Thrombosis research最新文献

英文中文

The fibrinolytic system in disease: From molecular pathways to clinical outcomes 疾病中的纤溶系统：从分子途径到临床结果。

IF 3.4 3区医学 Q1 HEMATOLOGY

Thrombosis research

Pub Date : 2025-10-13 DOI: 10.1016/j.thromres.2025.109504

Mohamed Nazem Alibrahim , Khaled A. Sahli , Fahad S. Alshehri

The fibrinolytic system, essential in maintaining hemostatic balance, tightly regulates blood clot dissolution through a complex interplay of activators (e.g., t-PA, u-PA), inhibitors (e.g., PAI-1, α2-antiplasmin), and modulators such as thrombin-activatable fibrinolysis inhibitor (TAFI). Dysregulation of fibrinolysis contributes significantly to various pathological states. In liver diseases, alterations in fibrinolytic proteins, including elevated tissue plasminogen activator (t-PA) and reduced plasminogen activator inhibitor-1 (PAI-1), predispose patients variably toward bleeding or thrombosis, with clinical implications for management in liver transplantation and cirrhosis. In cardiovascular disease, impaired fibrinolysis, characterized by increased clot density and elevated PAI-1, associates with heightened risks of myocardial infarction, stroke, and peripheral arterial disease, driving current therapeutic strategies toward enhancing fibrinolytic potential. Sepsis frequently induces fibrinolytic shutdown, driven by elevated PAI-1 and TAFI, exacerbating microthrombosis, disseminated intravascular coagulation (DIC), and organ dysfunction, emerging therapeutic targets include PAI-1 modulation. In trauma, fibrinolytic dysregulation manifests as either hyperfibrinolysis, primarily induced by shock-associated elevations in t-PA, or fibrinolysis shutdown, often following severe tissue injury, each demanding distinct therapeutic approaches such as timely antifibrinolytic administration (tranexamic acid) or experimental profibrinolytic treatments. This review highlights critical insights into fibrinolytic mechanisms across these clinical conditions, advocating further research toward refining diagnostics, personalized interventions, and targeted modulation of the fibrinolytic system to optimize clinical outcomes.

纤溶系统是维持止血平衡所必需的，它通过激活剂（如t-PA、u-PA）、抑制剂（如PAI-1、α - 2抗纤溶酶）和调节剂（如凝血酶活化纤维蛋白溶解抑制剂（TAFI））的复杂相互作用，严格调节血凝块溶解。纤维蛋白溶解失调对各种病理状态有重要影响。在肝脏疾病中，纤溶蛋白的改变，包括组织型纤溶酶原激活物（t-PA）升高和纤溶酶原激活物抑制剂-1 （PAI-1）降低，使患者易发生出血或血栓形成，对肝移植和肝硬化的治疗具有临床意义。在心血管疾病中，以血栓密度增加和PAI-1升高为特征的纤维蛋白溶解受损与心肌梗死、中风和外周动脉疾病的风险增加有关，这促使当前的治疗策略朝着增强纤维蛋白溶解潜能的方向发展。脓毒症经常引起纤维蛋白溶解关闭，由PAI-1和TAFI升高驱动，加剧微血栓形成，弥散性血管内凝血（DIC）和器官功能障碍，新的治疗靶点包括PAI-1调节。在创伤中，纤溶异常表现为高纤溶，主要是由休克相关的t-PA升高引起的，或纤溶关闭，通常是在严重的组织损伤之后，每种都需要不同的治疗方法，如及时的抗纤溶药物（氨甲环酸）或实验性纤溶治疗。这篇综述强调了在这些临床条件下纤维蛋白溶解机制的关键见解，提倡进一步研究细化诊断、个性化干预和纤维蛋白溶解系统的靶向调节，以优化临床结果。

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引用次数: 0

The role of platelets in the regulation of myeloid-derived suppressor cells in immune thrombocytopenia 血小板在免疫血小板减少症中调节髓源性抑制细胞的作用

