Seminars in thrombosis and hemostasis最新文献

Hemophilia A and hemophilia B are rare genetic disorders characterized by low plasma levels of coagulation factor VIII or factor IX, resulting in a bleeding tendency with a clinical severity proportional to the degree of the clotting factor deficiency. Although rare, hemophilia patients can paradoxically experience thrombotic events that complicate the clinical picture and the management by physicians operating at hemophilia treatment centers. Such thromboembolic complications, which can involve either the arterial or the venous districts, recognize various causes, including aging (due to the progress of care during the last three decades) and inherited and acquired (treatment-related) risk factors. These determinants often interact with each other to increase patients' susceptibility to thrombosis. In this narrative review, we summarize the current knowledge on the mechanisms, clinical presentation, and management of thrombotic complications in hemophilia patients.

Venous thromboembolism (VTE), including deep vein thrombosis (DVT), and pulmonary embolism (PE), is a common complication in patients with ischemic stroke. Several prophylactic strategies are used to reduce the risk of VTE. However, there is still a lack of consensus on the optimal strategy due to the lack of randomized controlled trials (RCTs) directly comparing different interventions. The objective of this study was to explore the efficacy and safety of different thromboembolic prophylaxis strategies in patients with ischemic stroke. We conducted a systematic literature review to identify all eligible RCTs, searching MEDLINE and Embase up to December 31, 2024. We considered DVT and PE as efficacy outcomes and intracranial and extracranial hemorrhage as safety outcome measures. Relevant data were extracted for network meta-analyses. A random-effects model was used for the analysis. A total of 33 RCTs were included in the analysis. Network meta-analysis revealed that low-molecular-weight heparin (LMWH) and heparinoid were associated with significantly decreased risk of DVT and PE compared with no prophylaxis, with risk ratios of 0.18 (95% confidence interval: 0.10-0.32) and 0.36 (0.20-0.63), respectively. However, LMWH and heparinoid were associated with an increased risk of extracranial hemorrhage compared with no prophylaxis, with a risk ratio of 2.03 (1.24-3.34). Our study supports the use of LMWH and heparinoid as the primary thromboembolic prophylaxis measure in patients with acute ischemic stroke. Further, high-quality RCTs are needed to strengthen the evidence base and determine the optimal prophylactic strategy in these patients.

Red light therapy is emerging as a potential non-pharmacological modulator of thrombosis and hemostasis. Photobiomodulation with red, near-infrared (NIR), and far-infrared (FIR) wavelengths has been shown to influence nitric oxide release, endothelial function, platelet activation, and vascular tone. These effects align with the components of Virchow's triad (i.e., endothelial dysfunction, stasis, and hypercoagulability), and ameliorate thromboinflammation. Experimental data indicate that photobiomodulation may be effective to reduce platelet aggregation, von Willebrand factor activity, and improve microvascular perfusion. However, controversy remains regarding whether observed benefits reflect active red/NIR effects or simply the exclusion of pro-thrombotic blue light. Limitations in tissue penetration, protocol standardization, and translational modeling pose challenges for clinical implementation. Despite these uncertainties, red light therapy offers promise in high-risk patients where conventional anticoagulation is limited by bleeding risk. Future studies must define optimal dosing parameters, clarify mechanistic pathways, and evaluate efficacy in randomized clinical trials to establish its role in contemporary thrombosis management.

