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<p>Age-related alterations of the haemostatic system substantially contribute to the heightened thrombotic and bleeding risk observed in older adults. While age-associated changes in coagulation have been extensively characterised, impairment of fibrinolysis remains comparatively underexplored, particularly in the context of anticoagulation management. Ageing promotes a hypofibrinolytic milieu through endothelial dysfunction, chronic low-grade inflammation, cellular senescence, and structural alterations of fibrin, resulting in reduced clot susceptibility to lysis. This narrative review synthesises current evidence on the biological mechanisms underlying age-related fibrinolytic suppression, critically evaluates available methods for functional fibrinolytic assessment, and discusses their potential clinical relevance in anticoagulated older adults. Throughout the manuscript, we explicitly distinguish between findings supported by clinical data in older populations, evidence extrapolated from non-geriatric or preclinical studies, and hypothesis-generating concepts. Although fibrinolytic phenotyping represents a compelling framework to explain thrombotic and bleeding events occurring despite guideline-concordant anticoagulation, its clinical implementation is currently constrained by limited assay standardisation, absence of validated thresholds, and lack of outcome-driven studies in geriatric populations. At present, fibrinolytic phenotyping should be regarded as a translational research tool rather than a basis for routine clinical decision-making. Prospective studies are required to determine whether phenotype-guided anticoagulation strategies can improve outcomes in older adults.</p> Graphical Abstract <p>&#xa0;Mechanisms, modifiers, and clinical framework of fibrinolytic ageing. Graphical overview summarising the biological mechanisms, lifestyle and metabolic modifiers, and conceptual clinical implications of age-related changes in fibrinolysis. The graphical abstract highlights key processes contributing to hypofibrinolysis in older adults and illustrates their potential relevance for thrombotic and bleeding susceptibility without implying clinical decision-making or therapeutic guidance.</p> <p></p>

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Functional fibrinolysis in older adults: clinical relevance and implications for personalised anticoagulation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月20日

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  • Attila Besenyei,
  • Zoltán Vajda,
  • Gyula Domján,
  • Dorina Markovics,
  • Andrea Virág,
  • Klára Gadó

摘要

Age-related alterations of the haemostatic system substantially contribute to the heightened thrombotic and bleeding risk observed in older adults. While age-associated changes in coagulation have been extensively characterised, impairment of fibrinolysis remains comparatively underexplored, particularly in the context of anticoagulation management. Ageing promotes a hypofibrinolytic milieu through endothelial dysfunction, chronic low-grade inflammation, cellular senescence, and structural alterations of fibrin, resulting in reduced clot susceptibility to lysis. This narrative review synthesises current evidence on the biological mechanisms underlying age-related fibrinolytic suppression, critically evaluates available methods for functional fibrinolytic assessment, and discusses their potential clinical relevance in anticoagulated older adults. Throughout the manuscript, we explicitly distinguish between findings supported by clinical data in older populations, evidence extrapolated from non-geriatric or preclinical studies, and hypothesis-generating concepts. Although fibrinolytic phenotyping represents a compelling framework to explain thrombotic and bleeding events occurring despite guideline-concordant anticoagulation, its clinical implementation is currently constrained by limited assay standardisation, absence of validated thresholds, and lack of outcome-driven studies in geriatric populations. At present, fibrinolytic phenotyping should be regarded as a translational research tool rather than a basis for routine clinical decision-making. Prospective studies are required to determine whether phenotype-guided anticoagulation strategies can improve outcomes in older adults.

Graphical Abstract

 Mechanisms, modifiers, and clinical framework of fibrinolytic ageing. Graphical overview summarising the biological mechanisms, lifestyle and metabolic modifiers, and conceptual clinical implications of age-related changes in fibrinolysis. The graphical abstract highlights key processes contributing to hypofibrinolysis in older adults and illustrates their potential relevance for thrombotic and bleeding susceptibility without implying clinical decision-making or therapeutic guidance.