Fibrinolytic phenotyping offers a conceptual framework to explain variable thrombotic and bleeding risk in anticoagulated older adults but lacks validated thresholds, standardization, and prospective outcome data, precluding routine clinical use at present.
Si bien la hipofibrinolisis relacionada con la edad proporciona una justificación biológica para los riesgos trombóticos y hemorrágicos residuales en adultos mayores anticoagulados, la fenotipificación fibrinolítica sigue siendo una herramienta de investigación aún no lista para la práctica clínica rutinaria.
Abstract 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.
Besenyei et al. (Fri,) realizaron una revisión en adultos mayores que reciben anticoagulación a largo plazo por condiciones como fibrilación auricular y tromboembolismo venoso. Se evaluaron la fenotipificación fibrinolítica y la evaluación frente a la estratificación de riesgo clínico estándar y la anticoagulación guiada sin fenotipificación fibrinolítica sobre la asociación de los fenotipos fibrinolíticos con los resultados trombóticos y hemorrágicos en adultos mayores anticoagulados. La fenotipificación fibrinolítica ofrece un marco conceptual para explicar el riesgo variable de trombosis y hemorragia en adultos mayores anticoagulados pero carece de umbrales validados, estandarización y datos de resultados prospectivos, lo que impide su uso clínico rutinario en la actualidad.