Venous thromboembolism (VTE) remains a leading cause of cardiovascular morbidity and mortality, despite advances in imaging and anticoagulation. VTE arises from diverse and overlapping risk factors, such as inherited thrombophilia, immobility, malignancy, surgery or trauma, pregnancy, hormonal therapy, obesity, chronic medical conditions (e.g., heart failure, inflammatory disease), and advancing age. Clinicians, therefore, face challenges in balancing the benefits of thromboprophylaxis against the bleeding risk. Existing clinical risk scores often exhibit only modest discrimination and calibration across heterogeneous patient populations. Machine learning (ML) has emerged as a promising tool to address these limitations. In imaging, convolutional neural networks and hybrid algorithms can detect VTE on CT pulmonary angiography with areas under the curves (AUCs) of 0.85 to 0.96. In surgical cohorts, gradient-boosting models outperform traditional risk scores, achieving AUCs between 0.70 and 0.80 in predicting postoperative VTE. In cancer-associated venous thrombosis, advanced ML models demonstrate AUCs between 0.68 and 0.82. However, concerns about bias and external validation persist. Bleeding risk prediction models remain challenging in extended anticoagulation settings, often matching conventional models. Predicting recurrent VTE using neural networks showed AUCs of 0.93 to 0.99 in initial studies. However, these lack transparency and prospective validation. Most ML models suffer from limited external validation, "black box" algorithms, and integration hurdles within clinical workflows. Future efforts should focus on standardized reporting (e.g., Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis [TRIPOD]-ML), transparent model interpretation, prospective impact assessments, and seamless incorporation into electronic health records to realize the full potential of ML in VTE.

Acute ischemic stroke leads to rapid and progressive neuronal losses. Early revascularization with thrombolytics and/or endovascular thrombectomy plays an important role in salvaging brain infarction. Currently, alteplase and tenecteplase are approved thrombolytics for the treatment of acute ischemic stroke, whereas favorable outcomes of reteplase have recently been reported in a phase 3 clinical trial. These thrombolytics share common and distinct pharmacological characteristics, which contribute to their efficacy and safety in patients. In this review, biological profiles of alteplase, tenecteplase, and reteplase, including their advantages versus disadvantages in acute ischemic stroke, are discussed. Tenecteplase has high fibrin specificity, increased resistance to plasminogen activator inhibitor-1 (PAI-1), wider concentration-response curve, and less off-target activities, which support its efficacy with low incidence of symptomatic intracranial hemorrhage (sICH). Reteplase greatly penetrates into the clot with prolonged retention, generating durable clot lysis. This activity might be associated with its excellent clinical outcomes in patients, although reteplase is sensitive to PAI-1. Notably, reteplase and alteplase produce off-target activities by inducing hypofibrinogenemia and hypoplasminogenemia, which may increase risk of hemorrhagic transformation. Moreover, orolingual angioedema is a life-threatening complication of all thrombolytics. Mechanistically, an increase in plasmin by thrombolytics leads to bradykinin generation. In addition, plasmin activates mast cell degranulation (e.g., histamine release). Together, these biopharmacological data of thrombolytics promote insights into their clinical outcomes, and might provide comprehensive bases for future research.

Although several studies have investigated the roles of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and monocyte-to-high-density lipoprotein (HDL) cholesterol ratio (MHR), the findings remain inconclusive and warrant further investigation, particularly regarding their utility in predicting in situ inferior vena cava thrombosis (iIVCT). This study aimed to explore the relationship between composite inflammatory ratios (CIRs) measured within 24 hours after inferior vena cava filter (IVCF) placement and the development of iIVCT, as well as to evaluate their predictive value. A retrospective case-control study was conducted on 154 patients with proximal deep vein thrombosis (DVT) who underwent IVCF implantation between April 2016 and June 2023. Among them, 50 developed iIVCT, while 104 did not. Compared with the non-iIVCT group, patients who developed iIVCT had significantly higher PLR, NLR, LMR, and MHR levels. Multivariate regression analysis showed that NLR, PLR, LMR, and MHR were independently associated with iIVCT, with adjusted hazard ratios of 1.25, 1.16, and 3.32, respectively. Receiver operating characteristic analysis demonstrated that NLR had the highest area under the curve (area under the curve = 0.79), significantly outperforming PLR, LMR, and MHR in predictive accuracy (all p < 0.05, DeLong's test). These findings suggest that CIRs are useful and easily accessible biomarkers for identifying patients at risk of iIVCT following IVCF placement. Notably, NLR emerged as the most effective marker, showing superior discriminatory power compared with the other indicators.

