血栓性疾病生物标志物研究进展

Research Progress on Biomarkers for Thrombotic Diseases

摘要: 血栓性疾病是全球死亡和残疾的主要原因之一，早期诊断与精准治疗面临重大挑战。随着血栓形成机制研究的深入，生物标志物已从单一指标发展为覆盖多个病理生理环节的网络。本文围绕血栓形成的核心病理生理环节，从内皮损伤与功能障碍、高凝状态与凝血活化、炎症免疫与血小板活化以及纤溶功能失调四个维度，系统整合各类生物标志物的研究进展与临床价值。传统标志物中，D-二聚体具有高阴性预测值但特异性低，年龄校正及联合纤维蛋白原可部分提高效能；凝血因子VIII及THBD基因多态性为静脉血栓栓塞症(VTE)风险提供遗传信息。新型血栓四项(TAT、PIC、TM、t-PAIC)直接反映凝血酶生成、纤溶活化及内皮损伤，诊断效能显著优于传统指标，在肿瘤相关VTE、术后VTE及特殊人群风险评估中展现出独特价值。此外，中性粒细胞胞外诱捕网(NETs)、P-选择素、微小RNA及血小板–炎症相关标志物等新兴分子为血栓机制研究与液体活检提供了新视角。特殊人群(恶性肿瘤、手术创伤、孕产妇及老年患者)的风险评估模型联合分子标志物可显著提高预测准确性。本文进一步设立独立章节，系统剖析主要新兴标志物在分析前、分析中、分析后全链条面临的标准化挑战，并探讨从研究发现到进入临床指南所需跨越的循证阶梯，为转化研究提供现实指导框架。当前研究仍面临样本量不足、缺乏外部验证、机制不清及干预证据匮乏等局限。未来应聚焦大规模多中心前瞻性验证、新型标志物开发、多组学联合建模及标志物指导的个体化干预临床试验，以推动血栓性疾病诊疗水平的全面提升。

Abstract: Thrombotic diseases are a leading cause of global mortality and disability, posing significant challenges in early diagnosis and precise treatment. With advancements in thrombosis mechanisms, biomarkers have evolved from single indicators to networks covering multiple pathophysiological processes. This article systematically integrates research progress and clinical value of various biomarkers around the core pathophysiological mechanisms of thrombosis, focusing on four dimensions: endothelial injury and dysfunction, hypercoagulability and coagulation activation, inflammatory immunity and platelet activation, and fibrinolytic dysfunction. Among traditional biomarkers, D-dimer exhibits high negative predictive value but low specificity, while age correction and combined fibrinogen measurements can partially enhance efficacy. Coagulation factor VIII and THBD gene polymorphisms provide genetic information for venous thromboembolism (VTE) risk assessment. Novel thrombosis quartet markers (TAT, PIC, TM, t-PAIC) directly reflect thrombin generation, fibrinolysis activation, and endothelial injury, demonstrating significantly superior diagnostic performance to traditional indicators. These markers exhibit unique value in tumor-associated VTE, postoperative VTE, and risk assessment for special populations. Additionally, emerging molecules such as neutrophil extracellular traps (NETs), P-selectin, microRNAs, and platelet-inflammatory-related biomarkers offer new perspectives for thrombosis mechanism research and liquid biopsy. Risk assessment models for special populations (malignant tumors, surgical trauma, pregnant women, and elderly patients) significantly improve predictive accuracy when combined with molecular biomarkers. This article further establishes dedicated sections to systematically analyze standardization challenges faced by major emerging biomarkers across pre-analytical, analytical, and post-analytical stages, and explores the evidence-based steps required from research discovery to clinical guideline integration, providing a practical framework for translational research. Current studies still face limitations such as insufficient sample size, lack of external validation, unclear mechanisms, and scarce intervention evidence. Future efforts should focus on large-scale multicenter prospective validation, development of novel biomarkers, multi-omics joint modeling, and biomarker-guided individualized intervention clinical trials to comprehensively enhance the diagnosis and treatment of thrombotic diseases.