IF 3.4 3区医学 Q1 HEMATOLOGY

Thrombosis research

Pub Date : 2025-10-13 DOI: 10.1016/j.thromres.2025.109506

Mohammad Reza Moghaddasnejad , Negar Sadat Sherafat , Najmaldin Saki

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immune regulatory cells that play crucial roles in suppressing immune responses and promoting immune tolerance in autoimmune diseases. Platelets, historically recognized for their role in hemostasis, have recently attracted significant attention for their immune regulatory functions, mainly through their interactions with immune cells, including MDSCs. In patients with immune thrombocytopenia (ITP), both the quantity and suppressive function of MDSCs are decreased. However, following treatment and subsequent elevation of platelet counts, the mean level and suppressive capacity of MDSCs increase. Studies have indicated that platelet-derived products can increase the suppressive capacity of MDSCs in ITP, thereby promoting immune tolerance and reducing inflammation. Conversely, specific platelet-secreted molecules such as TGF-β and histamine play complex roles and are capable of both augmenting and inhibiting MDSC activity, depending on the context. Understanding these interactions reveals potential targets in platelet-MDSC signaling pathways as novel approaches for ITP management. Future research could investigate targeted therapies that modulate MDSC function by enhancing or inhibiting specific platelet-derived mediators, leading to the development of innovative treatments for autoimmune diseases such as ITP.

髓源性抑制细胞（Myeloid-derived suppressor cells, MDSCs）是一种异质的免疫调节细胞群，在自身免疫性疾病中抑制免疫应答和促进免疫耐受起着至关重要的作用。血小板历来被认为具有止血作用，最近由于其免疫调节功能（主要通过其与免疫细胞（包括MDSCs）的相互作用）而引起了人们的极大关注。在免疫性血小板减少症（ITP）患者中，MDSCs的数量和抑制功能都下降。然而，在治疗和随后的血小板计数升高后，MDSCs的平均水平和抑制能力增加。研究表明，血小板衍生产品可以增加MDSCs对ITP的抑制能力，从而促进免疫耐受和减少炎症。相反，特定的血小板分泌分子，如TGF-β和组胺发挥复杂的作用，能够增强和抑制MDSC活性，这取决于环境。了解这些相互作用揭示了血小板- mdsc信号通路的潜在靶点，作为ITP管理的新方法。未来的研究可能会探索通过增强或抑制特异性血小板衍生介质来调节MDSC功能的靶向治疗，从而开发出治疗自身免疫性疾病（如ITP）的创新疗法。

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引用次数: 0

Systematic review of a machine learning model for prediction of venous thromboembolism risk 用于预测静脉血栓栓塞风险的机器学习模型的系统综述

IF 3.4 3区医学 Q1 HEMATOLOGY

Thrombosis research

Pub Date : 2025-10-11 DOI: 10.1016/j.thromres.2025.109507

Wen-jing Ge , Teng-fei Zhu , Wen-jie Ge , Xin-yi Zhu , Ai-qin Chu

Objective

This systematic review aims to evaluate the methodological quality, performance, and clinical applicability of machine learning (ML) models for predicting the risk of venous thromboembolism (VTE) in hospitalized patients. Specifically, we aim to assess the methodological quality and reporting transparency of the included studies, with a focus on their risk of bias and adherence to reporting guidelines.

Methods

A systematic review by use of the databases Cochrane Library, Web of Science, Embase, PubMed, CNKI, VIP Journal Database, Wanfang Database, and the Chinese Biomedical Literature Database. The study was registered at PROSPERO before data collection and PRISMA guidelines were followed. The search was conducted to identify all relevant studies published from the inception of database up to August 1, 2024. Two independent researchers screened the literature and extracted data. Model quality was assessed using the PROBAST appraisal tool and a modified TRIPOD+AI framework, alongside reported model performance metrics.

Results

A total of seventeen studies were included, comprising 65 VTE ML models with sample sizes ranging from 120 to 9213. All models demonstrated an area under the curve (AUC) >0.7. Twenty-three ML algorithms were employed, with logistic regression (LR) being the most frequently used (n = 11), followed by XGBoost (n = 10) and random forests (RF) (n = 9). Thirteen studies utilized various stochastic algorithms. Most studies used Bootstrap or 10-fold cross-validation for internal validation, but lacked external validation, leading to a high overall risk of bias. Key predictors in these models included D-dimer, history of thrombosis, history of hypertension, age, and complications.

Conclusions

Existing evidence suggests that ML models can effectively predict VTE outcomes. However, most models suffer from poor methodological quality, lack of external validation, and limited generalizability. Future research should focus on large-scale, multi-center prospective studies that are based on clinical practice, improve external validation, and develop optimized local VTE risk assessment and decision support tools for better integration into clinical practice.

