesity was additive for overall VTE, and supra-additive for unprovoked VTE, where 61% of the unprovoked VTEs in the combined category could be attributed to the interaction between HGS and obesity.

Emicizumab is a bispecific monoclonal antibody that mimics the cofactor function of activated factor (F) VIIIa, facilitating the FIXa-catalyzed activation of FX. Emicizumab binds to FIX/IXa and FX with considerably lower affinity than FVIIIa, suggesting that FVIII may outcompete emicizumab when present at higher concentrations. However, the interaction between emicizumab and FVIII at low FVIII concentrations is not well characterized. The current study aimed to assess the pharmacodynamic interaction between emicizumab and FVIII using classical pharmacological concepts of additivity and synergy.Thrombin generation was used as a surrogate marker of hemostatic capacity, providing well-defined quantitative outcome parameters. Tissue factor-triggered thrombin generation was measured in FVIII-deficient plasma supplemented with variable concentrations of emicizumab and recombinant FVIII, alone or in combination.A synergistic interaction between emicizumab and FVIII was observed, resulting in enhanced endogenous thrombin potential and peak thrombin generation beyond the levels expected from either agent alone. This synergistic effect was evident at low FVIII concentrations and was no longer observed once FVIII levels exceeded 20 IU/dl.These findings may provide a pharmacodynamic explanation for the pronounced hemostatic effect of emicizumab at low FVIII levels and offer a conceptual framework for evaluating synergistic interactions between novel non-factor therapies and intrinsic FVIII.

Disseminated intravascular coagulation (DIC) is a serious condition characterized by systemic coagulation activation leading to thrombotic and hemorrhagic complications. Although the characteristics of DIC vary depending on the underlying cause, studies directly comparing coagulation/fibrinolysis laboratory findings across a wide range of underlying diseases are limited.We investigated the characteristics of coagulation/fibrinolysis laboratory results, the frequency of DIC, and the impact of DIC on patient prognosis across various underlying diseases in a critical care setting.This was a single-center retrospective observational study of 1,665 critically ill patients admitted between January 1, 2010, and December 21, 2022. Patients were categorized based on underlying diseases, which included out-of-hospital cardiac arrest, sepsis, trauma, burn, and heat stroke. We retrospectively collected data on background, DIC scores, laboratory results, and in-hospital mortality rates of patients.Significant heterogeneity in coagulation/fibrinolysis laboratory findings was observed, with all findings differing based on the underlying disease (p < 0.001). For example, patients with trauma-associated DIC showed significantly elevated D-dimer and fibrin/fibrinogen degradation product levels, while those with burn-associated DIC tended to have high platelet counts and a rapid decrease in antithrombin activity following admission. Among all underlying diseases, the development of DIC was associated with an increase in in-hospital mortality. This association was particularly strong in patients with trauma or burns.The coagulation/fibrinolysis laboratory findings, along with the clinical trajectory of DIC, exhibit remarkable heterogeneity depending on the precipitating cause. Development of DIC in patients with burn or trauma is strongly associated with increased in-hospital mortality.

Edoxaban is a novel oral anticoagulant that directly inhibits factor Xa. The ENGAGE population pharmacokinetic (PopPK) model was established using data from the ENGAGE AF-TIMI 48 trial, which included over 21,000 participants, predominantly (81%) White/Caucasian individuals. However, its applicability to Chinese patients necessitates further evaluation. This study assessed the suitability of the ENGAGE PopPK model for Chinese patients with nonvalvular atrial fibrillation (NVAF).We analyzed 730 pharmacokinetic (PK) plasma samples from 104 Chinese NVAF patients using nonlinear mixed-effects modeling.A two-compartment model with first-order absorption and linear elimination optimally described the PK data of edoxaban in this cohort. Body weight (WT) and creatinine clearance were identified as significant covariates of apparent clearance (CL/F), and positively correlated with CL/F. Model-based simulations demonstrated that, in the 30 mg once-daily (q.d.) dosing group, patients with moderate renal impairment and low WT experienced higher systemic exposure than those with only one of these attributes. Additionally, patients with moderate renal impairment, whether alone or combined with low WT, displayed elevated steady-state trough concentrations (C_min,ss) compared to those receiving the 60 mg q.d. dose.Our PopPK model characterizes the PK profile of edoxaban in Chinese NVAF patients, identifies critical covariates influencing drug exposure, and proposes an evidence-based dosing regimen tailored to this population. This trial was registered at www.clinicaltrials.gov as #NCT05320627.