Venous thromboembolism is often underestimated in transfusion-dependent thalassemia (TDT) patients, as arterial thrombotic events are more commonly observed. Although therapeutic advancements have transformed this disease from a once-fatal childhood disease into a manageable chronic condition, some treatments may contribute to an increased risk of thrombosis. Additionally, the prolonged life expectancy of these patients further contributes to the overall thrombotic risk. Patients with thalassemia major present multiple challenges when considering anticoagulation therapy. The decision-making process is complicated by a delicate balance between thrombotic risk-driven by disease-related and treatment-associated factors-and potential bleeding tendencies, particularly in the presence of comorbid conditions such as liver dysfunction, hypersplenism, or thrombocytopenia. Therefore, ongoing assessment of both thrombotic and bleeding risk and the implementation of appropriate preventive strategies are essential to optimize patient outcomes. This document presents a consensus statement from the Steering Committee of the Hemostasis Working Group of the Hellenic Society of Hematology, offering guidance on thromboprophylaxis and anticoagulation management in adult TDT patients.

Arterial and venous thromboembolism represent major contributors to global morbidity and mortality. Despite substantial progress in risk stratification and clinical management, a significant proportion of thromboembolic events occur in individuals not classified within traditional high-risk groups indicating the involvement of additional, non-conventional risk factors in thrombotic pathophysiology.Recent evidence has highlighted the gut microbiome as a critical determinant of human health, with increasing recognition of its role in cardiovascular and thrombotic disorders. Furthermore, the gut microbiome constitutes a modifiable risk factor, offering new horizons for therapeutic intervention and emerging evidence suggests that alterations in the microbiome may significantly impact thrombotic risk.Moreover, microbiome-derived metabolites have gathered considerable scientific attention for their potential involvement in the initiation and progression of thrombosis. These metabolites may serve as novel biomarkers, complementing conventional risk indicators in disease diagnosis, prognosis, screening, and patient monitoring. Microbiome-derived metabolites may hold dual utility, first as diagnostic and prognostic biomarkers, and, second, as potential targets for pharmacologic modulation. Collectively, these findings underscore the growing significance of the gut microbiome as an environmental factor in thromboembolic disease and justify the constantly increasing employment of the scientific community in several aspects of health and disease.

Central venous catheter (CVC) dysfunction is a common complication of indwelling CVCs for hospitalized children, often secondary to intraluminal thrombosis. We sought to characterize thrombolytic agent use for restoration of CVC patency and assess its association with hospital-acquired venous thromboembolism (HA-VTE). We performed a multicenter retrospective cohort study using the Pediatric Health Information Systems database, including critically ill children < 18 years of age with a CVC in 2023 at 44 participating centers. Exclusion criteria were VTE present on admission and thrombolytic agent (i.e., alteplase or urokinase) use for systemic or catheter-directed thrombolysis or adhesiolysis. The primary outcome was HA-VTE frequency, including deep venous thrombosis and pulmonary embolism, compared by cohorts with or without exposure to thrombolytic agents. In addition to comparative analyses, adjusted logistic regression was employed to assess the association between thrombolytic agent exposure and HA-VTE. Of 9,822 children, including 10,904 CVCs, the median participating center prescribing rate of thrombolytic agents was 33.8% (interquartile range, IQR: 25-43.5%), and the median HA-VTE rate was 11.9% (IQR: 9.2-15.8%). VTE events exhibited a bimodal age distribution (i.e., greatest among infants and adolescents) without variation by CVC type. In a multivariable conditional logistic model accounting for prothrombotic risk factors, severity of illness markers, and hospital center, thrombolytic agent use for CVC dysfunction was independently associated with HA-VTE (adjusted odds: 1.89; 95% confidence interval: 1.64-2.19, p < 0.001). Among critically ill children, thrombolytic agent use for CVC dysfunction was common and independently associated with HA-VTE.