目的本系统综述旨在评估机器学习（ML）模型在预测住院患者静脉血栓栓塞（VTE）风险方面的方法学质量、性能和临床适用性。具体而言，我们旨在评估纳入研究的方法学质量和报告透明度，重点关注其偏倚风险和对报告指南的遵守情况。方法采用Cochrane Library、Web of Science、Embase、PubMed、CNKI、VIP期刊库、万方数据库、中国生物医学文献数据库进行系统综述。在数据收集和PRISMA指南遵循之前，该研究在PROSPERO注册。检索自数据库建立至2024年8月1日发表的所有相关研究。两位独立研究人员筛选文献并提取数据。使用PROBAST评估工具和改进的TRIPOD+AI框架评估模型质量，同时报告模型性能指标。结果共纳入17项研究，包括65个VTE ML模型，样本量为120 ~ 9213。所有模型的曲线下面积（AUC）均为0.7。采用了23种ML算法，其中最常用的是逻辑回归（LR）（n = 11），其次是XGBoost （n = 10）和随机森林（RF）（n = 9）。13项研究使用了各种随机算法。大多数研究使用Bootstrap或10倍交叉验证进行内部验证，但缺乏外部验证，导致总体偏倚风险高。这些模型的关键预测因素包括d -二聚体、血栓形成史、高血压史、年龄和并发症。结论已有证据表明ML模型能有效预测静脉血栓栓塞的预后。然而，大多数模型都存在方法质量差、缺乏外部验证和有限的可推广性的问题。未来的研究应注重基于临床实践的大规模、多中心前瞻性研究，完善外部验证，开发优化的局部静脉血栓栓塞风险评估和决策支持工具，更好地融入临床实践。

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引用次数: 0

Has systemic thrombolysis run its course? A systematic review and network meta-analysis of patients with intermediate- and high-risk pulmonary embolism 全身性溶栓已经结束了吗？中高危肺栓塞患者的系统回顾和网络荟萃分析

IF 3.4 3区医学 Q1 HEMATOLOGY

Thrombosis research

Pub Date : 2025-10-09 DOI: 10.1016/j.thromres.2025.109503

Gal Aviel , Bruria Raccah-Hirsh , Rafat Abu-Ghannam , Noa Oren , David Planer , Gabby Elbaz-Greener , Eyal Herzog , Ori Wald , Amit Korach

Background

Traditionally, first-line reperfusion strategy recommendation for patients with hemodynamically significant pulmonary embolism (PE) is systemic thrombolysis (ST). ST is associated with serious adverse events. Surgical embolectomy (SE) and catheter-directed interventions (CDI) are reported to be safe, improve right ventricular (RV) function and survival.

Objectives

To compare the outcomes of patients with hemodynamically significant PE treated with CDI or SE to ST.

Methods

We systematically reviewed studies of patients with intermediate- or high-risk PE that received reperfusion therapy. The primary outcome was in-hospital mortality. Secondary outcomes included major bleeding and right ventricular function. We conducted a network meta-analysis and generated pooled survival curves using approximated individual-level time-to-event data.

Results

Of 4283 studies identified, 15 studies were included in the final analysis involving 1598 patients (CDI = 683 patients, SE = 224, ST = 691), encompassing 3595.5 patient years. A network meta-analysis revealed a significant decrease in early mortality in patients treated with CDI or SE compared to ST (odds-ratio (OR) 0.34, 95 %-confidence interval (CI) 0.17–0.0.68, and OR = 0.37, 95 % CI (0.16–9.85), respectively). Ranking the different therapeutic modalities, CDI had the highest P-score (0.87), followed by SE (0.63), and ST (0.0008). Compared to ST, CDI resulted in less RV dysfunction (OR = 0.28, 95 % CI (0.1–0.76) and a trend for less bleeding complications.

Conclusions

In this study, CDI and SE were associated with superior survival compared to ST in patients with moderate- and high-risk PE. CDI resulted in improved RV function.

Well-designed randomized controlled trials are needed to confirm these findings and inform future guideline recommendations.