Despite restored patency, catheter-directed thrombolysis (CDT) has variable efficacy in preventing post-thrombotic syndrome (PTS); biomarkers may clarify PTS pathophysiology and guide patient selection for CDT.To investigate relationships between biomarkers, patency, popliteal reflux, and PTS.This prespecified CAVA trial subanalysis included patients with first acute iliofemoral deep vein thrombosis (DVT), randomized to standard treatment (ST) or ultrasound accelerated CDT (UACDT). Baseline blood samples were analyzed for fibrinogen, CRP, IL-6, IL-10, VEGF-A, P-selectin, E-selectin, ICAM-1, VCAM-1, MMP-2, MMP-9, and adiponectin. Patency and reflux (duplex ultrasound), and PTS (Villalta score) were assessed at 1-year and long-term follow-up (LT).Among 108 patients (51 UACDT, 57 ST), absence of patency at 1-year was associated with higher baseline CRP and fibrinogen in both groups, and elevated IL-6 and VEGF-A in the ST group. Reflux at LT was associated with lower IL-6 and adiponectin in the UACDT group. (Moderate-to-severe) PTS at LT was associated with higher baseline MMP-2 and lower IL-10 in the UACDT group, and lower baseline VCAM-1 and adiponectin in the ST group.Pro-inflammatory processes are linked to reduced patency, with UACDT improving patency in patients with enhanced inflammatory responses. LT reflux is associated with impaired vasoprotective properties. PTS involves impaired anti-inflammatory responses and tissue remodelling both not modifiable by UACDT. Therefore, biomarker-guided treatment selection may potentially improve treatment outcome.

Rule-based natural language processing (NLP) tools can identify pulmonary embolism (PE) via radiology reports. However, their external validity remains uncertain.In this cross-sectional study, 1,712 hospitalized patients (with and without PE) at Mass General Brigham (MGB) hospitals (2016-2021) were analyzed. Two previously published NLP algorithms were applied to radiology reports to identify PE. Chart review by two physicians was the reference standard. We tested three approaches: (A) NLP applied to all patients; (B) NLP limited to radiology reports of patients with principal or secondary International Classification of Diseases 10th revision (ICD-10) PE discharge codes; and (C) NLP applied to patients with PE discharge codes or a Present-on-Admission (POA) indicator ("Y") for PE. All others were assumed PE-negative in Approaches B and C to minimize NLP false positives. Weighted estimates were derived from the MGB hospitalized cohort (n = 381,642) to calculate F1 scores (as the harmonic mean of sensitivity and positive predictive value [PPV]).In Approach A, both NLP tools showed high sensitivity (82.5%, 93.0%) and specificity (98.9%, 98.7%) but low PPV (60.3%, 59.6%). Approach B improved PPV (95.2%, 94.9%) but reduced sensitivity (74.1%, 76.2%), while Approach C preserved both high sensitivity (82.5%, 93.0%) and PPV (95.6%, 95.8%). Approach C demonstrated the best performance, yielding significantly higher F1 scores for both NLP tools (88.6%, 94.4%) compared with Approach A (69.7%, 72.6%) and Approach B (83.3%, 84.5%) (P < 0.001).The accuracy of PE detection improves when rule-based NLP algorithms are operationalized using administrative claims data in addition to radiology reports.

Thrombosis drives substantial global mortality across atrial fibrillation, venous thromboembolism, and atherosclerosis. However, clinical scores treat risk as a static variable and omit evolving comorbidities, functional biomarkers, anatomy, and treatment exposure, leading to misclassification and preventable events. This statement advances a unified scientific agenda for patient-specific digital twins that dynamically integrate multimodal longitudinal data with mechanistic insight to predict thrombogenesis risks. We position these digital twins as hybrid models anchored in physics and data-driven algorithms that can simulate disease progression and therapy. The goal of this approach is to refine stroke and bleeding estimation beyond current clinical rules. Continuous updating from imaging data, laboratory test results, wearables, and electronic health records supports dynamic risk trajectories and adaptive care pathways, facilitating continuous risk reassessment. This statement analyzes gaps in data quality, calibration, validation, and uncertainty quantification that presently limit the clinical translation of this technology. Research priorities are then proposed for multiscale thrombosis modelling, physics-informed learning, probabilistic forecasting, and regulatory-compliant data stewardship. Finally, we outline translation to in silico trials, regulatory alignment, and hospital workflows that link predictions to decisions. By articulating shared challenges across thrombosis-driven diseases and reframing risk as a time-varying measurable quantity, this statement lays a foundation for developing digital twin approaches that support a shift from population heuristics towards precise, timely thrombosis care. These advances are essential for translating digital twin technology from research to clinical practice, enabling dynamic risk prediction and personalized anticoagulation therapy.