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.
While age-related hypofibrinolysis provides a biological rationale for residual thrombotic and bleeding risks in anticoagulated older adults, fibrinolytic phenotyping remains a research tool not yet ready for routine clinical practice.
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,) conducted a review in Older adults receiving long-term anticoagulation for conditions such as atrial fibrillation and venous thromboembolism. Fibrinolytic phenotyping and assessment vs. Standard clinical risk stratification and guideline-directed anticoagulation without fibrinolytic phenotyping was evaluated on Association of fibrinolytic phenotypes with thrombotic and bleeding outcomes in anticoagulated older adults. 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.