传统上，对于血流动力学显著的肺栓塞（PE）患者，一线再灌注策略推荐是全身溶栓（ST）。ST与严重不良事件相关。据报道，外科栓塞切除术（SE）和导管定向干预（CDI）是安全的，可以改善右心室（RV）功能和生存率。目的比较血液动力学意义显著的PE患者接受CDI或SE与st治疗的结果。方法系统回顾了接受再灌注治疗的中高危PE患者的研究。主要终点是住院死亡率。次要结局包括大出血和右心室功能。我们进行了网络荟萃分析，并使用近似的个人水平事件时间数据生成了合并生存曲线。结果在纳入的4283项研究中，最终分析纳入15项研究，涉及1598例患者（CDI = 683例，SE = 224, ST = 691），涵盖3595.5患者年。网络荟萃分析显示，与ST相比，接受CDI或SE治疗的患者早期死亡率显著降低（优势比（or） 0.34, 95%可信区间（CI） 0.17-0.0.68, or = 0.37, 95% CI(0.16-9.85)）。不同治疗方式中，CDI的p值最高（0.87），SE次之（0.63），ST次之（0.0008）。与ST相比，CDI导致的RV功能障碍更少（OR = 0.28, 95% CI(0.1-0.76)），出血并发症也更少。结论：在本研究中，与ST相比，CDI和SE与中高危PE患者的生存率更高。CDI改善了右心室功能。需要精心设计的随机对照试验来证实这些发现，并为未来的指南建议提供信息。

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引用次数: 0

Predictors of pulmonary infarction in pediatric pulmonary embolism: A retrospective cohort study 儿童肺栓塞中肺梗死的预测因素：一项回顾性队列研究。

IF 3.4 3区医学 Q1 HEMATOLOGY

Thrombosis research

Pub Date : 2025-10-09 DOI: 10.1016/j.thromres.2025.109502

Shuxuan Li , Min Wang , Yongsheng Xu

Objective

Pulmonary infarction (PI) complicating pulmonary embolism (PE) is rarely reported in pediatric populations. This study aimed to identify risk factors associated with PI development and evaluate the diagnostic utility of predictive indicators.

Methods

This retrospective study enrolled patients aged <18 years diagnosed with PE by CTA. Data collected included demographics, medical histories, clinical manifestations, laboratory findings, and imaging results. Patients were assessed using simplified Wells score, simplified revised Geneva score, and Pulmonary Embolism Severity Index. Logistic regression and receiver operating characteristic curves were employed to evaluate risk factors and diagnostic efficacy.

Results

Among 41 pediatric patients diagnosed with PE (26 non-PI vs. 15 PI), 95 % (39/41) showed no signs or history of deep vein thrombosis. The three scoring systems performed poorly in predicting pediatric PE or PI. Features nominally associated with PI (p < 0.05 but q > 0.05) included pleural effusion, maximum temperature, lymphocyte ratio, chest pain, blood urea nitrogen (BUN), neutrophil ratio, maximum D-dimer, leukocyte count, and neutrophil count. Chest pain (aOR = 6.85, p < 0.05), BUN (aOR = 2.77, p = 0.04), and maximum temperature (aOR = 3.83, p = 0.03) were identified as independent risk factors for the occurrence of PI. The logistic regression model for predicting PI (AUC = 0.846) significantly outperformed the simplified Wells model (AUC = 0.640).

Conclusions

In situ pulmonary artery thrombosis represents the primary form of PE in pediatric patients. Chest pain, BUN, and maximum temperature were identified as independent risk factors for the occurrence of PI. The logistic regression model demonstrates excellent efficacy and may serve as a tool for the future development of a PI scoring system.

目的：肺梗死（PI）合并肺栓塞（PE）在儿科人群中很少报道。本研究旨在确定与PI发展相关的危险因素，并评估预测指标的诊断效用。结果：在41例诊断为PE的儿童患者（26例非PI对15例PI）中，95%（39/41）没有深静脉血栓形成的迹象或病史。这三种评分系统在预测儿童PE或PI方面表现不佳。名义上与PI相关的特征包括胸膜积液、最高体温、淋巴细胞比、胸痛、血尿素氮（BUN）、中性粒细胞比、最大d -二聚体、白细胞计数和中性粒细胞计数。结论：原位肺动脉血栓形成是儿科PE的主要形式。胸痛、BUN和最高体温被确定为PI发生的独立危险因素。逻辑回归模型显示了良好的疗效，可以作为未来发展的PI评分系统的工具。

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